FEATURE_phases list | FEATURE_enrollmentCount int64 | FEATURE_allocation string | FEATURE_interventionModel string | FEATURE_primaryPurpose class label | FEATURE_masking class label | FEATURE_healthyVolunteers bool | FEATURE_sex class label | FEATURE_oversightHasDmc bool | FEATURE_briefSummary string | FEATURE_detailedDescription string | FEATURE_conditions string | FEATURE_conditionsKeywords string | FEATURE_protocolPdfText string | FEATURE_numArms int64 | FEATURE_armDescriptions string | FEATURE_armGroupTypes list | FEATURE_numInterventions int64 | FEATURE_interventionTypes list | FEATURE_interventionDescriptions string | FEATURE_interventionNames string | FEATURE_numLocations int64 | FEATURE_locationDetails string | LABEL_ct_level_ade_population int64 | LABEL_sum_dosing_errors int64 | LABEL_dosing_error_rate float32 | LABEL_wilson_label int64 | METADATA_nctId string | METADATA_overallStatus class label | METADATA_completionDate date32 | METADATA_startDate date32 | METADATA_leadSponsorName string | METADATA_leadSponsorClass class label | METADATA_hasProtocol bool | METADATA_hasSap bool | METADATA_hasIcf bool | METADATA_protocolPdfLinks string | METADATA_count_Accidental drug intake by child int64 | METADATA_count_Accidental overdose int64 | METADATA_count_Accidental overdose (therapeutic agent) int64 | METADATA_count_Accidental underdose int64 | METADATA_count_Deliberate overdose int64 | METADATA_count_Dose calculation error int64 | METADATA_count_Drug administration error int64 | METADATA_count_Drug overdose int64 | METADATA_count_Drug overdose accidental int64 | METADATA_count_Extra dose administered int64 | METADATA_count_Incorrect dosage administered int64 | METADATA_count_Incorrect dose administered int64 | METADATA_count_Incorrect drug administration duration int64 | METADATA_count_Incorrect drug administration rate int64 | METADATA_count_Incorrect product administration duration int64 | METADATA_count_Intentional overdose int64 | METADATA_count_Medication error int64 | METADATA_count_Medication monitoring error int64 | METADATA_count_Multiple drug overdose int64 | METADATA_count_Multiple drug overdose accidental int64 | METADATA_count_Multiple drug overdose intentional int64 | METADATA_count_Multiple use of single-use product int64 | METADATA_count_Non-accidental overdose int64 | METADATA_count_Overdose int64 | METADATA_count_Overdose NOS int64 | METADATA_count_Overmedication int64 | METADATA_count_Prescribed overdose int64 | METADATA_count_Treatment noncompliance int64 | METADATA_count_Underdose int64 | METADATA_count_Unintentional medical device removal int64 | METADATA_count_Unintentional medical device removal by patient int64 | METADATA_wilson_lower_bound float32 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
[
5
] | 30 | RANDOMIZED | PARALLEL | 0TREATMENT | 3TRIPLE | false | 0ALL | null | To determine if conversion to enteric coated MPA allows an escalated dose of mycophenolic acid (MPA) to be tolerated in patients experiencing gastrointestinal (GI) symptoms | null | Renal Transplantation | Renal Transplantation Immunosuppression Renal transplant recipients Gastrointestinal symptoms associated with MMF therapy | null | 2 | arm 1: Equimolar dose of enteric-coated mycophenolate acid with mycophenolate mofetil placebo. 1000 mg mycophenolate mofetil = 720 mg enteric-coated mycophenolate acid (MPA equivalent dose). The active and placebo study medications were dispensed in separate bottles identified as Bottle A and Bottle B. arm 2: Mycophenolate mofetil therapy with placebo enteric-coated mycophenolate acid. The active and placebo study medications were dispensed in separate bottles identified as Bottle A and Bottle B. | [
0,
1
] | 4 | [
0,
0,
0,
0
] | intervention 1: None intervention 2: None intervention 3: None intervention 4: None | intervention 1: Enteric-coated Mycophenolate Acid (EC-MPA) intervention 2: Mycophenolate Mofetil (MMF) intervention 3: Placebo MMF intervention 4: Placebo EC-MPA | 37 | Phoenix | Arizona | United States | -112.07404 | 33.44838
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Orange | California | United States | -117.85311 | 33.78779
San Diego | California | United States | -117.16472 | 32.71571
San Francisco | California | United States | -122.41942 | 37.77493
Aurora | Colorado | United States | -104.83192 | 39.72943
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Orlando | Florida | United States | -81.37924 | 28.53834
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Portland | Maine | United States | -70.2589 | 43.65737
Baltimore | Maryland | United States | -76.61219 | 39.29038
Boston | Massachusetts | United States | -71.05977 | 42.35843
Boston | Massachusetts | United States | -71.05977 | 42.35843
Springfield | Massachusetts | United States | -72.58981 | 42.10148
Detroit | Michigan | United States | -83.04575 | 42.33143
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Durham | North Carolina | United States | -78.89862 | 35.99403
Greenville | North Carolina | United States | -77.36635 | 35.61266
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Fargo | North Dakota | United States | -96.7898 | 46.87719
Cleveland | Ohio | United States | -81.69541 | 41.4995
Portland | Oregon | United States | -122.67621 | 45.52345
Portland | Oregon | United States | -122.67621 | 45.52345
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Providence | Rhode Island | United States | -71.41283 | 41.82399
Nashville | Tennessee | United States | -86.78444 | 36.16589
Dallas | Texas | United States | -96.80667 | 32.78306
Houston | Texas | United States | -95.36327 | 29.76328
Temple | Texas | United States | -97.34278 | 31.09823
Murray | Utah | United States | -111.88799 | 40.66689
Burlington | Vermont | United States | -73.21207 | 44.47588
Charlottesville | Virginia | United States | -78.47668 | 38.02931 | 30 | 0 | 0 | 0 | NCT00658333 | 6TERMINATED | 2009-03-01 | 2008-03-01 | Novartis Pharmaceuticals | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 502 | RANDOMIZED | PARALLEL | 4SUPPORTIVE_CARE | 2DOUBLE | false | 0ALL | true | RATIONALE: Darbepoetin alfa may cause the body to make more red blood cells. Red blood cells contain iron that is needed to carry oxygen to the tissues. It is not yet known whether giving darbepoetin alfa (DA) together with intravenous iron or oral iron is more effective than giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy.
PURPOSE: This randomized phase III trial is studying giving darbepoetin alfa together with iron to see how well it works compared with giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy in patients with cancer. | OBJECTIVES:
Primary
\* To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia.
Secondary
* To compare the effects of these regimens on the mean hemoglobin increment from baseline to weeks 7 and 16 in these patients.
* To compare the effects of these regimens on the percentage of patients maintaining an average hemoglobin level within the American Society of Hematology/American Society of Clinical Oncology (ASH/ASCO)and National Comprehensive Cancer Network(NCCN) guideline-based target hemoglobin range (11-13 g/dL), once achieving a hemoglobin of ≥ 11 g/dL from week 1 to week 16 in the absence of RBC transfusions in the preceding 28 days of the treatment period.
* To compare the effects of intravenously (IV) iron, oral iron, or placebo on the response to darbepoetin alfa, in terms of time to achieving hemoglobin levels of ≥ 11g/dL.
* To compare the effects of these regimens on the percentage of patients who require RBC transfusions and the total transfusion needs.
* To compare the effects of these regimens on the change in hemoglobin week by week.
* To compare the effects of these regimens on quality-of-life changes from baseline to weeks 7 and 16.
* To identify if patients with inflammation (as indicated by elevated C-reactive protein (CRP) and serum hepcidin levels or low soluble transferrin receptor (sTfR)/log ferritin ratios) respond differently to darbepoetin alfa and iron therapy than patients without inflammation.
OUTLINE: Patients are stratified according to severity of anemia (mild \[hemoglobin ≥ 9.5 g/dL\] vs severe \[hemoglobin \< 9.5 g/dL\]), treatment with a platinum-containing regimen (yes vs no), and gender. Patients are randomized to 1 of 3 treatment arms.
* Arm I: Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate complex IV over 90 minutes on day 1.
* Arm II: Patients receive darbepoetin alfa as in arm I and oral ferrous sulfate once daily on days 1-21.
* Arm III: Patients receive darbepoetin alfa as in arm I and oral placebo once daily on days 1-21.
In all arms, treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
Patients complete quality-of-life (QOL) questionnaires in weeks 1, 7, and 16. | Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific | unspecified adult solid tumor, protocol specific monoclonal gammopathy of undetermined significance extramedullary plasmacytoma isolated plasmacytoma of bone refractory multiple myeloma stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma primary systemic amyloidosis Waldenstrom macroglobulinemia post-transplant lymphoproliferative disorder stage I adult T-cell leukemia/lymphoma stage II adult T-cell leukemia/lymphoma stage III adult T-cell leukemia/lymphoma stage IV adult T-cell leukemia/lymphoma recurrent adult T-cell leukemia/lymphoma angioimmunoblastic T-cell lymphoma anaplastic large cell lymphoma stage I cutaneous T-cell non-Hodgkin lymphoma stage II cutaneous T-cell non-Hodgkin lymphoma stage III cutaneous T-cell non-Hodgkin lymphoma stage IV cutaneous T-cell non-Hodgkin lymphoma recurrent cutaneous T-cell non-Hodgkin lymphoma stage I mycosis fungoides/Sezary syndrome stage II mycosis fungoides/Sezary syndrome stage III mycosis fungoides/Sezary syndrome stage IV mycosis fungoides/Sezary syndrome recurrent mycosis fungoides/Sezary syndrome stage I adult Hodgkin lymphoma stage II adult Hodgkin lymphoma stage III adult Hodgkin lymphoma stage IV adult Hodgkin lymphoma recurrent adult Hodgkin lymphoma recurrent adult grade III lymphomatoid granulomatosis stage I adult Burkitt lymphoma stage III adult Burkitt lymphoma stage IV adult Burkitt lymphoma noncontiguous stage II adult Burkitt lymphoma noncontiguous stage II adult diffuse large cell lymphoma noncontiguous stage II adult diffuse mixed cell lymphoma noncontiguous stage II adult diffuse small cleaved cell lymphoma noncontiguous stage II adult immunoblastic large cell lymphoma noncontiguous stage II adult lymphoblastic lymphoma noncontiguous stage II grade 1 follicular lymphoma noncontiguous stage II grade 2 follicular lymphoma noncontiguous stage II grade 3 follicular lymphoma noncontiguous stage II mantle cell lymphoma noncontiguous stage II marginal zone lymphoma noncontiguous stage II small lymphocytic lymphoma contiguous stage II adult Burkitt lymphoma contiguous stage II adult diffuse large cell lymphoma contiguous stage II adult diffuse mixed cell lymphoma contiguous stage II adult diffuse small cleaved cell lymphoma contiguous stage II adult immunoblastic large cell lymphoma contiguous stage II adult lymphoblastic lymphoma contiguous stage II grade 1 follicular lymphoma contiguous stage II grade 2 follicular lymphoma contiguous stage II grade 3 follicular lymphoma contiguous stage II mantle cell lymphoma contiguous stage II marginal zone lymphoma contiguous stage II small lymphocytic lymphoma stage I adult diffuse large cell lymphoma stage I adult diffuse mixed cell lymphoma stage I adult diffuse small cleaved cell lymphoma stage III adult diffuse large cell lymphoma stage III adult diffuse mixed cell lymphoma stage III adult diffuse small cleaved cell lymphoma stage IV adult diffuse large cell lymphoma stage IV adult diffuse mixed cell lymphoma stage IV adult diffuse small cleaved cell lymphoma stage I adult immunoblastic large cell lymphoma stage III adult immunoblastic large cell lymphoma stage IV adult immunoblastic large cell lymphoma stage I adult lymphoblastic lymphoma stage III adult lymphoblastic lymphoma stage IV adult lymphoblastic lymphoma stage I grade 1 follicular lymphoma stage I grade 2 follicular lymphoma stage I grade 3 follicular lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma stage I mantle cell lymphoma stage I marginal zone lymphoma stage III mantle cell lymphoma stage III marginal zone lymphoma stage IV mantle cell lymphoma stage IV marginal zone lymphoma stage I small lymphocytic lymphoma stage III small lymphocytic lymphoma stage IV small lymphocytic lymphoma extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma recurrent adult Burkitt lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma adult acute lymphoblastic leukemia in remission recurrent adult acute lymphoblastic leukemia untreated adult acute lymphoblastic leukemia stage I chronic lymphocytic leukemia stage II chronic lymphocytic leukemia stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia refractory chronic lymphocytic leukemia refractory hairy cell leukemia progressive hairy cell leukemia, initial treatment prolymphocytic leukemia anemia T-cell large granular lymphocyte leukemia acute undifferentiated leukemia mast cell leukemia adult nasal type extranodal NK/T-cell lymphoma untreated hairy cell leukemia | null | 3 | arm 1: Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate complex IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity. arm 2: Patients receive darbepoetin alfa as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity. arm 3: Patients receive darbepoetin alfa as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity. | [
0,
0,
0
] | 4 | [
2,
7,
0,
10
] | intervention 1: Given by injection intervention 2: Given by mouth intervention 3: Given by IV intervention 4: Given by mouth | intervention 1: darbepoetin alfa intervention 2: ferrous sulfate intervention 3: sodium ferric gluconate complex in sucrose intervention 4: placebo | 2 | Scottsdale | Arizona | United States | -111.89903 | 33.50921
Rochester | Minnesota | United States | -92.4699 | 44.02163 | 490 | 0 | 0 | 0 | NCT00661999 | 1COMPLETED | 2009-03-01 | 2006-01-01 | Mayo Clinic | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 822 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | true | Saxagliptin is a new investigational medication being developed for treatment of type 2 diabetes. This study is designed to assess the efficacy and tolerability of saxagliptin in addition to metformin and compare to sitagliptin in addition with metformin. | null | Type 2 Diabetes | Type 2 diabetes metformin | null | 2 | arm 1: saxagliptin add-on to metformin arm 2: sitagliptin add-on to metformin | [
0,
1
] | 2 | [
0,
0
] | intervention 1: tablet, per oral, once daily intervention 2: capsule, per oral, once daily | intervention 1: saxagliptin intervention 2: sitagliptin | 87 | Buenos Aires | Buenos Aires | Argentina | N/A | N/A
Lanús | Buenos Aires | Argentina | -58.39132 | -34.70757
Mar del Plata | Buenos Aires | Argentina | -57.5562 | -38.00042
Santa Fe | Santa Fe Province | Argentina | -60.70868 | -31.64881
Caba | N/A | Argentina | N/A | N/A
Capital Federal | N/A | Argentina | N/A | N/A
Ciudad de Buenos Aires | N/A | Argentina | N/A | N/A
Córdoba | N/A | Argentina | -64.18853 | -31.40648
Rosario | N/A | Argentina | -60.63932 | -32.94682
Aalst | Belgium | Belgium | 4.0355 | 50.93604
Bonheiden | Belgium | Belgium | 4.54714 | 51.02261
Genk | Belgium | Belgium | 5.50082 | 50.965
Gozée | Belgium | Belgium | 4.35273 | 50.33461
Hasselt | Belgium | Belgium | 5.33781 | 50.93106
Liège | Belgium | Belgium | 5.56749 | 50.63373
Saint-Médard | Belgium | Belgium | 5.32795 | 49.81538
Sint-Gillis-Waas | Belgium | Belgium | 4.12374 | 51.21914
Tessenderlo | Belgium | Belgium | 5.08856 | 51.06513
Thuillies | Belgium | Belgium | 4.33269 | 50.29899
Bruges | N/A | Belgium | 3.22424 | 51.20892
Aalborg | N/A | Denmark | 9.9187 | 57.048
Aarhus | N/A | Denmark | 10.21076 | 56.15674
Christiansfeld | N/A | Denmark | 9.48701 | 55.35817
Farsø | N/A | Denmark | 9.33925 | 56.77276
Gentofte Municipality | N/A | Denmark | 12.54601 | 55.74903
Hobro | N/A | Denmark | 9.79029 | 56.64306
Kolding | N/A | Denmark | 9.47216 | 55.4904
Rødovre Municipality | N/A | Denmark | 12.45373 | 55.68062
Viborg | N/A | Denmark | 9.40201 | 56.45319
Angers | N/A | France | -0.55202 | 47.47156
Château-Gontier | N/A | France | -0.70512 | 47.82705
Corbeil-Essonnes | N/A | France | 2.48757 | 48.60603
La Seyne-sur-Mer | N/A | France | 5.87816 | 43.10322
Laval | N/A | France | -0.77019 | 48.07247
Le Lavandou | N/A | France | 6.366 | 43.137
Montrevault | N/A | France | -1.04579 | 47.26145
Saint-Cyr | N/A | France | 4.73045 | 45.25183
Tiercé | N/A | France | -0.46787 | 47.6157
Toulon | N/A | France | 5.92836 | 43.12442
Witry-lès-Reims | N/A | France | 4.11921 | 49.29162
Bergamo | BG | Italy | 9.66721 | 45.69601
Foggia | FG | Italy | 15.55188 | 41.45845
Chiavari | GE | Italy | 9.32241 | 44.31771
Genova | GE | Italy | 11.87211 | 45.21604
Rozzano | MI | Italy | 9.1559 | 45.38193
Olbia | OT | Italy | 9.49802 | 40.92337
Padua | PD | Italy | 11.88586 | 45.40797
Pordenone | PN | Italy | 12.66051 | 45.95689
Mercato San Severino | SA | Italy | 14.75369 | 40.78468
Siena | SI | Italy | 11.33064 | 43.31822
Mexico | D.f. | Mexico | -98.43784 | 18.88011
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
Monterrey | N/A | Mexico | -100.31721 | 25.68435
Ålesund | N/A | Norway | 6.15492 | 62.47225
Elverum | N/A | Norway | 11.56231 | 60.88191
Halden | N/A | Norway | 11.38754 | 59.12478
Hamar | N/A | Norway | 11.06798 | 60.7945
Lierskogen | N/A | Norway | 10.33084 | 59.81978
Lillehammer | N/A | Norway | 10.46628 | 61.11514
Oslo | N/A | Norway | 10.74609 | 59.91273
Sandvika | N/A | Norway | 13.59125 | 64.46377
Strømmen | N/A | Norway | 11.01009 | 59.95063
Svelvik | N/A | Norway | 10.40872 | 59.6137
Benoni | Gauteng | South Africa | 28.32078 | -26.18848
Johannesburg | Gauteng | South Africa | 28.04363 | -26.20227
Cape Town | South Africa | South Africa | 18.42322 | -33.92584
Durban | South Africa | South Africa | 31.0292 | -29.8579
Cape Town | Western Cape | South Africa | 18.42322 | -33.92584
Bloemfontein | N/A | South Africa | 26.214 | -29.12107
Durban | N/A | South Africa | 31.0292 | -29.8579
Johannesburg | N/A | South Africa | 28.04363 | -26.20227
Kwa Zulu Natal | N/A | South Africa | N/A | N/A
Pretoria | N/A | South Africa | 28.18783 | -25.74486
Borås | N/A | Sweden | 12.9401 | 57.72101
Degeberga | N/A | Sweden | 14.08333 | 55.83333
Finspång | N/A | Sweden | 15.76739 | 58.70578
Gothenburg | N/A | Sweden | 11.96679 | 57.70716
Jönköping | N/A | Sweden | 14.15618 | 57.78145
Ödeshög | N/A | Sweden | 14.65294 | 58.22949
Örebro | N/A | Sweden | 15.2066 | 59.27412
Piteå | N/A | Sweden | 21.47944 | 65.31717
Rättvik | N/A | Sweden | 15.11787 | 60.88632
Skanör | N/A | Sweden | 12.85 | 55.41667
Timrå | N/A | Sweden | 17.32613 | 62.48654
Trollhättan | N/A | Sweden | 12.28864 | 58.28365
Uddevalla | N/A | Sweden | 11.9424 | 58.34784
Umeå | N/A | Sweden | 20.25972 | 63.82842 | 801 | 0 | 0 | 0 | NCT00666458 | 1COMPLETED | 2009-03-01 | 2008-04-01 | AstraZeneca | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 750 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | false | The purpose of this study is to compare duloxetine with other antidepressants in the treatment of severe depression. | null | Depression | Severe Depressive Episode | null | 5 | arm 1: study drug arm 2: None arm 3: None arm 4: None arm 5: None | [
0,
1,
1,
1,
1
] | 5 | [
0,
0,
0,
0,
0
] | intervention 1: 30-120 milligrams (mgs) orally daily for 12 weeks intervention 2: 20-80 mgs orally daily for 12 weeks intervention 3: 20-40 mgs orally daily for 12 weeks intervention 4: 20-50 mgs orally daily for 12 weeks intervention 5: 50-200 mgs orally daily for 12 weeks | intervention 1: duloxetine intervention 2: fluoxetine intervention 3: citalopram intervention 4: paroxetine intervention 5: sertraline | 61 | Carson | California | United States | -118.28202 | 33.83141
Irvine | California | United States | -117.82311 | 33.66946
San Diego | California | United States | -117.16472 | 32.71571
Sherman Oaks | California | United States | -118.44925 | 34.15112
Torrance | California | United States | -118.34063 | 33.83585
Pueblo | Colorado | United States | -104.60914 | 38.25445
Clearwater | Florida | United States | -82.8001 | 27.96585
Coral Springs | Florida | United States | -80.2706 | 26.27119
Deerfield Beach | Florida | United States | -80.09977 | 26.31841
Fort Myers | Florida | United States | -81.84059 | 26.62168
Gainesville | Florida | United States | -82.32483 | 29.65163
Hialeah | Florida | United States | -80.27811 | 25.8576
Melbourne | Florida | United States | -80.60811 | 28.08363
Miami | Florida | United States | -80.19366 | 25.77427
Winter Park | Florida | United States | -81.33924 | 28.6
Atlanta | Georgia | United States | -84.38798 | 33.749
Joliet | Illinois | United States | -88.0834 | 41.52519
Oak Brook | Illinois | United States | -87.92895 | 41.83281
Park Ridge | Illinois | United States | -87.84062 | 42.01114
Greenwood | Indiana | United States | -86.10665 | 39.61366
Terre Haute | Indiana | United States | -87.41391 | 39.4667
Prairie Village | Kansas | United States | -94.63357 | 38.99167
Wichita | Kansas | United States | -97.33754 | 37.69224
Gaithersburg | Maryland | United States | -77.20137 | 39.14344
Glen Burnie | Maryland | United States | -76.62469 | 39.16261
Rockville | Maryland | United States | -77.15276 | 39.084
Fall River | Massachusetts | United States | -71.15505 | 41.70149
St Louis | Missouri | United States | -90.19789 | 38.62727
Clementon | New Jersey | United States | -74.98294 | 39.8115
Princeton | New Jersey | United States | -74.65905 | 40.34872
Brooklyn | New York | United States | -73.94958 | 40.6501
Fresh Meadows | New York | United States | -73.79347 | 40.73482
Mount Kisco | New York | United States | -73.72708 | 41.20426
Rochester | New York | United States | -77.61556 | 43.15478
Staten Island | New York | United States | -74.13986 | 40.56233
Concord | North Carolina | United States | -80.58158 | 35.40888
Durham | North Carolina | United States | -78.89862 | 35.99403
Beachwood | Ohio | United States | -81.50873 | 41.4645
Dayton | Ohio | United States | -84.19161 | 39.75895
Kettering | Ohio | United States | -84.16883 | 39.6895
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Eugene | Oregon | United States | -123.08675 | 44.05207
Havertown | Pennsylvania | United States | -75.30852 | 39.98095
Media | Pennsylvania | United States | -75.38769 | 39.91678
Newtown | Pennsylvania | United States | -74.93683 | 40.22928
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Lincoln | Rhode Island | United States | -71.435 | 41.92111
Columbia | South Carolina | United States | -81.03481 | 34.00071
Sioux Falls | South Dakota | United States | -96.70033 | 43.54997
Austin | Texas | United States | -97.74306 | 30.26715
Dallas | Texas | United States | -96.80667 | 32.78306
Friendswood | Texas | United States | -95.20104 | 29.5294
Houston | Texas | United States | -95.36327 | 29.76328
Lake Jackson | Texas | United States | -95.43439 | 29.03386
San Antonio | Texas | United States | -98.49363 | 29.42412
Wichita Falls | Texas | United States | -98.49339 | 33.91371
Woodstock | Vermont | United States | -72.51843 | 43.62424
Charlottesville | Virginia | United States | -78.47668 | 38.02931
Herndon | Virginia | United States | -77.3861 | 38.96955
Bellevue | Washington | United States | -122.20068 | 47.61038
Brown Deer | Wisconsin | United States | -87.96453 | 43.16334 | 750 | 0 | 0 | 0 | NCT00666757 | 1COMPLETED | 2009-03-01 | 2008-05-01 | Eli Lilly and Company | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 153 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | false | The purpose of this study was to investigate the initial dose and dose adjustment range for paricalcitol injection in patients with chronic kidney disease on hemodialysis who have secondary hyperparathyroidism. | This multicenter, randomized, open-label trial consisted of 4 dose-adjustment regimens for paricalcitol injection (initial doses and dose adjustment ranges were 2 ± 1 µg, 2 ± 2 µg, 4 ± 1 µg, and 4 ± 2 µg) and 1 maxacalcitol regimen (initial dose and dose adjustment range was 5 µg ± 2.5 µg or 10 µg ± 2.5 µg) as a reference group. Subjects who met the inclusion criteria were randomized equally to 1 of the treatment groups with iPTH values at screening (\< 500 pg/mL or ≥ 500 pg/mL) as a dynamic allocation factor. Study drugs were administered 3 times weekly (every other day) from the venous end of the hemodialysis circuit just before completion of the dialysis session. The initial doses were continued for 2 weeks, followed by dose adjustments (increase, maintenance, decrease, suspension, or resumption) by 1 µg or 2 µg units for the paricalcitol groups and by 2.5 µg units for the maxacalcitol group based on iPTH, calcium (adjusted), and phosphorus values every 2 weeks.
Subjects in the paricalcitol groups were to be suspended from treatment if their iPTH value decreased to \< 60 pg/mL in accordance with the guidelines proposed by the Japanese Society of Dialysis Therapy for the treatment of secondary hyperparathyroidism in chronic dialysis patients (control goal value of 60-180 pg/mL for iPTH). The dose adjustment criteria based on iPTH values for the maxacalcitol group were set according to the prescribing information for maxacalcitol (suspended when iPTH decreased to ≤ 150 pg/mL). | Chronic Kidney Disease on Hemodialysis Secondary Hyperparathyroidism | chronic kidney disease secondary hyperparathyroidism hemodialysis paricalcitol maxacalcitol | null | 5 | arm 1: Paricalcitol initial dosage 2 micrograms (µg) with incremental adjustment of 1 µg arm 2: Paricalcitol initial dosage 2 µg with incremental adjustment of 2 µg arm 3: Paricalcitol initial dosage 4 µg with incremental adjustment of 1 µg arm 4: Paricalcitol initial dosage 4 µg with incremental adjustment of 2 µg arm 5: Maxacalcitol initial dosage 5 or 10 µg with incremental adjustment of 2.5 µg | [
0,
0,
0,
0,
5
] | 2 | [
0,
0
] | intervention 1: Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks. intervention 2: Study drug was administered 3 times per week (no more frequently than every other day) intravenously immediately before the completion of hemodialysis. The initial dosage was administered for 2 weeks, with subsequent dosage adjustment based on the subject's iPTH, calcium (adjusted), and phosphorus levels every 2 weeks. Total duration of treatment was 12 weeks. | intervention 1: Maxacalcitol intervention 2: Paricalcitol | 12 | Tokyo | Metropolis | Japan | 139.69171 | 35.6895
Aichi | Prefecture | Japan | 130.62158 | 32.51879
Chiba | Prefecture | Japan | 140.11667 | 35.6
Fukuoka | Prefecture | Japan | 130.41667 | 33.6
Hokkaido | Prefecture | Japan | N/A | N/A
Ibaraki | Prefecture | Japan | 135.56828 | 34.81641
Kanagawa | Prefecture | Japan | 139.91667 | 37.58333
Kumamoto | Prefecture | Japan | 130.69181 | 32.80589
Nagano | Prefecture | Japan | 138.18333 | 36.65
Nagasaki | Prefecture | Japan | 129.88333 | 32.75
Osaka | Prefecture | Japan | 135.50107 | 34.69379
Saitama | Prefecture | Japan | 139.65657 | 35.90807 | 153 | 0 | 0 | 0 | NCT00667576 | 1COMPLETED | 2009-03-01 | 2008-04-01 | Abbott | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 830 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | false | The purpose of this study is to determine if two sustained released formulations of carisoprodol are more effective than placebo. | Methodology:
This will be a randomized, double-blind, double-dummy, placebo-controlled, parallel-group study in subjects 18-70 years of age with acute, painful, muscle spasm of the lower back. The study consists of a baseline screening (Study Day 1), during which subjects will be evaluated for inclusion/exclusion criteria, and a 7-day double-blind treatment period (Study Day 1 through Study Day 7). Subjects will be randomly assigned to be dosed twice daily with one of the following double-blind treatments: SR carisoprodol 500-mg tablets, SR carisoprodol 700-mg tablets, or placebo.
Subjects will be evaluated in the clinic on Study Days 1, 3 and 7. Subjects who remain symptomatic on Study Day 7 will be allowed to continue in the study for a 7-day, double-blind extension period at the discretion of the Investigator. Subjects will be contacted by telephone for a safety follow-up 7 days after the last dose of study medication.
A pharmacokinetic (PK) substudy will be conducted at selected sites. These sites will obtain blood samples for PK analysis at the end of the 7-day treatment period and the 14-day treatment period, if applicable. | Lower Back Pain | null | 3 | arm 1: Carisoprodol 700 mg twice daily arm 2: Carisoprodol SR 500 mg twice daily arm 3: Placebo | [
0,
0,
2
] | 3 | [
0,
0,
0
] | intervention 1: 700 mg twice daily tablet intervention 2: carisoprodol SR 500 mg tablet intervention 3: placebo tablet | intervention 1: Carisoprodol SR 700 mg intervention 2: Carisoprodol SR 500 mg intervention 3: Placebo | 73 | Birmingham | Alabama | United States | -86.80249 | 33.52066
Gulf Shores | Alabama | United States | -87.70082 | 30.24604
Hueytown | Alabama | United States | -86.99666 | 33.45122
Montgomery | Alabama | United States | -86.29997 | 32.36681
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Tempe | Arizona | United States | -111.90931 | 33.41477
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Anaheim | California | United States | -117.9145 | 33.83529
Beverly Hills | California | United States | -118.40036 | 34.07362
Burbank | California | United States | -118.30897 | 34.18084
Inglewood | California | United States | -118.35313 | 33.96168
Los Angeles | California | United States | -118.24368 | 34.05223
Newport Beach | California | United States | -117.92895 | 33.61891
San Diego | California | United States | -117.16472 | 32.71571
Santa Ana | California | United States | -117.86783 | 33.74557
Santa Barbara | California | United States | -119.69819 | 34.42083
Colorado Springs | Colorado | United States | -104.82136 | 38.83388
Denver | Colorado | United States | -104.9847 | 39.73915
Clearwater | Florida | United States | -82.8001 | 27.96585
Daytona Beach | Florida | United States | -81.02283 | 29.21081
Gainesville | Florida | United States | -82.32483 | 29.65163
Hollywood | Florida | United States | -80.14949 | 26.0112
Kissimmee | Florida | United States | -81.41667 | 28.30468
Lakeland | Florida | United States | -81.9498 | 28.03947
Largo | Florida | United States | -82.78842 | 27.90979
Melbourne | Florida | United States | -80.60811 | 28.08363
Naranja | Florida | United States | -80.42283 | 25.51816
Pembroke Pines | Florida | United States | -80.22394 | 26.00315
Saint Cloud | Florida | United States | -81.28118 | 28.2489
Tampa | Florida | United States | -82.45843 | 27.94752
Tampa | Florida | United States | -82.45843 | 27.94752
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Atlanta | Georgia | United States | -84.38798 | 33.749
Atlanta | Georgia | United States | -84.38798 | 33.749
Decatur | Georgia | United States | -84.29631 | 33.77483
Naperville | Illinois | United States | -88.14729 | 41.78586
Wichita | Kansas | United States | -97.33754 | 37.69224
Lexington | Kentucky | United States | -84.47772 | 37.98869
Lexington | Kentucky | United States | -84.47772 | 37.98869
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Waterford | Michigan | United States | -83.41181 | 42.69303
Jackson | Mississippi | United States | -90.18481 | 32.29876
Omaha | Nebraska | United States | -95.94043 | 41.25626
Omaha | Nebraska | United States | -95.94043 | 41.25626
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Bloomfield | New Jersey | United States | -74.18542 | 40.80677
West Caldwell | New Jersey | United States | -74.29695 | 40.84852
New York | New York | United States | -74.00597 | 40.71427
Fargo | North Dakota | United States | -96.7898 | 46.87719
Columbus | Ohio | United States | -82.99879 | 39.96118
Dayton | Ohio | United States | -84.19161 | 39.75895
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Harleysville | Pennsylvania | United States | -75.38712 | 40.27955
Warminster | Pennsylvania | United States | -75.09962 | 40.20678
Greer | South Carolina | United States | -82.22706 | 34.93873
Pelzer | South Carolina | United States | -82.45596 | 34.64234
Kingsport | Tennessee | United States | -82.56182 | 36.54843
Arlington | Texas | United States | -97.10807 | 32.73569
Austin | Texas | United States | -97.74306 | 30.26715
Bryan | Texas | United States | -96.36996 | 30.67436
Colleyville | Texas | United States | -97.15501 | 32.88096
Dallas | Texas | United States | -96.80667 | 32.78306
Georgetown | Texas | United States | -97.67723 | 30.63269
Houston | Texas | United States | -95.36327 | 29.76328
New Braunfels | Texas | United States | -98.12445 | 29.703
San Antonio | Texas | United States | -98.49363 | 29.42412
San Antonio | Texas | United States | -98.49363 | 29.42412
San Antonio | Texas | United States | -98.49363 | 29.42412
Sugar Land | Texas | United States | -95.63495 | 29.61968
Weber City | Virginia | United States | -78.28389 | 37.75514 | 830 | 0 | 0 | 0 | NCT00671879 | 1COMPLETED | 2009-03-01 | 2008-04-01 | Meda Pharmaceuticals | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
3
] | 94 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | null | This study investigates whether symptom-limited exercise capacity in ischemic cardiomyopathy patients with angina is deleteriously affected by treatment with CK-1827452. | The primary objective of this study is to assess the effect of intravenous (i.v.) CK-1827452 on symptom-limited exercise tolerance in patients with ischemic cardiomyopathy and angina. The secondary objectives are to assess the tolerability of CK-1827452 administered three times daily (tid) to steady state in an immediate-release (IR), blend-in-capsule oral formulation to outpatients with ischemic cardiomyopathy and angina and to assess CK-1827452 plasma concentrations at trough and 1 hour after dosing with CK-1827452 administered tid to steady state in an IR, blend-in-capsule oral formulation to outpatients with ischemic cardiomyopathy and angina. | Heart Failure Myocardial Ischemia Angina Pectoris | null | 2 | arm 1: CK-1827452 I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr or placebo, followed by 6 days three times a day oral dose and a final single oral dose arm 2: CK-1827452 I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr or placebo, followed by 6 days three times a day oral dose and a final single oral dose | [
0,
0
] | 6 | [
0,
0,
0,
0,
0,
0
] | intervention 1: I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr intervention 2: 12.5mg oral immediate release capsule intervention 3: I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr intervention 4: 25mg oral immediate release capsule intervention 5: Matching placebo iv infusion intervention 6: Matching placebo oral immediate release capsule | intervention 1: CK-1827452 24mg and 6 mg iv infusion intervention 2: CK-1827452 12.5mg capsule intervention 3: CK-1827452 48 mg and 11 mg iv infusion intervention 4: CK-1827452 25mg capsule intervention 5: Placebo iv infusion intervention 6: Placebo capsule | 14 | Tbilisi | N/A | Georgia | 44.83412 | 41.69143
Tbilisi | N/A | Georgia | 44.83412 | 41.69143
Tbilisi | N/A | Georgia | 44.83412 | 41.69143
Tbilisi | N/A | Georgia | 44.83412 | 41.69143
Tbilisi | N/A | Georgia | 44.83412 | 41.69143
Tbilisi | N/A | Georgia | 44.83412 | 41.69143
Barnaul | N/A | Russia | 83.7456 | 53.3598
Barnaul | N/A | Russia | 83.7456 | 53.3598
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Volgograd | N/A | Russia | 44.50183 | 48.71939 | 188 | 0 | 0 | 0 | NCT00682565 | 1COMPLETED | 2009-03-01 | 2008-04-01 | Cytokinetics | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
3
] | 29 | RANDOMIZED | PARALLEL | 0TREATMENT | 1SINGLE | false | 0ALL | false | The objective of this clinical study is to examine the safety and effectiveness of intravenous MN-221 compared to placebo when administered as an adjunct to standard therapy in subjects experiencing an acute exacerbation of asthma. | This is a randomized, modified single-blind, placebo-controlled dose escalation, multi-center Emergency Department (ED) study. Each subject will receive MN-221 or placebo administered through a continuous intravenous infusion in addition to the standardized care treatment for an acute exacerbation of asthma. The study is a modified single-blind design where the subject and the Investigator will be blinded.
Upon presentation to the ED for assessment and treatment for an acute exacerbation of asthma the subject should receive standardized care consistent with the National Asthma Education and Prevention Program (NAEPP) guidelines.
Once the subject has received the standardized initial treatment regimen and has been assessed for response to that treatment (signs and symptoms of acute asthma exacerbation), an informed consent to participate in the study will be obtained, study entry criteria will be reviewed, a 12-lead ECG will be performed, a dyspnea index scale assessment will be conducted, and spirometry will be performed. If the subject's FEV1 is ≤ 55% of predicted and the subject meets all other study entry criteria the subject will be randomized to receive either MN-221 or placebo. Throughout the screening process the subject will continue to receive the appropriate medical care consistent with the NAEPP guidelines for the treatment of acute exacerbations of asthma.
There will be up to three dose groups with generally twelve subjects in each group. Subjects enrolled in the study will receive an intravenous infusion of MN-221 study drug or placebo. Generally six subjects will be randomized to receive MN-221 and generally six subjects will be randomized to receive placebo in each dose group.
The initial dose group will be randomized to receive:
* 16 μg/min of MN-221 for 15 minutes (total dose of 240 μg) or placebo.
Subsequent dose groups will receive the following proposed doses:
* 30 μg/min for 15 minutes (total dose of 450 μg) or placebo, and
* 16 μg/min for 15 minutes followed by 8 μg/min for 105 minutes (total dose of 1,080 μg) or placebo.
During the study treatment period, the subject will continue to receive the following standard treatment and assessment until the subject's FEV1 reaches ≥ 70% of predicted:
* Assessment of subject's signs and symptoms;
* Complete a dyspnea index scale;
* Supplemental oxygen to maintain oxygen saturation as measured by pulse oximetry of ≥ 90%;
* Albuterol (2.5 mg) via nebulizer given hourly; NOTE: Albuterol (2.5 mg) via nebulizer may be given up to every 20 minutes if deemed to be indicated by the Investigator.
* Ipratropium (0.5 mg) via nebulizer may be given every hour if deemed to be indicated by the Investigator.
* Spirometry completed within 10 minutes of nebulizer treatments; followed by,
* Reassessment of signs and symptoms. If the subject does not improve to FEV1 ≥ 70% of predicted during the study treatment period, the subject may continue to receive further treatment including hospital admission at the discretion of the Investigator. The study will be approximately 6.5 hours in length (Hour -1.5 to Hour 5) while the subject remains in the ED. Safety, efficacy and PK parameters will be monitored throughout the treatment period. An initial 24-hour post-randomization follow-up visit will be completed to evaluate the subject's health status as well as for safety and PK parameters. A second follow-up contact will be completed by telephone seven days post-randomization for safety purposes and to evaluate the subject's health status.
A risk/benefit evaluation will be performed by the study's Safety Review Committee at each dose level. The occurrence of clinical signs, symptoms, laboratory abnormalities, ECG abnormalities suggesting toxicity, or results of efficacy analyses (FEV1, dyspnea index scale), may result in a decision to modify the proposed planned dose escalations, to repeat a dose level, or to not evaluate any additional dose(s) of MN-221. | Asthma Status Asthmaticus | Asthma Dose-Escalation Controlled MN-221 | null | 2 | arm 1: MN-221 total dose of 240 mcg arm 2: i.v. infusion of MN-221 Placebo for 15 min | [
0,
2
] | 4 | [
0,
0,
0,
0
] | intervention 1: IV infusion of MN-221 16 mcg/min for 15 min; total dose of 240 mcg intervention 2: i.v. infusion of placebo for 15 minutes intervention 3: i.v. infusion of MN-221 30 mcg/min for 15 minutes (total dose of 450 mcg) intervention 4: i.v. infusion of MN-221 16 mcg/min for 15 minutes followed by 8 mcg/min for 105 minutes (total dose = 1,080 mcg) | intervention 1: Dose Group 1 intervention 2: MN-221 placebo intervention 3: Dose Group 2 intervention 4: Dose Group 3 | 9 | Phoenix | Arizona | United States | -112.07404 | 33.44838
Los Angeles | California | United States | -118.24368 | 34.05223
Sylmar | California | United States | -118.44925 | 34.30778
Detroit | Michigan | United States | -83.04575 | 42.33143
St Louis | Missouri | United States | -90.19789 | 38.62727
Brooklyn | New York | United States | -73.94958 | 40.6501
New Hyde Park | New York | United States | -73.68791 | 40.7351
Cleveland | Ohio | United States | -81.69541 | 41.4995
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238 | 29 | 0 | 0 | 0 | NCT00683449 | 6TERMINATED | 2009-03-01 | 2008-06-01 | MediciNova | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 481 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | false | This randomized, double-blind, placebo-controlled, multicenter, 8-week, clinical trial is designed to assess the efficacy and safety of vilazodone and to evaluate genetic biomarkers of treatment response associated with vilazodone use in adult patients diagnosed with MDD by the DSM-IV-TR criteria. | This randomized, double-blind, placebo-controlled, multicenter, 8-week, clinical trial is designed to assess the efficacy and safety of vilazodone and to evaluate genetic biomarkers of treatment response associated with vilazodone use in adult patients diagnosed with MDD by the DSM-IV-TR criteria. This study will enroll approximately 470 patients at approximately 10 clinical sites. Safety and efficacy will be assessed at each visit. A DNA sample will be collected and analyzed for response to vilazodone. | Major Depressive Disorder | null | 2 | arm 1: vilazodone arm 2: None | [
0,
2
] | 2 | [
0,
0
] | intervention 1: titration to 40 mg tablets qd (once a day) for 8 weeks intervention 2: placebo | intervention 1: vilazodone intervention 2: placebo | 9 | Newport Beach | California | United States | -117.92895 | 33.61891
Bradenton | Florida | United States | -82.57482 | 27.49893
Atlanta | Georgia | United States | -84.38798 | 33.749
Portland | Oregon | United States | -122.67621 | 45.52345
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Dallas | Texas | United States | -96.80667 | 32.78306
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Bellevue | Washington | United States | -122.20068 | 47.61038
Seattle | Washington | United States | -122.33207 | 47.60621 | 468 | 0 | 0 | 0 | NCT00683592 | 1COMPLETED | 2009-03-01 | 2008-03-01 | Forest Laboratories | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
3
] | 106 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | This study is designed to assess the effects of AZD 2624 in patients with schizophrenia | null | Schizophrenia | Schizophrenia | null | 3 | arm 1: AZD2624 40 mg arm 2: Olanzapine 15 mg arm 3: Matching Placebo | [
0,
5,
2
] | 3 | [
0,
0,
0
] | intervention 1: Oral Suspension intervention 2: PO BID intervention 3: None | intervention 1: AZD2624 intervention 2: Olanzapine intervention 3: Placebo | 1 | Rockville | Maryland | United States | -77.15276 | 39.084 | 106 | 0 | 0 | 0 | NCT00686998 | 1COMPLETED | 2009-03-01 | 2008-05-01 | AstraZeneca | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 19 | RANDOMIZED | CROSSOVER | 0TREATMENT | 2DOUBLE | false | 0ALL | false | Evaluation of treatment in participants with mild asthma. | To evaluate the effect of navarixin (MK-527123, SCH 527123) treatment on allergen-induced late asthmatic response (LAR) in participants with mild asthma. | Asthma | Neutrophilic Asthma | null | 2 | arm 1: Navarixin 30 mg capsule to be taken once daily in the morning for 10 days in Treatment Period 1, followed by a 2-4 week washout period, followed by matching placebo capsule to be taken once daily in the morning for 10 days in Treatment Period 2 arm 2: Matching placebo capsule to be taken once daily in the morning for 10 days in Treatment Period 1, followed by a 2-4 week washout period, followed by navarixin 30 mg capsule to be taken once daily in the morning for 10 days in Treatment Period 2 | [
0,
0
] | 2 | [
0,
0
] | intervention 1: 30 mg capsule to be taken once daily in the morning for 10 days during Treatment Period 1 or Treatment Period 2 intervention 2: Matching capsule to be taken once daily in the morning for 10 days during Treatment Period 1 or Treatment Period 2 | intervention 1: Navarixin intervention 2: Placebo | 0 | null | 33 | 0 | 0 | 0 | NCT00688467 | 1COMPLETED | 2009-03-01 | 2008-06-01 | Merck Sharp & Dohme LLC | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 31 | RANDOMIZED | CROSSOVER | 0TREATMENT | 0NONE | true | 0ALL | false | This is a prospective, placebo-controlled, cross-over trial comparing the the effects of approximately 7 weeks of placebo treatment to 7 weeks of ezetimibe (10mg/day) treatment on several parameters of reverse cholesterol transport (RCT) in men and post-menopausal women diagnosed with hypercholesterolemia. The primary hypothesis is that the ezetimibe treatment will increase the excretion of endogenous (plasma-derived) cholesterol as fecal sterols, with secondary hypotheses that there will be a significant increase in de novo cholesterol synthesis, treatment will increase cholesterol efflux from tissues into the bloodstream, and increase global RCT. | The study will compare the effects of approximately 7 weeks of placebo treatment to 7 weeks of ezetimibe (10mg/day) on: 1) the efficiency of endogenous (plasma-derived) cholesterol excretion (%/day) 2) de novo cholesterol (DNC) synthesis ((%/day) 3) cholesterol efflux from tissues into blood (Ra), and 4) global RCT (efflux from tissues that is excreted as fecal sterols). Subjects will receive 7 weeks of either treatment or placebo, undergo RCT and DNC measurements, taking 10 days, then cross-over to the alternate placebo or treatment for an additional 7 weeks, followed by a second set of RCT and DNC measurements. | Hypercholesterolemia | metabolic diseases metabolic disorder dyslipidemias lipid metabolism disorders | null | 2 | arm 1: ezetimibe (10mg/day)for 7 weeks arm 2: Placebo control | [
0,
2
] | 2 | [
0,
0
] | intervention 1: 1 tablet,10mg, once a day, for 7 weeks intervention 2: 1 tablet, once a day, for 7 weeks | intervention 1: ezetimibe intervention 2: Placebo | 1 | Chicago | Illinois | United States | -87.65005 | 41.85003 | 62 | 0 | 0 | 0 | NCT00701727 | 1COMPLETED | 2009-03-01 | 2008-06-01 | Radiant Research | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 591 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | false | Benzoyl peroxide, clindamycin and tazarotene are known to be effective treatment alternative for acne vulgaris. The purpose of this study is to assess the safety and efficacy of a combination product including these actives for the treatment of acne vulgaris.
You may be suitable to take part in this study because you have acne vulgaris on your face. Acne vulgaris usually affects the face, but it can also affect the skin on the chest, arms, legs, and back. | The study subjects must have acne vulgaris and will apply study drug to their face for 12 weeks.
Study visits will occur at baseline (day 1) and at weeks 2, 4, 8, and 12. Subjects will be assessed at every visit to determine how the study drug is working. Safety will be assessed by evaluation of adverse events (AEs), vital signs, physical examinations, and withdrawals from the study. | Acne Vulgaris | Acne Acne Vulgaris Pimples | null | 6 | arm 1: Benzoyl peroxide/clindamycin gel + tazarotene cream arm 2: Benzoyl peroxide/clindamycin gel + vehicle cream arm 3: Benzoyl peroxide gel + tazarotene cream arm 4: Clindamycin gel + tazarotene cream arm 5: Vehicle gel+ tazarotene cream arm 6: Vehicle gel + vehicle cream | [
0,
1,
1,
1,
1,
2
] | 5 | [
0,
0,
0,
0,
0
] | intervention 1: 5% benzoyl peroxide in a gel applied topically once a day intervention 2: 1% clindamycin phosphate applied topically once a day intervention 3: 0.1 % tazarotene in a cream applied topically once a day intervention 4: Vehicle gel is an identical gel without the active ingredients intervention 5: Vehicle cream is an identical cream without the active ingredients | intervention 1: Benzoyl peroxide gel intervention 2: Clindamycin gel intervention 3: Tazarotene cream intervention 4: Vehicle gel intervention 5: Vehicle cream | 16 | Little Rock | Arkansas | United States | -92.28959 | 34.74648
Fremont | California | United States | -121.98857 | 37.54827
Sacramento | California | United States | -121.4944 | 38.58157
Boulder | Colorado | United States | -105.27055 | 40.01499
Coral Gables | Florida | United States | -80.26838 | 25.72149
Newnan | Georgia | United States | -84.79966 | 33.38067
Mitchellville | Maryland | United States | -76.808 | 38.92
Warren | Michigan | United States | -83.01304 | 42.49044
Chapel Hill | North Carolina | United States | -79.05584 | 35.9132
High Point | North Carolina | United States | -80.00532 | 35.95569
Hershey | Pennsylvania | United States | -76.65025 | 40.28592
Goodlettsville | Tennessee | United States | -86.71333 | 36.32311
Knoxville | Tennessee | United States | -83.92074 | 35.96064
Dallas | Texas | United States | -96.80667 | 32.78306
Houston | Texas | United States | -95.36327 | 29.76328
San Antonio | Texas | United States | -98.49363 | 29.42412 | 587 | 0 | 0 | 0 | NCT00713609 | 1COMPLETED | 2009-03-01 | 2008-06-01 | Stiefel, a GSK Company | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 88 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | true | 0ALL | null | The purpose of this study is to evaluate dosages of ARX-F01 (opioid pain medication) versus a placebo (or sugar pill) for the treatment of post-operative pain in subjects following abdominal surgery. We hypothesize that subjects receiving placebo will have poor pain relief and will drop out of the study sooner and more often than the ARX-F01 treated subjects. | null | Major Upper or Lower Abdominal Surgery | null | 3 | arm 1: Oral Sufentanil arm 2: Oral sufentanil arm 3: Oral dosage of placebo | [
0,
0,
2
] | 2 | [
0,
0
] | intervention 1: Oral dosage of sufentanil intervention 2: Oral dosage of placebo | intervention 1: Oral sufentanil intervention 2: Placebo | 1 | Durham | North Carolina | United States | -78.89862 | 35.99403 | 88 | 0 | 0 | 0 | NCT00718081 | 1COMPLETED | 2009-03-01 | 2008-08-01 | Talphera, Inc | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
3
] | 9 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | true | The primary purpose of this study is to determine the efficacy and safety of cobiprostone (at two dose levels) as compared to placebo for lowering portal hypertension. | null | Portal Hypertension | null | 3 | arm 1: Participants receive matching placebo capsules three times daily (TID) arm 2: Participants receive 12 mcg Cobiprostone TID arm 3: Participants receive 18 mcg Cobiprostone TID | [
2,
0,
0
] | 2 | [
0,
0
] | intervention 1: Matching placebo capsules for oral administration intervention 2: Cobiprostone capsules for oral administration | intervention 1: Placebo intervention 2: Cobiprostone | 1 | Dallas | Texas | United States | -96.80667 | 32.78306 | 0 | 0 | 0 | 0 | NCT00737594 | 6TERMINATED | 2009-03-01 | 2008-07-01 | Sucampo Pharma Americas, LLC | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
5
] | 332 | RANDOMIZED | PARALLEL | 0TREATMENT | 3TRIPLE | false | 0ALL | false | The purpose of the study is to evaluate the efficacy and safety of a fixed dose combination of aliskiren HCTZ versus amlodipine in African American patients with Stage 2 hypertension. | null | Hypertension | Hypertension African American aliskiren hydrochlorothiazide systolic blood pressure diastolic blood pressure amlodipine stage 2 | null | 2 | arm 1: None arm 2: None | [
0,
1
] | 2 | [
0,
0
] | intervention 1: Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks intervention 2: Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks | intervention 1: Aliskiren Hydrochlorothiazide (HCTZ): 8 weeks intervention 2: Amlodipine: 8 weeks | 1 | East Hanover | New Jersey | United States | -74.36487 | 40.8201 | 332 | 0 | 0 | 0 | NCT00739596 | 1COMPLETED | 2009-03-01 | 2008-07-01 | Novartis Pharmaceuticals | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2,
3
] | 12 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | true | 1FEMALE | false | To assess the retention and anti-viral activity (human immunodeficiency virus (HIV) and herpes simplex virus 2 (genital herpes, HSV-2) of SPL7013 in cervicovaginal samples taken up to 24 hours after administration of 3% SPL7013 in the vagina. There is no hypothesis for this study. | null | HIV Infections HSV-2 Genital Herpes | Prevention | null | 1 | arm 1: 3%w/w SPL7013 vaginal gel (VivaGel) | [
0
] | 1 | [
0
] | intervention 1: A single application of VivaGel applied to the vagina on five separate occasions, each occasion separated by a minimum of 5 days. | intervention 1: 3% SPL7013 Gel (VivaGel) | 1 | Melbourne | N/A | Australia | 144.96332 | -37.814 | 12 | 0 | 0 | 0 | NCT00740584 | 1COMPLETED | 2009-03-01 | 2008-08-01 | Starpharma Pty Ltd | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 20 | RANDOMIZED | CROSSOVER | 7BASIC_SCIENCE | 2DOUBLE | true | 0ALL | false | The objective of this study is to investigate the interaction between marijuana and quetiapine, with the goal of using this information to improve marijuana treatment outcome. | The purpose of this study is to determine if quetiapine decreases marijuana relapse in a controlled lab setting. For the purposes of this model, relapse is defined as a return to marijuana use after a period of abstinence. The study will utilize an inpatient/outpatient, counter-balanced design, with each participant maintained on placebo and quetiapine (200 mg/day) for 18 days. Participants will begin taking capsules as outpatients so that the dose can be incremented prior to the inpatient phase. While inpatient, participants will have the opportunity to self-administer placebo (0.0%) or active marijuana (6.2%) 6 times per day, depending on the study day. Our laboratory model, which has distinguished the effects of a range of medications on marijuana withdrawal and relapse, will provide important information on the effect of quetiapine as a potential short-term pharmacotherapy to facilitate abstinence in the initial stages of marijuana treatment. | Marijuana Smoking | quetiapine smoked marijuana marijuana use | null | 2 | arm 1: Quetiapine (200mg/day): Packaged medication in size 00 opaque capsules with riboflavin filler. Study capsules (200 mg) were administered 2 times per day ((1100 and 2300 hours).
Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use. arm 2: Marijuana: Participants each received a single marijuana cigarette (provided by the National Institute on Drug Abuse) at each smoking occasion. Marijuana cigarettes were stored frozen in an airtight container and humidified at room temperature for 24 h prior to use. | [
0,
2
] | 3 | [
0,
0,
0
] | intervention 1: 0,6.2% THC intervention 2: 200 mg/day intervention 3: None | intervention 1: Marijuana intervention 2: Quetiapine intervention 3: Placebo oral capsule | 1 | New York | New York | United States | -74.00597 | 40.71427 | 40 | 0 | 0 | 0 | NCT00743366 | 1COMPLETED | 2009-03-01 | 2008-08-01 | New York State Psychiatric Institute | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 2 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | This single arm study evaluated the bone marrow response, safety, and tolerability of 6 months treatment with Avastin (bevacizumab) monotherapy in patients with chronic lymphocytic leukemia. Patients received 8 cycles (21 days duration) of Avastin monotherapy (15mg/kg) with 6 months of follow-up. | null | Lymphocytic Leukemia, Chronic | null | 1 | arm 1: Participants received bevacizumab 15 mg/kg intravenously on Day 1 of each 3-week cycle for 8 cycles. | [
0
] | 1 | [
0
] | intervention 1: Bevacizumab was supplied as a sterile liquid in single-use vials. | intervention 1: Bevacizumab | 1 | Salzburg | N/A | Austria | 13.04399 | 47.79941 | 2 | 0 | 0 | 0 | NCT00754650 | 1COMPLETED | 2009-03-01 | 2008-09-01 | Hoffmann-La Roche | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
3
] | 74 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | The primary aim of this study is to investigate the tolerability and safety of AZD 1236 compared with placebo ("inactive substance") in COPD patients by assessment of Adverse Events, vital signs and laboratory safety assessments. | null | Chronic Obstructive Pulmonary Disease | COPD | null | 2 | arm 1: None arm 2: None | [
0,
2
] | 2 | [
0,
0
] | intervention 1: oral tablet, 75 mg, twice daily during 6 weeks intervention 2: Dosing to match AZD1236 | intervention 1: AZD1236 intervention 2: Placebo | 14 | Rousse | N/A | Bulgaria | 25.9534 | 43.84872
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Helsinki | N/A | Finland | 24.93545 | 60.16952
Oulu | N/A | Finland | 25.46816 | 65.01236
Preitilä | N/A | Finland | 22.73781 | 60.46203
Berlin | N/A | Germany | 13.41053 | 52.52437
Grobhansdorf | N/A | Germany | N/A | N/A
Győr | N/A | Hungary | 17.63512 | 47.68333
Komló | N/A | Hungary | 18.26494 | 46.19278
Pécs | N/A | Hungary | 18.23083 | 46.0725
Vásárosnamény | N/A | Hungary | 22.31325 | 48.12542
Bojnice | N/A | Slovakia | 18.5864 | 48.78511
Liptovský Hrádok | N/A | Slovakia | 19.72335 | 49.03962
Žilina | N/A | Slovakia | 18.73941 | 49.22315 | 74 | 0 | 0 | 0 | NCT00758459 | 1COMPLETED | 2009-03-01 | 2008-09-01 | AstraZeneca | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 554 | RANDOMIZED | PARALLEL | 0TREATMENT | 3TRIPLE | false | 0ALL | false | The purpose of the study is to evaluate the benefit of treatment with oral dose of Ibodutant (code: MEN 15596) on IBS symptoms and the safety and tolerability of this therapy. | Irritable Bowel Syndrome (IBS) is a functional disorder characterised by chronic or recurrent abdominal pain or discomfort associated with altered bowel habits. This trial aims to evaluate the efficacy of Ibodutant in improvement of IBS symptoms through a daily oral administration, testing three dosages or placebo in IBS patients for 4-weeks. In each patient, the experimental clinical phase encompasses a screening/ 2-week run-in period (no study medication), followed by a 4-weeks treatment period and a 2-weeks treatment withdrawal period, for total study duration of 8 weeks in each patient. | Irritable Bowel Syndrome | Irritable Bowel Syndrome Bowel disease | null | 4 | arm 1: None arm 2: None arm 3: None arm 4: None | [
0,
0,
0,
2
] | 4 | [
0,
0,
0,
0
] | intervention 1: Oral tablet, dose level 1 (10 mg), once daily intervention 2: Oral tablet, dose level 2 (30 mg), once daily intervention 3: Oral tablet, dose level 3 (60 mg), once daily intervention 4: Oral tablet matching the three dose levels of ibodutant, once daily | intervention 1: Ibodutant intervention 2: Ibodutant intervention 3: Ibodutant intervention 4: Placebo | 6 | Ballerup Municipality | N/A | Denmark | 12.36328 | 55.73165
Berlin | N/A | Germany | 13.41053 | 52.52437
Riga | N/A | Latvia | 24.10589 | 56.946
Moscow | N/A | Russia | 37.61556 | 55.75222
Dnipropetrovsk | N/A | Ukraine | 35.04066 | 48.46664
Birmingham | N/A | United Kingdom | -1.89983 | 52.48142 | 551 | 0 | 0 | 0 | NCT00761007 | 1COMPLETED | 2009-03-01 | 2008-07-01 | Menarini Group | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 308 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | false | The primary purpose of the study was to test the efficacy of 2 tablets (twice daily) of ABT-712, compared to placebo, administered over a 4-week period in participants with moderate to severe mechanical chronic low back pain (CLBP). | The study used a randomized withdrawal design with an open label (OL) period prior to a double-blind (DB) period. Participants who were receiving benefit and were tolerating ABT-712 during the OL period were randomized into the DB period. Study drug was given for a total of 8 weeks, which included up to 3 weeks in OL, up to 4 weeks in DB, and a 1-week DB taper. During the OL period, all participants took increasing doses of ABT-712 until they were taking 2 tablets, twice daily. During the DB period, participants in the ABT-712 group took 2 ABT-712 tablets, twice daily throughout the 4 weeks, while participants in the placebo group took 2 placebo tablets twice daily. | Chronic Low Back Pain | Effect on sleep interference by pain | null | 3 | arm 1: 2 ABT-712 extended-release tablets, twice daily, for up to 3 weeks (open-label period). arm 2: 2 ABT-712 extended-release tablets, twice daily, for 4 weeks (double-blind period). arm 3: 2 placebo tablets, twice daily, for 4 weeks (double-blind period). | [
0,
0,
2
] | 2 | [
0,
0
] | intervention 1: ABT-712 extended-release tablet intervention 2: Placebo tablet | intervention 1: ABT-712 intervention 2: Placebo | 32 | Tempe | Arizona | United States | -111.90931 | 33.41477
Tempe | Arizona | United States | -111.90931 | 33.41477
Tucson | Arizona | United States | -110.92648 | 32.22174
Anaheim | California | United States | -117.9145 | 33.83529
Lomita | California | United States | -118.31507 | 33.79224
Clearwater | Florida | United States | -82.8001 | 27.96585
DeLand | Florida | United States | -81.30312 | 29.02832
Oldsmar | Florida | United States | -82.6651 | 28.03418
Pembroke Pines | Florida | United States | -80.22394 | 26.00315
Plantation | Florida | United States | -80.23184 | 26.13421
Chicago | Illinois | United States | -87.65005 | 41.85003
Crestview Hills | Kentucky | United States | -84.58494 | 39.02728
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Brockton | Massachusetts | United States | -71.01838 | 42.08343
Fall River | Massachusetts | United States | -71.15505 | 41.70149
Wellesley Hills | Massachusetts | United States | -71.27867 | 42.30843
Omaha | Nebraska | United States | -95.94043 | 41.25626
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Kettering | Ohio | United States | -84.16883 | 39.6895
Marion | Ohio | United States | -83.12852 | 40.58867
Perrysburg | Ohio | United States | -83.62716 | 41.557
Dallas | Texas | United States | -96.80667 | 32.78306
El Paso | Texas | United States | -106.48693 | 31.75872
Fort Worth | Texas | United States | -97.32085 | 32.72541
Killeen | Texas | United States | -97.7278 | 31.11712
San Antonio | Texas | United States | -98.49363 | 29.42412
San Antonio | Texas | United States | -98.49363 | 29.42412
Roanoke | Virginia | United States | -79.94143 | 37.27097
Spokane | Washington | United States | -117.42908 | 47.65966 | 546 | 0 | 0 | 0 | NCT00761150 | 1COMPLETED | 2009-03-01 | 2008-09-01 | AbbVie (prior sponsor, Abbott) | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 88 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | null | This was a multicenter, randomized, vehicle-controlled, double-blind parallel group study to evaluate the efficacy and safety of CD 2027 Oily Spray applied twice daily for 8 weeks in participants with plaque-type psoriasis. | null | Psoriasis | psoriasis spray calcitriol | null | 2 | arm 1: None arm 2: None | [
0,
2
] | 2 | [
0,
0
] | intervention 1: Participants applied Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks. intervention 2: Participants applied placebo matched to Calcitriol 3 mcg/g spray topically to the affected areas twice daily for 8 weeks. | intervention 1: CD 2027 intervention 2: Calcitriol Vehicle | 6 | Fridley | Minnesota | United States | -93.26328 | 45.08608
Nashville | Tennessee | United States | -86.78444 | 36.16589
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Barrie | Ontario | Canada | -79.66634 | 44.40011
North Bay | Ontario | Canada | -79.46633 | 46.3168
Waterloo | Ontario | Canada | -80.51639 | 43.4668 | 88 | 0 | 0 | 0 | NCT00763555 | 1COMPLETED | 2009-03-01 | 2008-09-01 | Galderma R&D | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 190 | RANDOMIZED | CROSSOVER | 0TREATMENT | 2DOUBLE | false | 0ALL | false | The purpose of this study is to compare once and twice daily GW685698 in asthma | null | Asthma | null | 1 | arm 1: None | [
0
] | 1 | [
0
] | intervention 1: Inhaled Corticosteroid | intervention 1: GW685698X | 16 | Long Beach | California | United States | -118.18923 | 33.76696
Long Beach | California | United States | -118.18923 | 33.76696
Torrance | California | United States | -118.34063 | 33.83585
Cocoa | Florida | United States | -80.742 | 28.38612
Tallahassee | Florida | United States | -84.28073 | 30.43826
Bethesda | Maryland | United States | -77.10026 | 38.98067
Columbia | Missouri | United States | -92.33407 | 38.95171
Rolla | Missouri | United States | -91.77127 | 37.95143
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Canton | Ohio | United States | -81.37845 | 40.79895
Medford | Oregon | United States | -122.87559 | 42.32652
Orangeburg | South Carolina | United States | -80.85565 | 33.49182
Austin | Texas | United States | -97.74306 | 30.26715
Boerne | Texas | United States | -98.73197 | 29.79466
San Antonio | Texas | United States | -98.49363 | 29.42412
Waco | Texas | United States | -97.14667 | 31.54933 | 554 | 0 | 0 | 0 | NCT00766090 | 1COMPLETED | 2009-03-01 | 2008-10-01 | GlaxoSmithKline | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
2
] | 49 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | false | This study is being conducted to determine the safety, tolerability, and pharmacokinetics (PK) of three different doses of an investigational medication, EVP-6124, in individuals with mild to moderate Alzheimer's disease who are also taking an Alzheimer's medication (AChEI \[acetylcholinesterase inhibitor\]: either donepezil or rivastigmine). In addition, PK of AChEI medications will be assessed. Cognitive function will be evaluated on an exploratory basis. | This is a randomized, double-blind, placebo-controlled, Phase 1b safety study of three dose levels of EVP-6124 in subjects with mild or moderate Alzheimer's disease and who are taking an AChEI medication (donepezil or rivastigmine).
Study drug will be supplied as capsules and will be orally administered once daily for a total of 28 days. Eligible subjects will be admitted to an inpatient study unit on Day -2 (two days before the first dose of study drug is administered) and will remain confined to the inpatient study unit for a total of five days. Starting on Day 4, subjects will continue the study in the outpatient setting, with study visits on Days 7, 14, 21, and 28. Safety assessments, PK sampling, and cognitive testing will be performed inpatient and at each study visit. | Alzheimer's Disease Central Nervous System Diseases | Alzheimer's Disease Central Nervous System Diseases Pharmacokinetics Cognition | null | 4 | arm 1: None arm 2: None arm 3: None arm 4: None | [
0,
0,
0,
2
] | 6 | [
0,
0,
0,
0,
0,
0
] | intervention 1: EVP-6124 was administered as one 0.1 mg capsule per day for 28 days. intervention 2: EVP-6124 was administered as one 0.3 mg capsule every day for 28 days. intervention 3: EVP-6124 was administered as one 1.0 mg capsule every day for 28 days. intervention 4: Matching placebo was administered as one capsule per day for 28 days. intervention 5: Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study. intervention 6: Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study. | intervention 1: EVP-6124 (0.1 mg/day) intervention 2: EVP-6124 (0.3 mg/day) intervention 3: EVP-6124 (1.0 mg/day) intervention 4: Comparator: Placebo intervention 5: Donepezil intervention 6: Rivastigmine | 4 | San Diego | California | United States | -117.16472 | 32.71571
Hallandale | Florida | United States | -80.14838 | 25.9812
Berlin | New Jersey | United States | -74.92905 | 39.79123
Princeton | New Jersey | United States | -74.65905 | 40.34872 | 49 | 0 | 0 | 0 | NCT00766363 | 1COMPLETED | 2009-03-01 | 2008-10-01 | FORUM Pharmaceuticals Inc | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 386 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | Study to Evaluate the Efficacy and Safety of Aliskiren Hydrochlorothiazide (HCTZ) vs Ramipril in Obese patients (BMI ≥ 30) with Stage 2 Hypertension | null | Hypertension | Hypertension, Obese, aliskiren, hydrochlorothiazide, systolic blood pressure, diastolic blood pressure, ramipril, stage 2 | null | 2 | arm 1: Aliskiren Hydrochlorothiazide(HCTZ) arm 2: Ramipril | [
0,
1
] | 2 | [
0,
0
] | intervention 1: Aliskiren HCTZ 150/12.5 mg: 1 week; Aliskiren HCTZ 300/25 mg: 7 weeks intervention 2: Ramipril 5mg: 1 week; Ramipril 10 mg: 7 weeks | intervention 1: Aliskiren Hydrochlorothiazide intervention 2: Ramipril | 6 | Beverly Hills | California | United States | -118.40036 | 34.07362
Santa Ana | California | United States | -117.86783 | 33.74557
Conyers | Georgia | United States | -84.01769 | 33.66761
Lexington | Kentucky | United States | -84.47772 | 37.98869
Columbia | South Carolina | United States | -81.03481 | 34.00071
Houston | Texas | United States | -95.36327 | 29.76328 | 386 | 0 | 0 | 0 | NCT00772577 | 1COMPLETED | 2009-03-01 | 2008-08-01 | Novartis | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 22 | null | CROSSOVER | 0TREATMENT | 1SINGLE | false | 0ALL | false | Humalog and Humulin-R (recombinant human insulin) are Food and Drug Administration (FDA) approved medications for the treatment of diabetes mellitus. Recombinant human hyaluronidase PH20 (rHuPH20) is approved by the FDA for use as an aid in the absorption and dispersion of other injectable drugs. In this study, rHuPH20 will be co-administered with both Humalog and Humulin-R in order to determine if it improves the absorption of these insulins to more closely mimic the body's natural increase in insulin in response to a meal. | Participants received all 4 interventions in the same order.
Dose-finding visits were conducted to identify the appropriate dose of Humalog and Humulin-R. For each Humalog dose-finding visit, a total of 24 U of rHuPH20 was injected SC per unit of Humalog, corresponding to a mass concentration of 18.2 micrograms per milliliter (μg/mL) rHuPH20 (at final concentration of 91 U/mL of Humalog). For each Humulin-R dose-finding visit, a total of 24 U of rHuPH20 was injected SC per unit of Humulin-R, corresponding to a mass concentration of 20.0 μg/mL rHuPH20 (at final concentration of 100 U/mL of Humulin-R). | Type 1 Diabetes Mellitus | Recombinant Hyaluronidase Type 1 Diabetes Mellitus Humalog Humulin R rHuPH20 Hylenex | null | 1 | arm 1: Humalog + Recombinant human hyaluronidase PH20 (rHuPH20) (Intervention 1): 24 units (U) of rHuPH20 per unit of Humalog, injected subcutaneously (SC), for up to 3 visits until an appropriate dose was identified.
Humalog alone (Intervention 2): a single SC injection of the appropriate identified dose of Humalog, delivered before a liquid meal.
Humulin-R + rHuPH20 (Intervention 3): 24 U of rHuPH20 per unit of Humulin-R, injected SC, for up to 2 visits until an appropriate dose was identified.
Humulin-R alone (Intervention 4): a single SC injection of the appropriate identified dose of Humulin-R, delivered before a liquid meal.
Appropriate dose of either Humalog or Humulin-R was that at which blood glucose following a liquid meal was \<160 milligrams per deciliter (mg/dL) for more than 30 minutes during the first 4 hours after injection and never fell below 60 mg/dL.
All dose finding visits and interventions were separated by 3-10 days. | [
0
] | 4 | [
0,
0,
0,
10
] | intervention 1: None intervention 2: None intervention 3: None intervention 4: None | intervention 1: Humalog intervention 2: Humulin-R intervention 3: Recombinant human hyaluronidase PH20 (rHuPH20) intervention 4: Liquid meal | 1 | Chula Vista | California | United States | -117.0842 | 32.64005 | 87 | 0 | 0 | 0 | NCT00774800 | 1COMPLETED | 2009-03-01 | 2008-10-01 | Halozyme Therapeutics | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
0
] | 10 | RANDOMIZED | CROSSOVER | 7BASIC_SCIENCE | 0NONE | true | 0ALL | false | The purpose of this study is to determine the importance of uptake drug transporters in the drug disposition of warfarin. We predict that the elimination of warfarin will be decreased when co-dosed with an inhibitor of uptake drug transporters. | null | Healthy | warfarin pharmacokinetics drug transporter healthy volunteer drug interaction rifampin | null | 1 | arm 1: None | [
0
] | 2 | [
0,
0
] | intervention 1: warfarin 7.5mg po x 1; rifampin 600mg IV x 1 intervention 2: warfarin 7.5mg po x 1 | intervention 1: warfarin plus rifampin intervention 2: warfarin | 1 | San Francisco | California | United States | -122.41942 | 37.77493 | 10 | 0 | 0 | 0 | NCT00777855 | 1COMPLETED | 2009-03-01 | 2008-11-01 | University of California, San Francisco | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2
] | 27 | RANDOMIZED | PARALLEL | 2DIAGNOSTIC | 2DOUBLE | true | 2MALE | null | This study will compare graded glucose infusion (GGI) to the hyperglycemic clamp (HGC) for assessment of glucose-dependent insulin secretion (GDIS) using exenatide as a probe. | null | The Methodology Assessment of Glucose Dependent Insulin Secretion | null | 3 | arm 1: exenatide 5mcg arm 2: exenatide 1.5mcg arm 3: Placebo | [
1,
1,
2
] | 3 | [
0,
0,
0
] | intervention 1: exenatide in two 5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 5mcg doses will be administered, followed by HCG or GGI. intervention 2: exenatide in two 1.5mcg subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 1.5mcg doses will be administered, followed by HCG or GGI. intervention 3: 5% osmitrol in two 60 mcL subcutaneous doses 120 minutes apart, followed by either HGC or GGI. After a 14 day washout period two additional 60 mcL doses will be administered, followed by HCG or GGI. | intervention 1: Comparator: exenatide intervention 2: Comparator: exenatide intervention 3: Comparator: Placebo | 0 | null | 54 | 0 | 0 | 0 | NCT00782418 | 1COMPLETED | 2009-03-01 | 2008-09-01 | Merck Sharp & Dohme LLC | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
4
] | 82 | RANDOMIZED | CROSSOVER | 0TREATMENT | 3TRIPLE | false | 0ALL | false | The primary efficacy objective of this study is to evaluate the difference in coefficient of fat absorption (CFA) of participants treated with high dose EUR-1008 (APT-1008) versus low dose of EUR-1008 (APT-1008) in the treatment of signs and symptoms of malabsorption in participants with EPI associated with CP. This study is sponsored by Aptalis Pharma (formerly Eurand). | After screening, eligible participants will start the placebo baseline ambulatory phase (4 days). On day 5, they will be hospitalized for three to five days, to undergo a "baseline" 72-hour CFA determination under a controlled diet and using a stool marker to indicate the beginning and end of the controlled diet period, while they continue receiving placebo treatment. At the end of the placebo baseline phase, participants will be randomized to a "high dose followed by a low dose" or to a "low dose followed by a high dose" EUR-1008 (APT-1008) dose sequence and proceed to the first crossover (treatment) phase. Each crossover (treatment) phase will consist of a stabilization period for six days at home, followed by a hospitalization of three to five days to undergo a 72-hour CFA determination using a controlled diet and using a stool marker to indicate the beginning and end of the controlled diet period.
Participants will immediately proceed from the first crossover (treatment) phase to the second without a washout period or return-to-baseline period in between phases. Participants will be stabilized at home for 6 days. Any residual lipase from the prior treatment phase is likely to be a negligible influence on the subsequent CFA determination because participants will be taking the new dose level (high or low) for six days before the beginning of sample collection for a new CFA. This interval is more than enough time for the CFA to be reflective of only the new dose. | Chronic Pancreatitis Exocrine Pancreatic Insufficiency | Chronic Pancreatitis Exocrine Pancreatic Insufficiency | null | 3 | arm 1: None arm 2: None arm 3: None | [
2,
0,
0
] | 3 | [
0,
0,
0
] | intervention 1: Placebo matching to EUR-1008 (APT-1008) capsules orally daily for 4 days home treatment and 3 to 5 days hospital treatment in the baseline run-in phase, which will then be randomized to either high dose or low dose of EUR-1008 (APT-1008). intervention 2: EUR-1008 (APT-1008) total high dose 140,000 lipase USP Lipase units will be given as 7 capsules containing 20,000 USP Lipase units each, orally daily, distributed over the day per gram of fat in diet (possible example: 2 capsules with breakfast, 2 capsules with lunch, 2 capsules with dinner and 1 capsule with a snack) for 6 days home treatment and 3 to 5 days hospital treatment in either first intervention period or second intervention period. intervention 3: EUR-1008 (APT-1008) total low dose 35,000 lipase USP Lipase units will be given as 7 capsules containing 5,000 USP Lipase units each, orally daily, distributed over the day per gram of fat in diet (possible example: 2 capsules with breakfast, 2 capsules with lunch, 2 capsules with dinner and 1 capsule with a snack) for 6 days home treatment and 3 to 5 days hospital treatment in either first intervention period or second intervention period. | intervention 1: Placebo intervention 2: EUR-1008 (APT-1008) High Dose intervention 3: EUR-1008 (APT-1008) Low Dose | 18 | Little Rock | Arkansas | United States | -92.28959 | 34.74648
Los Angeles | California | United States | -118.24368 | 34.05223
Gainesville | Florida | United States | -82.32483 | 29.65163
Port Orange | Florida | United States | -80.99561 | 29.13832
Hines | Illinois | United States | -87.8395 | 41.85364
Iowa Ctiy | Iowa | United States | N/A | N/A
Lexington | Kentucky | United States | -84.47772 | 37.98869
Louisville | Kentucky | United States | -85.75941 | 38.25424
Columbia | Missouri | United States | -92.33407 | 38.95171
Massarenti | Bologna | Italy | N/A | N/A
Rozzano | Milano | Italy | 9.1559 | 45.38193
Largo Agostino Gemelli | Roma | Italy | N/A | N/A
Le Ludovico Scuro | Verona | Italy | N/A | N/A
Simferopol | Autonomous Republic of Crimea | Ukraine | 34.11079 | 44.95719
Donetsk | Donetsk Oblast | Ukraine | 37.80224 | 48.023
Kharkiv | Kharklv | Ukraine | 36.25475 | 49.98177
Kyiv | Kylv | Ukraine | 30.5238 | 50.45466
Kyiv | Kylv | Ukraine | 30.5238 | 50.45466 | 231 | 0 | 0 | 0 | NCT00788593 | 1COMPLETED | 2009-03-01 | 2008-01-01 | Forest Laboratories | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2
] | 24 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | A single rising dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of MK-1006 in Japanese participants with Type 2 Diabetes Mellitus (T2DM). The primary hypothesis of the study is that single doses of MK-1006 will be sufficiently safe and well tolerated, based on the assessment of clinical and laboratory evaluations and adverse experiences, in Japanese participants with T2DM. | null | Diabetes Mellitus, Non-Insulin-Dependent | null | 3 | arm 1: Participants received a single rising dose of MK-1006 (dosed at 15 mg, 30 mg, and 45 mg) or matching placebo to MK-1006 with a 7-day wash-out period between doses. Participants could have received both MK-1006 and matching placebo to MK-1006 over the 3 treatment periods. arm 2: Participants received a single rising dose of MK-1006 (dosed at 60 mg, 80 mg, and 60 mg fed state) or matching placebo to MK-1006 with a 7-day wash-out period between doses. Participants could have received both MK-1006 and matching placebo to MK-1006 over the 3 treatment periods. arm 3: Participants received a single rising dose of MK-1006 (dosed at 100 mg, 140 mg, and 170 mg) or matching placebo to MK-1006 with a 7-day wash-out period between doses. Participants could have received both MK-1006 and matching placebo to MK-1006 over the 3 treatment periods. | [
0,
0,
0
] | 2 | [
0,
0
] | intervention 1: MK-1006 capsules in single oral doses beginning at 15 mg and rising to 45 mg in Panel A, beginning at 60 mg and rising to 80 mg and 60 mg fed state in Panel B, or beginning at 100 mg and rising to 170 mg in Panel C. intervention 2: Matching placebo to MK-1006 in a single oral dose | intervention 1: MK-1006 intervention 2: Placebo | 0 | null | 68 | 0 | 0 | 0 | NCT00791661 | 1COMPLETED | 2009-03-01 | 2008-11-01 | Merck Sharp & Dohme LLC | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
2
] | 49 | RANDOMIZED | CROSSOVER | 7BASIC_SCIENCE | 3TRIPLE | true | 0ALL | false | The FDA has asked Pfizer to assess the risk of linezolid on QT interval (obtained from ECG readings) which could predispose patients to ventricular arrhythmias. This study is conducted to satisfy this requirement. | null | Bacterial Infections | Linezolid, QTc interval, pharmacokinetics, therapeutic dose, supra-therapeutic dose | null | 7 | arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None arm 6: None arm 7: None | [
2,
0,
0,
2,
0,
0,
1
] | 7 | [
0,
0,
0,
0,
0,
0,
0
] | intervention 1: Intravenous, Placebo control for blinding, Normal Saline, Single dose intervention 2: Intravenous, 900 mg linezolid, single dose intervention 3: Intravenous, 1200 mg linezolid, single dose intervention 4: Intravenous, Placebo control for blinding, Normal Saline, Single dose intervention 5: Intravenous, 600 mg linezolid, single dose intervention 6: Intravenous, 1200 mg linezolid, single dose intervention 7: Oral, 400 mg moxifloxacin, single dose | intervention 1: Placebo intervention 2: Linezolid 900 mg intervention 3: Linezolid 1200 mg intervention 4: Placebo intervention 5: Linezolid 600 mg intervention 6: Linezolid 1200 mg intervention 7: Moxifloxacin 400 mg | 1 | Singapore | N/A | Singapore | 103.85007 | 1.28967 | 187 | 0 | 0 | 0 | NCT00795145 | 1COMPLETED | 2009-03-01 | 2008-12-01 | Pfizer | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 27 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | true | 1FEMALE | true | The purpose of this study is to compare treatment outcomes for patients with mixed urinary incontinence (MUI) for whom therapy is initiated with surgery to those for whom therapy is initiated with non-surgical treatment. Women who are bothered by symptoms of both stress and urge incontinence will be randomly assigned to initiate treatment with a surgical (surgery for stress incontinence) vs. a non-surgical (drug and behavioral therapy) approach. Follow-up will be a minimum of 12 Months. | The purpose of this study is to compare treatment outcomes for patients with mixed urinary incontinence (MUI) for whom therapy is initiated with surgery to those for whom therapy is initiated with non-surgical treatment. Women who are bothered by symptoms of both stress and urge incontinence will be randomly assigned to initiate treatment with a surgical (surgery for stress incontinence) vs. a non-surgical (drug and behavioral therapy) approach. Follow-up will be a minimum of 12 Months. | Urinary Incontinence | Stress urinary incontinence, Mixed, Urge | null | 2 | arm 1: Surgical treatment will consist of the following evidence-based stress incontinence procedures: mid-urethral slings (TVT, TOT, TVT-O), fascial slings, and Burch colposuspension. arm 2: The non-surgical treatment will include two components:
1. Pharmacological therapy with any FDA approved overactive bladder (OAB) drug in approved doses; and
2. Behavioral therapy. | [
1,
1
] | 2 | [
0,
3
] | intervention 1: Both oral urge incontinence medication and behavioral treatment intervention 2: Initial surgical (stress incontinence surgery) treatment approach. | intervention 1: Non-Surgical Intervention intervention 2: Surgical | 10 | Birmingham | Alabama | United States | -86.80249 | 33.52066
San Diego | California | United States | -117.16472 | 32.71571
Maywood | Illinois | United States | -87.84312 | 41.8792
Baltimore | Maryland | United States | -76.61219 | 39.29038
Dearborn | Michigan | United States | -83.17631 | 42.32226
Royal Oak | Michigan | United States | -83.14465 | 42.48948
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Dallas | Texas | United States | -96.80667 | 32.78306
San Antonio | Texas | United States | -98.49363 | 29.42412
Salt Lake City | Utah | United States | -111.89105 | 40.76078 | 27 | 0 | 0 | 0 | NCT00803270 | 6TERMINATED | 2009-03-01 | 2008-10-01 | Carelon Research | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
0
] | 51 | RANDOMIZED | PARALLEL | 7BASIC_SCIENCE | 3TRIPLE | true | 0ALL | false | Assess the usefulness of using confocal microscopy to examine changes to the structure of the cornea and to identify any potential consequences of contact lens wear and/or solution use. | Several types of solutions are used in contact lens wear.
Each contact lens solution used to disinfect contacts have different ingredients even though they all disinfect the contacts.
The objective of this study is to examine the layers of the cornea via HRT in order to assess the usefulness of this technology and to identify any potential consequences of contact lens wear and/or care solution used. | Normal Contact Lens Wear | confocal microscopy contact lens wear contact lens solutions sodium fluorescein | null | 3 | arm 1: Subjects that have never worn contacts with no ocular problems were selected. A baseline HRT was performed. Trial contact lenses were soaked in clear care solution for 10 hours. After 10 hours of the lenses soaking in clear care the subject returned. The contacts lenses that were soaked in clear care were inserted onto the patients eyes. The patient then wore the contacts for two hours. After two hours the contact lenses were removed. An HRT was performed immediately after removing the contact lenses. The HRT scans were analyzed for dendritic cell migration, basal cell epithelial density and nerve density and tortuosity. arm 2: Subjects that had worn contacts for at least two weeks without incident were selected. A baseline HRT was performed.Trial contacts lenses were soaked in ReNu contact solution for 10 hours. After 10 hours of the lenses soaking in ReNu the subject returned. The contacts were inserted onto the patients eyes. The patient then wore the contacts for two hours. After two hours the contacts lenses were removed. An HRT both with and without sodium fluorescein was performed immediately after removing the contact lenses.The HRT scans were analyzed for dendritic cell migration, basal cell epithelial density and nerve density and tortuosity. arm 3: Subjects that had worn contacts for at least two weeks without incident were selected. A baseline HRT was performed.Trial contacts lenses were soaked in Optifree Replenish contact solution for 10 hours. After 10 hours of the lenses soaking in Optifree Replenish the subject returned. The contacts were inserted onto the patients eyes. The patient wore contacts the for two hours. After two hours the contacts were removed. An HRT both with and without sodium fluorescein was performed immediately after removing the contact lenses.The HRT scans were analyzed for dendritic cell migration, basal cell epithelial density and nerve density and tortuosity. | [
2,
1,
1
] | 3 | [
0,
0,
0
] | intervention 1: neutralized Clear Care intervention 2: overnight soak in solution intervention 3: overnight soak in solution | intervention 1: Clear Care intervention 2: ReNu intervention 3: OPTI-FREE | 1 | Iowa City | Iowa | United States | -91.53017 | 41.66113 | 51 | 0 | 0 | 0 | NCT00804999 | 1COMPLETED | 2009-03-01 | 2008-11-01 | Christine Sindt | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 7 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | true | RATIONALE: RAD001(Everolimus) may stop the growth of cancer cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the cancer.
PURPOSE: This phase II trial is studying how well RAD001(everolimus) works in treating patients with myelodysplastic syndromes. | OBJECTIVES:
Primary
* Determine the clinical activity (improvement in erythroid response and/or improvement in other cytopenias, bone marrow morphology/cytogenetics) of RAD001(everolimus) in patients with low or intermediate-1 risk myelodysplastic syndromes.
* Assess the toxicity of this drug in these patients.
Secondary
* Examine laboratory correlates (S6K1 levels, angiogenesis pre- and post-treatment) and determine how these correlates correspond to dosing and clinical activity of RAD001(everolimus).
* Evaluate the presence of HLA-DR15 and cytotoxic T-cell populations in patients pre- and post-treatment and correlate this with response to treatment.
* Examine the incidence of the null GSTT-1 phenotype in myelodysplastic syndromes patients and correlate this with response to RAD001(everolimus).
OUTLINE: Patients receive oral RAD001(everolimus) once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or relapse.
Blood samples are collected periodically during study. Samples are analyzed for S6K1 activity, effector T cells by flow cytometry, GSTT-1 by PCR, and HLA-DR15 levels. | Myelodysplastic Syndromes | de novo myelodysplastic syndromes secondary myelodysplastic syndromes previously treated myelodysplastic syndromes | null | 1 | arm 1: RAD001 (everolimus) at 10mg/day with Bone marrow aspirate/biopsy and other laboratory biomarker analysis | [
0
] | 3 | [
0,
10,
3
] | intervention 1: Patients will receive monotherapy with RAD001(everolimus)for 21 days within the 28 day cycle. intervention 2: Laboratory correlates (cytotoxic t cell populations, S6K1 levels, GSTT-1 mutations, and the presence or absence of HLA-DR15) will be assessed to see if any of these correlates correspond to response. intervention 3: Bone marrow aspirate and biopsy with cytogenetics should be obtained within 4 weeks prior to starting drug and at week 33. A bone marrow aspirate and biopsy should also be obtained for patients going off study prior to week 33 (including cytogenetics). The percentage of blasts on the aspirate should be used to determine the IPSS score. | intervention 1: everolimus intervention 2: laboratory biomarker analysis intervention 3: Bone marrow aspirate/biopsy | 1 | Cleveland | Ohio | United States | -81.69541 | 41.4995 | 7 | 0 | 0 | 0 | NCT00809185 | 6TERMINATED | 2009-03-01 | 2005-11-01 | Case Comprehensive Cancer Center | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 106 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | false | This study is conducted to compare and evaluate the effect of administering a high-dose intravenous proton pump inhibitors or high-dose oral Rabeprazole in preventing recurrent bleeding after the endoscopic treatment of bleeding peptic ulcers. | 0.1 % of hospitalized patients are attributed to upper gastrointestinal bleeding every year in the U.S. and Europe, among which peptic ulcer is the most common cause of upper gastrointestinal bleeding. Endoscopic hemostasis procedure in the management of bleeding due to peptic ulcers was safe as well as effective and lowered recurrent bleeding, surgery and mortality. Endoscopic treatment is widely used as an effective and safe method but it has disadvantages including the need for the endoscopy specialist and the likelihood of developing the complications such as perforation or recurrent bleeding although they rarely occur. Thus, less invasive medical treatments with fewer side effects have been continuously studied and among them, gastric acid inhibitors have been studied the most.Acid and pepsin inhibit platelet aggregation, activation of blood coagulation system, and fibrinogen polymerization. Blood clots already formed are digested by pepsin and the activity of pepsin is closely related to intragastric pH level. Therefore, it is known that an elevated intragastric pH facilitates hemostasis process, induces hemostasis by stabilizing hematoma and prevents recurrent bleeding. To suffice these conditions, it is reported that a potent gastric acid inhibitor is needed to maintain intragastric pH of 6 or higher.
For the treatment of bleeding peptic ulcers, the intravenous administration of a high-dose proton pump inhibitor after the initial endoscopic treatment has shown a decline in the frequency of recurrent bleeding as well as surgery. Recent studies reported that the use of oral proton pump inhibitor was effective under certain circumstances in the treatment of bleeding peptic ulcers. However, to date, no study has been conducted to compare the effect of a high-dose intravenous proton pump inhibitor with that of oral Rabeprazole after endoscopic treatment of bleeding peptic ulcers. Therefore, in this study, after administering a high-dose intravenous proton pump inhibitor or high-dose oral Rabeprazole in preventing recurrent bleeding following endoscopic treatment of bleeding peptic ulcers, we are going to compare the rate of recurrent bleeding between the two groups as well as to compare and evaluate the surgery rate, mortality rate and the number of days of hospital stay. | Peptic Ulcer Hemorrhage | peptic ulcer bleeding rabeprazole proton pump inhibitor | null | 2 | arm 1: Oral Rabeprazole 20 mg twice daily for 3 days. From Day 4, oral Rabeprazole 10 mg once daily for 6 weeks as maintenance therapy. arm 2: Intravenous Omeprazole 80 mg as a bolus injection followed by continuous infusion at 8 mg per hour for 3 days. From Day 4, oral Rabeprazole 10 mg once daily for 6 weeks as maintenance therapy. | [
0,
1
] | 2 | [
0,
0
] | intervention 1: Intravenous Omeprazole (brand name: Losec® injection 40 mg) 80 mg as a bolus injection followed by continuous infusion at 8 mg per hour for 3 days. From Day 4, oral Rabeprazole 10 mg once daily for 6 weeks as maintenance therapy. intervention 2: Oral Rabeprazole 20 mg twice daily for 3 days. From Day 4, oral Rabeprazole 10 mg once daily for 6 weeks as maintenance therapy. | intervention 1: omeprazole sodium IV intervention 2: Rabeprazole | 2 | Bucheon-si | Kyungkido | South Korea | 126.78306 | 37.49889
Uijeongbu-si | Kyungkido | South Korea | 127.0474 | 37.7415 | 106 | 0 | 0 | 0 | NCT00838682 | 6TERMINATED | 2009-03-01 | 2006-04-01 | The Catholic University of Korea | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2
] | 24 | RANDOMIZED | CROSSOVER | 0TREATMENT | 0NONE | true | 0ALL | false | The objective of the study is to compare the pharmacokinetic profiles of extended-release and immediate-release trazodone formulations | The bioavailability of once-daily trazodone extended-release 300 mg caplets (test product) and trazodone immediate-release 100 mg tablets administered q8h (reference product) will be compared in healthy adult volunteers in a randomized, crossover fashion. Morning doses will be administered after an overnight fast. Blood samples will be collected predose and at pre-defined times over 72 hours following the morning dose. Pharmacokinetic parameters will be analyzed using ANOVA. Comparative bioavailability will be assessed on the basis of the ratio of least-squares means and/or 90% confidence interval criteria. | Healthy | bioavailability pharmacokinetics healthy crossover trazodone | null | 2 | arm 1: None arm 2: None | [
0,
1
] | 2 | [
0,
0
] | intervention 1: 100 mg immediate-release tablet, dosing q8h intervention 2: 300 mg extended-release caplet, single dose | intervention 1: Trazodone HCl intervention 2: Trazodone HCl | 1 | Laval | Quebec | Canada | -73.692 | 45.56995 | 45 | 0 | 0 | 0 | NCT00839072 | 1COMPLETED | 2009-03-01 | 2009-02-01 | Labopharm Inc. | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2
] | 15 | RANDOMIZED | PARALLEL | 0TREATMENT | 3TRIPLE | false | 0ALL | false | The purpose of the study is to evaluate the effect of LX3305 on methotrexate (MTX) pharmacokinetics and to evaluate the safety and tolerability of LX3305 given over 14 days in subjects with stable rheumatoid arthritis that are receiving stable doses of MTX. | null | Rheumatoid Arthritis | null | 2 | arm 1: Daily oral intake of LX3305 for 14 days. arm 2: Matching placebo dosing with daily oral intake for 14 days. | [
0,
2
] | 3 | [
0,
0,
0
] | intervention 1: Daily oral intake of LX3305 for 14 days. intervention 2: Matching placebo dosing with daily oral intake for 14 days. intervention 3: Once weekly stable-dose methotrexate. | intervention 1: LX3305 intervention 2: LX3305 Placebo intervention 3: Methotrexate | 1 | Dallas | Texas | United States | -96.80667 | 32.78306 | 15 | 0 | 0 | 0 | NCT00847886 | 1COMPLETED | 2009-03-01 | 2009-02-01 | Lexicon Pharmaceuticals | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
3
] | 56 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | true | This study serves to compare the effectiveness of treating cutaneous leishmaniasis with either intravenous sodium stibogluconate or direct heat therapy using the ThermoMed-TM device. | A total of 56 Department of Defense health care beneficiaries, 18 years of age or older and diagnosed with cutaneous leishmaniasis, were planned to be treated with either intravenous sodium stibogluconate (Pentostam-TM) or the ThermoMed-TM device of Thermosurgery Technologies, Inc. at the Walter Reed Army Medical Center. Pentostam is the standard of care for this disease, but the i.v. administration and the many known side effects prompt the search for an improved method of treating this disease, especially for milder cases. This study compares the safety and efficacy of these two treatment approached. | Cutaneous Leishmaniasis | null | 2 | arm 1: 20 mg/kg/day Sodium stibogluconate intravenous arm 2: ThermoMed device, single heat treatment at 50 degrees Celsius | [
1,
0
] | 2 | [
0,
1
] | intervention 1: intravenous 20 mg/kg/day for 10 days intervention 2: ThermoMed heat treatment device, one treatment | intervention 1: Sodium stibogluconate (Pentostam) intervention 2: ThermoMed | 1 | Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511 | 56 | 0 | 0 | 0 | NCT00884377 | 1COMPLETED | 2009-03-01 | 2004-02-01 | U.S. Army Medical Research and Development Command | 1FED | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
2
] | 24 | NON_RANDOMIZED | SINGLE_GROUP | 7BASIC_SCIENCE | 0NONE | true | 0ALL | false | Colchicine is a substrate for cytochrome P450 3A4 (CYP3A4). In-vitro studies have indicated that the ortho-and para-hydroxylated metabolites of atorvastatin may be CYP3A4/5 competitive and mechanism-based inhibitors (MBI). This study will evaluate the effect of multiple doses of atorvastatin on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. A secondary objective is to evaluate the safety and tolerability of this regimen in healthy volunteers. All study subjects will be monitored for adverse events throughout the study period. | Colchicine is a substrate for cytochrome P450 3A4 (CYP3A4). In-vitro studies have indicated that the ortho-and para-hydroxylated metabolites of atorvastatin may be CYP3A4 /5 competitive and mechanism-based inhibitors (MBI). This study will evaluate the effect of multiple doses of atorvastatin on the pharmacokinetic profile of a single 0.6 mg dose of colchicine. Twenty-four healthy, non-smoking, non-obese, non-pregnant adult volunteers between the ages of 18 and 45 will be given one oral dose of colchicine (1 x 0.6 mg tablet) on Day 1 after an overnight fast. Blood samples will be drawn from all participants before dosing and for 24 hours post-dose at times sufficient to adequately define the pharmacokinetics of colchicine. After a 14 day washout period, starting on the morning of Day 15 and continuing through Day 27, subjects will return to the clinic for once daily administration of atorvastatin (1 x 40 mg tablet) after an overnight fast. After taking the first dose of atorvastatin on Day 15, subjects will remain in the clinic for 1 hour post-dose administration for observation. On the morning of Day 28 after an overnight fast, all study participants will receive a co-administered single oral dose of colchicine (1 x 0.6 mg tablet) and atorvastatin (1 x 40 mg tablet). Blood samples will be drawn from all participants before dosing and for twenty-four hours post-dose at times sufficient to adequately define the pharmacokinetics of colchicine in the presence of atorvastatin at steady state. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Seated blood pressure and pulse, respiratory rate and temperature will be measured at screening, baseline and upon study discharge. Blood pressure and pulse will also be measured pre-dose and at 1 and 2 hours post-dose on Days 1 and 28 to coincide with peak plasma concentrations of colchicine and atorvastatin. All adverse events whether elicited by query, spontaneously reported, or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form. | Healthy | pharmacokinetics | null | 2 | arm 1: baseline colchicine pharmacokinetics arm 2: Colchicine pharmacokinetics in the presence of atorvastatin at steady state. | [
1,
0
] | 3 | [
0,
0,
0
] | intervention 1: A single dose of 0.6 mg colchicine administered alone in the morning on Day 1. intervention 2: Atorvastatin (1 x 40 mg tablet) administered once daily on Days 15-28. intervention 3: A single dose of 0.6 mg colchicine administered with a single dose of 40 mg atorvastatin in the morning on Day 28 after an overnight fast. | intervention 1: Colchicine intervention 2: Atorvastatin intervention 3: Colchicine | 1 | Fargo | North Dakota | United States | -96.7898 | 46.87719 | 71 | 0 | 0 | 0 | NCT00960323 | 1COMPLETED | 2009-03-01 | 2009-02-01 | Mutual Pharmaceutical Company, Inc. | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2
] | 18 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | An open-label, 3-period, fixed-sequence study in a panel of 18 HIV-infected patients on MK0518 as part of a stable treatment regimen for HIV. | null | HIV-1 Infection HIV Infections | Treatment experienced | null | 3 | arm 1: MK0518 arm 2: famotidine + MK0518 arm 3: omeprazole + MK0518 | [
0,
0,
0
] | 3 | [
0,
0,
0
] | intervention 1: 400 mg oral tablet of MK0518 once every 12 hours. Period 1 duration is one day, Period 2 duration is one day, Period 3 duration is five days. intervention 2: Single 20 mg famotidine oral tablet taken 2 hours prior to administration of AM dose of MK0518 intervention 3: 20 mg oral tablet of omeprazole, once daily for 5 days | intervention 1: MK0518 (Raltegravir) intervention 2: famotidine intervention 3: omeprazole | 0 | null | 72 | 0 | 0 | 0 | NCT01000818 | 1COMPLETED | 2009-03-01 | 2008-06-01 | Merck Sharp & Dohme LLC | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 65 | RANDOMIZED | CROSSOVER | 0TREATMENT | 1SINGLE | true | 0ALL | false | This study is to evaluate the effect of fluoride dentrifrices on enamel with artificial caries lesions in an in situ model | null | Caries | remineralization enamel in situ fluoride caries | null | 6 | arm 1: Placebo arm 2: Sodium fluoride toothpaste arm 3: Amine Fluoride arm 4: Dose response arm 5: Sodium monofluorophosphate/sodium fluoride Toothpaste arm 6: None | [
5,
0,
1,
5,
1,
2
] | 5 | [
0,
0,
0,
0,
0
] | intervention 1: Test product intervention 2: Test product intervention 3: test product intervention 4: placebo and washout treatment intervention 5: dose response | intervention 1: Sodium Fluoride Toothpaste intervention 2: Amine Fluoride Toothpaste intervention 3: Sodium monofluorophosphate/Sodium Fluoride Toothpaste intervention 4: Placebo intervention 5: 675 ppmf toothpaste | 0 | null | 356 | 0 | 0 | 0 | NCT01005966 | 1COMPLETED | 2009-03-01 | 2008-11-01 | GlaxoSmithKline | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 27 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | true | The objective of the study is to determine if treatment with Ramelteon will help to improve insomnia in older adults with co-existent insomnia and sleep apnea. The primary study objective is sleep latency (a measure of insomnia). The hypothesis is that sleep latency will be reduced in subjects taking Ramelteon relative to the placebo arm. The secondary study objective is to determine if subject compliance with CPAP treatment of their sleep apnea is improved in subjects taking Ramelteon (their compliance may be improved because they would have less insomnia due to Ramelteon treatment when using their CPAP). The hypothesis is that compliance with CPAP will be improved in subjects taking Ramelteon relative to the placebo arm. | Randomized, double-blind, placebo-controlled, parallel arm clinical trial with two study arms. | Insomnia Obstructive Sleep Apnea | null | 2 | arm 1: Ramelteon 8 mg oral before bedtime arm 2: None | [
0,
2
] | 2 | [
0,
0
] | intervention 1: Ramelteon (rozerem) 8mg oral before bedtime intervention 2: placebo | intervention 1: rozerem intervention 2: Placebo | 1 | Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238 | 21 | 0 | 0 | 0 | NCT01048242 | 1COMPLETED | 2009-03-01 | 2006-07-01 | University of Pennsylvania | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
4
] | 30 | RANDOMIZED | CROSSOVER | null | 0NONE | true | 0ALL | false | This randomized, crossover study is to evaluate the early effectiveness, defined as effect on intragastric pH during the first 4 hours after dosing, of Zegerid, Prilosec over-the-counter (OTC) Tablets, and placebo on the 4th day of treatment to inhibit acid secretion. Additional purposes are to:
1. provide pharmacodynamic evidence comparing 24-hr inhibition of acid secretion on the 1st, 4th, and 11th days of dosing with each of the indicated treatments;
2. compare Zegerid and Prilosec OTC for achieving their steady-state effects for controlling 24-hr gastric acidity at steady-state on the 4th and 11th day of dosing.
3. evaluate early effectiveness, defined as effect on intragastric pH during the first 4 hours after administration, of Zegerid, Prilosec OTC Tablets, and placebo on acid inhibition at steady-state when administered on the 11th day of dosing. | Participants were randomized in a 3-way crossover design and received, in random order, Zegerid OTC Capsules (20 mg omeprazole and 1100 mg sodium bicarbonate), Prilosec OTC Tablets (20 mg-equivalent omeprazole), and Placebo Capsules. Participants received each treatment for 11 days. There was a minimum of a 2-week washout period between treatment arms. | Intragastric Acidity | Gastric Acid Human Experimentation | null | 3 | arm 1: 20 mg omeprazole and 1100 mg sodium bicarbonate arm 2: 20.6 mg omeprazole-magnesium complex. arm 3: Inert substance | [
0,
1,
2
] | 3 | [
0,
0,
10
] | intervention 1: Zegerid taken once daily for 11 days. intervention 2: Prilosec OTC™ Tablets taken once daily for 11 days. intervention 3: Placebo taken once daily for 11 days. | intervention 1: Zegerid intervention 2: Prilosec OTC™ Tablets intervention 3: Placebo | 0 | null | 88 | 0 | 0 | 0 | NCT01077076 | 1COMPLETED | 2009-03-01 | 2008-12-01 | Bayer | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 237 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | Primary objective:
To demonstrate the long-term efficacy (response to treatment during initial therapy, time to relapse without treatment, durability and lesional recurrence during maintenance therapy) of V0034 CR 01B cream on uraemic xerosis in the real-life setting.
Secondary objectives:
1. To assess the local tolerance of V0034 CR 01B after long-term use
2. To assess the patient benefit and acceptability of V0034 CR 01B | null | Uremic Xerosis | null | 2 | arm 1: cream arm 2: cream | [
0,
2
] | 2 | [
0,
0
] | intervention 1: None intervention 2: None | intervention 1: V0034CR01B intervention 2: V0034CR01B vehicle | 0 | null | 235 | 0 | 0 | 0 | NCT01084148 | 1COMPLETED | 2009-03-01 | 2007-01-01 | Orfagen | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
0
] | 200 | RANDOMIZED | PARALLEL | 1PREVENTION | 3TRIPLE | false | 0ALL | true | To determine whether intraoperative tight glycaemic control can reduce postoperative infection, morbidity and mortality | Hyperglycaemia develops frequently in patients undergoing cardiac surgery, especially following cardiopulmonary bypass (CPB). Recent evidence suggests that acute hyperglycaemia adversely affects immune function, wound healing and cardiovascular function. | Nosocomial Infection External Causes of Morbidity and Mortality Hypoglycemia | tight glycemic control cardiac surgery | null | 2 | arm 1: TGC used hyperinsulinaemic normoglycaemic clamp with modified glucose-insulin-potassium to control blood sugar. The insulin (HumulinTM R, Lilly pharma, Germany) was diluted with normal saline to the concentration 1 IU. mL-1 and was infused continuously throughout the operations at a fixed rate of 0.3 IU. kg-1.h-1 but the maximal rate was 20 IU/ h. A separate mixture of glucose 25% (A.N.B Laboratories, Thailand) 50 mL, potassium chloride (Nida pharma, Thailand) 20 mEq and magnesium sulfate (Atlantic, Thailand) 2 gm was infused at 0.75 mL.kg-1.h-1 and was adjusted to maintain blood glucose levels 80-150 mg/dL. arm 2: Conventional glycaemic control aims to control blood sugar less than 250 mg%. Insulin was given bolusly if the blood sugar more than 250 mg%. | [
0,
2
] | 2 | [
0,
0
] | intervention 1: TGC used hyperinsulinaemic normoglycaemic clamp with modified glucose-insulin-potassium to control blood sugar. The insulin (HumulinTM R, Lilly pharma, Germany) was diluted with normal saline to the concentration 1 IU. mL-1 and was infused continuously throughout the operations at a fixed rate of 0.3 IU. kg-1.h-1 but the maximal rate was 20 IU/ h. A separate mixture of glucose 25% (A.N.B Laboratories, Thailand) 50 mL, potassium chloride (Nida pharma, Thailand) 20 mEq and magnesium sulfate (Atlantic, Thailand) 2 gm was infused at 0.75 mL.kg-1.h-1 and was adjusted to maintain blood glucose levels 80-150 mg/dL. intervention 2: Conventional glycaemic control aims to control blood sugar less than 250 mg%. Insulin was given bolusly if the blood sugar more than 250 mg%. | intervention 1: TGC intervention 2: Conventional glycaemic control | 1 | Hat Yai | Changwat Songkhla | Thailand | 100.47668 | 7.00836 | 199 | 0 | 0 | 0 | NCT01225159 | 6TERMINATED | 2009-03-01 | 2008-09-01 | Prince of Songkla University | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 56 | RANDOMIZED | PARALLEL | 7BASIC_SCIENCE | 0NONE | false | 0ALL | true | The primary goal of the study is to measure in the intact human heart, the alterations in gene expression over time that are associated with reverse remodeling in response to β-blockade. The second goal is to investigate the signaling mechanisms which in turn are responsible for these changes in gene expression, and the third goal is to determine the relationship between intrinsic systolic dysfunction and remodeling of the left ventricle. This will be accomplished by measuring ventricular size, function, and gene expression in myocardial tissue samples obtained by percutaneous biopsy prior to initiation of β-blockade and at 3 and 12 months after start of therapy. The specific Aims and Hypotheses to be tested are:
1. Aim: Determine the changes in gene expression associated with changes in intrinsic systolic function and with functional decompensation in the intact, failing human heart.
a. Hypothesis: Changes in the expression of select genes precede or accompany changes in left ventricular systolic function in humans with idiopathic dilated cardiomyopathy (IDC).
2. Aim: Identify signaling mechanisms responsible for alterations in expression of key genes involved in mediation of ventricular hypertrophy or contractile dysfunction.
a. Hypothesis: Myocardial-failure-associated regulation of select messenger ribonucleic acids and proteins are related to left ventricular wall stress and neurohormonal signaling.
3. Aim: In the relationship between contractile dysfunction and dilatation/remodeling, determine the relationship between contractile dysfunction and structural remodeling.
b. Hypothesis: the contractile dysfunction is primary and structural remodeling secondary. | null | Idiopathic Dilated Cardiomyopathy | ejection fraction beta-blocker carvedilol metoprolol myocardial gene expression human heart ventricular remodeling wall stress adrenergic signaling myosin heavy chain | null | 4 | arm 1: Patients with normal ejection fraction who underwent a single myocardial biopsy and received no β-blocker therapy arm 2: Idiopathic dilated cardiomyopathy patients randomized to metoprolol succinate titrated to a goal of 200 mg by mouth daily for 18 months arm 3: Idiopathic dilated cardiomyopathy patients who were randomized to receive metoprolol succinate and doxazosin titrated to a goal of 200 mg and 8 mg by mouth daily for 18 months arm 4: Idiopathic dilated cardiomyopathy patients who were randomized to receive carvedilol titrated to a goal of 25 mg by mouth twice daily for 18 months | [
4,
1,
1,
1
] | 3 | [
0,
0,
0
] | intervention 1: None intervention 2: None intervention 3: None | intervention 1: Carvedilol intervention 2: Metoprolol succinate intervention 3: Metoprolol succinate + doxazosin | 2 | Denver | Colorado | United States | -104.9847 | 39.73915
Salt Lake City | Utah | United States | -111.89105 | 40.76078 | 47 | 0 | 0 | 0 | NCT01798992 | 1COMPLETED | 2009-03-01 | 2000-09-01 | University of Colorado, Denver | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 121 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 1FEMALE | null | The purpose of this research study is to compare induction of labor using a foley catheter bulb with a low dose of oxytocin versus a foley catheter bulb with an increasing dose of oxytocin. A foley catheter bulb with or without oxytocin is a common method of labor induction in patients whose cervix is not significantly dilated or thinned out (effaced). Oxytocin (pitocin) is a medicine used to increase the number and strength of the womb's contractions. | null | Induction of Labor | induction of labor pitocin foley bulb | null | 2 | arm 1: Subjects in this arm will receive a standard infusion protocol of pitocin starting at 1 milliunit/minute (mius/min) and increasing 2 milliunits per minute every 30 minutes. arm 2: Subjects in this arm will receive a fixed low dose pitocin infusion protocol of 2 mius/min. | [
1,
1
] | 1 | [
0
] | intervention 1: None | intervention 1: pitocin | 0 | null | 116 | 0 | 0 | 0 | NCT02150954 | 1COMPLETED | 2009-03-01 | 2007-12-01 | Duke University | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
0
] | 20 | RANDOMIZED | PARALLEL | 5SCREENING | 0NONE | false | 0ALL | false | The aim of the study is to evaluate the efficacy of new immunosuppressive protocol based on two applications of anti-CD52 MabCampath (Alemtuzumab) a single dose of anti-TNF-α Remicade (infliximab) monoclonal antibodies in the early posttransplant period followed by either monotherapy based on tacrolimus or sirolimus. | null | Kidney Transplantation | null | 2 | arm 1: Patients received two applications of anti-CD52 MabCampath (Alemtuzumab), a single dose of anti-TNF-α Remicade (Infliximab) monoclonal antibodies in the early posttransplant period. First 14 days patients received tacrolimus monotherapy, at post-operative day (POD) 14, they were randomized to sirolimus monotherapy. arm 2: Patients received two applications of anti-CD52 MabCampath (Alemtuzumab), a single dose of anti-TNF-α Remicade (Infliximab) monoclonal antibodies in the early posttransplant period. First 14 days patients received tacrolimus monotherapy, at POD 14, they were randomized to tacrolimus monotherapy. | [
1,
1
] | 4 | [
0,
0,
0,
0
] | intervention 1: Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively. intervention 2: Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively. intervention 3: Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively. intervention 4: Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively. | intervention 1: MabCampath, intervention 2: Remicade intervention 3: Sirolimus intervention 4: Tacrolimus | 0 | null | 20 | 0 | 0 | 0 | NCT02711202 | 1COMPLETED | 2009-03-01 | 2007-01-01 | Institute for Clinical and Experimental Medicine | 2OTHER_GOV | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
0
] | 149 | RANDOMIZED | PARALLEL | 9OTHER | 0NONE | false | 0ALL | false | Delayed prescriptions have been shown to lower antibiotic use for upper respiratory tract infections (which are mostly viral).
This trial will test the hypothesis that if the clinician post-dates the delayed prescription by 2 days, rather than dating it on the day the patient is seen, there will be a further drop in the rate of antibiotic use. | 6 family doctors and 2 nurse practitioners in a small rural town will issue delayed antibiotic prescriptions to adult patients with new acute respiratory tract infections. The delayed prescriptions will be randomly dated for either the day of the office visit, or 2 days later. The 2 local pharmacies will note whether the prescription is cashed, and when.
It is hypothesised that post-dating the prescription will result in a reduced cashing rate.
Each arm of the study (Usual v Post-Dated) will contain 75 subjects. This sample will have the power to detect a 25% change in prescription use. | Acute Upper Respiratory Tract Infections | Respiratory infections Primary care Antibiotics Delayed prescriptions | null | 2 | arm 1: a delayed prescription dated 2 days after clinical office visit arm 2: usual date | [
5,
5
] | 2 | [
10,
0
] | intervention 1: None intervention 2: None | intervention 1: A delayed prescription dated 2 days after clinical office visit intervention 2: Usual Dated | 1 | St. John's | Newfoundland and Labrador | Canada | -52.70931 | 47.56494 | 0 | 0 | 0 | 0 | NCT02732847 | 1COMPLETED | 2009-03-01 | 2007-10-01 | Memorial University of Newfoundland | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 27 | RANDOMIZED | CROSSOVER | 0TREATMENT | 2DOUBLE | false | 0ALL | false | This study is being conducted to evaluate sitaxsentan dosing in subjects with chronic kidney disease. | null | Chronic Kidney Disease | Chronic Kidney Disease Sitaxsentan | null | 3 | arm 1: Sitaxsentan sodium 100 mg orally administered once daily (double blind arm) arm 2: Nifedipine 30 mg extended release tablets, orally administered once daily (open label arm) arm 3: Placebo for sitaxsentan, orally administered once daily (double blind arm) | [
0,
1,
2
] | 3 | [
0,
0,
0
] | intervention 1: Sitaxsentan sodium 100 mg orally administered once daily (double blind arm) intervention 2: Nifedipine = 30 mg extended release tablets, orally administered once daily (open label arm) intervention 3: Placebo for sitaxsentan, orally administered once daily (double blind arm) | intervention 1: Open intervention 2: Nifedipine intervention 3: Placebo | 2 | Edinburgh | Scotland | United Kingdom | -3.19648 | 55.95206
Edinburgh | Scotland | United Kingdom | -3.19648 | 55.95206 | 81 | 0 | 0 | 0 | NCT00810732 | 1COMPLETED | 2009-03-06 | 2007-05-09 | Pfizer | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 67 | RANDOMIZED | CROSSOVER | 0TREATMENT | 2DOUBLE | false | 0ALL | false | This is a Phase 2 multicenter, randomized, double-blind trial of MK-8777 (Org 26576, SCH 900777) in adult subjects with Attention-Deficit/Hyperactivity Disorder (ADHD). MK-8777 or placebo will be administered in a crossover fashion for two 3-week treatment periods. The two 3-week treatment periods will be separated by a 2-week placebo washout period.
The primary objective is to compare the efficacy of various doses of MK-8777 to that of placebo in the treatment of ADHD symptoms in adults. | null | Attention Deficit Hyperactivity Disorder | randomized double blind placebo controlled | null | 4 | arm 1: Participants receive a fixed dose (FD) of MK-8777 100 mg twice each day (BID) for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive a fixed dose of placebo (PBO) BID for 3 weeks (Treatment Period 2). arm 2: Participants receive a fixed dose of placebo BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive a fixed dose of MK-8777 100 mg BID for 3 weeks (Treatment Period 2). arm 3: Participants receive rising doses (RD) of MK-8777 100-300 mg BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive rising doses of placebo BID for 3 weeks (Treatment Period 2). arm 4: Participants receive rising doses of placebo BID for 3 weeks (Treatment Period 1). After a 2-week placebo washout period, participants receive rising doses of MK-8777 100-300 mg BID for 3 weeks (Treatment Period 2). | [
0,
0,
0,
2
] | 2 | [
0,
0
] | intervention 1: None intervention 2: None | intervention 1: MK-8777 intervention 2: Placebo | 0 | null | 117 | 0 | 0 | 0 | NCT00610441 | 1COMPLETED | 2009-03-09 | 2008-04-01 | Merck Sharp & Dohme LLC | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 62 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | This study was designed to evaluate the pharmacokinetic profile, safety and efficacy in Parkinson's Disease patients. | null | Parkinson Disease | Parkinson's Disease PD | null | 1 | arm 1: None | [
0
] | 1 | [
0
] | intervention 1: Subjects will take the investigational drug once daily at the same time each day, it is recommended that this is in the morning for optimal benefit. Investigational drug is taken for 52 weeks, starting on the next day of the Week 0 visit. One tablet of ropinirole PR/XR 2 mg tablets will be orally dosed as the initial dose. The dose will be titrated weekly by 2 mg/day, and increased to 8 mg/day in Week 4. From Week 5 up to 16, the dose will be increased at minimum intervals of one week between titration steps until sufficient efficacy is obtained, according to individual clinical response and tolerability (the dose may be titrated up to 16 mg/day). In Week 16 and further, treatment dose at Week 16 will be continuously administered up to Week 52. If insufficient efficacy is judged in a subject during treatment, or unable to maintain the dose due to adverse event, the treatment dose may be changed. The dose is down tapered according to the maintenance dose at Week 52 (or withdrawal). | intervention 1: Ropinirole prolonged release/extended release(PR/XR) | 12 | Aichi | N/A | Japan | 130.62158 | 32.51879
Aichi | N/A | Japan | 130.62158 | 32.51879
Chiba | N/A | Japan | 140.11667 | 35.6
Ehime | N/A | Japan | N/A | N/A
Hokkaido | N/A | Japan | N/A | N/A
Kanagawa | N/A | Japan | 139.91667 | 37.58333
Kyoto | N/A | Japan | 135.75385 | 35.02107
Numakunai | N/A | Japan | 141.21667 | 39.96667
Osaka | N/A | Japan | 135.50107 | 34.69379
Saitama | N/A | Japan | 139.65657 | 35.90807
Tokyo | N/A | Japan | 139.69171 | 35.6895
Tokyo | N/A | Japan | 139.69171 | 35.6895 | 124 | 0 | 0 | 0 | NCT00434304 | 1COMPLETED | 2009-03-10 | 2007-04-09 | GlaxoSmithKline | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2,
3
] | 51 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | true | Objectives:
The primary objective of the study was to determine the ability of ITF2357, administered orally at the dose of 50 mg b.i.d. for 8 consecutive weeks, to induce complete healing of mucosal ulcerations of ileum and/or colon, assessed by endoscopy, in patients with endoscopic and clinical evidence of active moderate-to-severe Crohn's disease not controlled by conventional therapies.
The secondary objectives of the study were:
* to evaluate the effect of ITF2357 on endoscopic disease activity assessed using both the Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score of Crohn's Disease (SES-CD);
* to evaluate the effect of ITF2357 on clinical disease activity, assessed using the Crohn's Disease Activity Index (CDAI);
* to assess the safety and tolerability of ITF2357; to assess the pharmacokinetic profile of ITF2357. | The study was conducted according to a randomized, double-blind placebo-controlled, parallel group design in up to 25 clinical sites in Europe.
Eligible patients were randomly assigned to two parallel treatment groups (1:1 randomization ratio) receiving either ITF2357, as hard gelatine capsule for oral administration, at the dose of 50 mg b.i.d. (total daily dose of 100 mg), or matching placebo capsules.
Treatment was administered on an outpatient basis for 8 consecutive weeks, followed by a 4-week follow-up.
During screening, in the 8-week treatment period and in the 4-week follow-up period, patients attended scheduled visits, with physical and laboratory assessments, in order to monitor disease evolution and safety and tolerability of ITF2357.
The study was planned to be conducted in up to 80 patients of both genders, with established diagnosis of CD, who presented with ulcerations greater than aphthous ulcers in at least one of the five bowel segments investigated endoscopically, from the ileum to the rectum, with endoscopic and clinical evidence of moderate-to-severe active disease, not controlled by on-going treatment with conventional therapies such as 5-aminosalicylates, steroids or immunosuppressants.
The present study has been designed in order to assessed wether short-term (8 weeks) treatment with oral ITF2357 can induce disease improvement in a substantial proportion of patients.
Its aim to evaluate whether a short term treatment with ITF2357 for 8 weeks, at the selected dose of 50 mg b.i.d., is able to induce healing of mucosal lesions, evaluated endoscopically, in patients with endoscopic and clinical evidence of moderate-to-severe active Crohn's disease, not controlled by ongoing treatment with conventional therapies such as 5-aminosalicylates, steroids or immunosuppressants, was not addressed and the study was prematurely interrupted according to IDSMC (Independent Data and Safety Monitoring Committee) decision, based on the results of the interim analysis, which did not demonstrate any benefit of ITF2357 over placebo in the primary variable rate of patients achieving complete healing at week 8.
There was also no evidence of benefits in patients treated with ITF2357 compared to placebo in the secondary efficacy endpoints (full remission rate, remission rate, CDEIS endoscopic response, changes from baseline of CDEIS score and SES-CD score, changes from baseline of CDAI score, CDAI remission rate, and CDAI response rate). | Crohn's Disease | null | 2 | arm 1: Oral matching placebo capsules, administered bid. arm 2: Oral ITF2357 50 mg bid | [
2,
0
] | 2 | [
0,
10
] | intervention 1: ITF2357 was administered as hard gelatin capsules for oral administration at the dose strength of 50 mg. Capsules were administered as follow: one capsule in the morning and one in the evening. intervention 2: Placebo was supplied as matching capsules for oral administration with the same outer appearance of the study drug and with the same dosing scheme (one capsule in the morning and one in the evening) | intervention 1: ITF2357 intervention 2: Placebo | 10 | Assebroek | N/A | Belgium | 3.2623 | 51.19367
Bonheiden | N/A | Belgium | 4.54714 | 51.02261
Brussels | N/A | Belgium | 4.34878 | 50.85045
Ghent | N/A | Belgium | 3.71667 | 51.05
Kortrijk | N/A | Belgium | 3.26487 | 50.82803
Leuven | N/A | Belgium | 4.70093 | 50.87959
Rozzano | N/A | Italy | 9.1559 | 45.38193
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Leiden | N/A | Netherlands | 4.49306 | 52.15833 | 51 | 0 | 0 | 0 | NCT00792740 | 6TERMINATED | 2009-03-11 | 2007-10-22 | Italfarmaco | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
4
] | 120 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | This study will evaluate the safety and effectiveness of MabThera (rituximab) in patients with active rheumatoid arthritis who are receiving methotrexate, and who have a previous or current inadequate response to one prior anti-TNF therapy. All patients will receive MabThera 1000 mg as an intravenous infusion on days 1 and 15. After the initial study phase of 24 weeks, eligible patients may receive one re-treatment with MabThera. The anticipated time on study treatment is 48 weeks. | null | Rheumatoid Arthritis | null | 1 | arm 1: None | [
0
] | 1 | [
0
] | intervention 1: 1000 mg intravenously on Days 1 and 15 | intervention 1: rituximab | 41 | Edmonton | Alberta | Canada | -113.46871 | 53.55014
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Kelowna | British Columbia | Canada | -119.48568 | 49.88307
Vancouver | British Columbia | Canada | -123.11934 | 49.24966
Victoria | British Columbia | Canada | -123.35155 | 48.4359
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
St. John's | Newfoundland and Labrador | Canada | -52.70931 | 47.56494
St. John's | Newfoundland and Labrador | Canada | -52.70931 | 47.56494
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Nepean | Ontario | Canada | -75.7225 | 45.33619
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Thunder Bay | Ontario | Canada | -89.25018 | 48.38202
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Windsor | Ontario | Canada | -83.01654 | 42.30008
Laval | Quebec | Canada | -73.692 | 45.56995
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Québec | Quebec | Canada | -71.21454 | 46.81228
Saint-Eustache | Quebec | Canada | -73.90554 | 45.565
Sainte-Foy | Quebec | Canada | -71.29217 | 46.78139
Sherbrooke | Quebec | Canada | -71.89908 | 45.40008
Trois-Rivières | Quebec | Canada | -72.5477 | 46.34515
Borås | N/A | Sweden | 12.9401 | 57.72101
Falun | N/A | Sweden | 15.62597 | 60.60357
Gothenburg | N/A | Sweden | 11.96679 | 57.70716
Jönköping | N/A | Sweden | 14.15618 | 57.78145
Kalmar | N/A | Sweden | 16.36163 | 56.66157
Karlskrona | N/A | Sweden | 15.58661 | 56.16156
Luleå | N/A | Sweden | 22.15465 | 65.58415
Malmo | N/A | Sweden | 13.00073 | 55.60587
Oskarström | N/A | Sweden | 12.96667 | 56.8
Skövde | N/A | Sweden | 13.84506 | 58.39118
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Sundsvall | N/A | Sweden | 17.3063 | 62.39129 | 197 | 0 | 0 | 0 | NCT01272908 | 1COMPLETED | 2009-03-12 | 2006-07-18 | Hoffmann-La Roche | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
2
] | 64 | RANDOMIZED | CROSSOVER | 0TREATMENT | 2DOUBLE | false | 0ALL | false | This study will assess the safety of telcagepant in coronary artery disease (CAD) participants with stable angina during exercise treadmill testing and evaluate whether calcitonin gene-related peptide (CGRP) receptor antagonism by telcagepant reduces exercise tolerance in these participants. Primary hypothesis is that telcagepant does not significantly decrease exercise duration compared to placebo, as measured by a treadmill exercise test; that is, the true treatment difference in exercise duration (MK-0974 - Placebo) \>= -60 seconds. | Amendment 3 of the protocol reduced the dose of telcagepant to be administered from a single dose of 900 mg to a single dose of 600 mg. Pooled data from both the 600-mg and the 900-mg group wiil be utilized in the analyses. Also due to supply issues regarding the 300 mg telcagepant capsules, 280 mg telcagepant tablets with demonstrated bioequivalence to the 300 mg telcagepant capsules, could be administered to participants enrolled after the implementation of Amendment 3. | Angina Pectoris Coronary Heart Disease Calcitonin Gene-related Peptide Receptor | angina pectoris coronary artery disease calcitonin gene-related peptide exercise tolerance, | null | 2 | arm 1: Participants receive single oral dose of 600 mg (two 300 mg capsules or two bioequivalent 280 mg tablets) or 900 mg telcagepant (three 300 mg capsules) in Period 1 and single oral dose of two capsules or tablets of placebo for telcagepant (or three capsules of placebo for telcagepant) in Period 2 of the crossover. Each treatment period is separated by a washout of 96-240 hours. arm 2: Participants receive single oral dose of two capsules or tablets of placebo for telcagepant (or three capsules of placebo for telcagepant) in Period 1 and a single oral dose of 600 mg (two 300 mg capsules or two bioequivalent 280 mg tablets) or 900 mg telcagepant (three 300 mg capsules) in Period 2 of the crossover. Each treatment period is separated by a washout of 96-240 hours. | [
0,
0
] | 2 | [
0,
0
] | intervention 1: None intervention 2: None | intervention 1: telcagepant intervention 2: Placebo to telcagepant | 0 | null | 124 | 0 | 0 | 0 | NCT01294709 | 1COMPLETED | 2009-03-13 | 2008-02-12 | Merck Sharp & Dohme LLC | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 2 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | false | RATIONALE: Monoclonal antibodies, such as RAV12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving RAV12 together with gemcitabine may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects and best dose of monoclonal antibody RAV12 when given together with gemcitabine in treating patients with metastatic pancreatic cancer. | OBJECTIVES:
* To determine the maximum tolerated dose of monoclonal antibody RAV12 when administered with standard gemcitabine hydrochloride in patients with previously untreated metastatic pancreatic cancer.
* To determine the proportion of these patients surviving at 8 months after initiation of this regimen.
* To provide point estimates for response rate and duration of response in patients treated with this regimen.
* To define the toxicity profile of this drug in these patients when administered with standard gemcitabine hydrochloride.
* To estimate, preliminarily, the progression-free survival and overall survival of these patients after treatment with this regimen.
* To explore the utility of the tumor marker, carbohydrate antigen 19-9 (CA19-9), in the assessment of these patients.
OUTLINE: This is a dose-escalation study of monoclonal antibody RAV12, followed by an efficacy study. The study is conducted in two segments.
* Segment 1 (dose escalation of RAV12): Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, and 22 of course 1 and on days 1, 8, and 15 of each subsequent course. Patients also receive RAV12 IV once weekly on days 1, 8, and 15 or twice weekly on days 1, 4 or 5, 8, 11 or 12, 15, and 18 or 19 until the maximum tolerated dose (MTD) is reached. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
* Segment 2 (efficacy): Once the MTD has been determined, patients receive RAV12 at the MTD and gemcitabine hydrochloride as in segment 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are obtained for pharmacokinetic sampling during the dose-escalation segment of the study. Samples are analyzed to determine plasma concentrations of RAV12, gemcitabine hydrochloride, and difluorodeoxyuridine. Blood samples are also examined periodically for expression of serum biomarkers (i.e., CA19-9, RAAG12, and HACA) and for DNA analysis of Fc-gamma receptor polymorphisms. Archival paraffin blocks or slides from biopsy of primary or metastatic deposit or fresh/frozen tissue may be obtained at baseline for additional correlative studies. Samples are analyzed by immunohistochemistry (IHC) for expression of RAAG12 and for development of a companion RAAG12 diagnostic assay.
After completion of study therapy, patients are followed every 8 weeks for up to 3 years.
PROJECTED ACCRUAL: This study will accrue a total of 18 patients in the dose-escalation segment and 63 patients in the efficacy segment of the trial. | Pancreatic Cancer | adenocarcinoma of the pancreas stage IV pancreatic cancer recurrent pancreatic cancer | null | 1 | arm 1: None | [
0
] | 2 | [
2,
0
] | intervention 1: RAV12 at 0.375 mg/kg weekly escalated to 0.75 mg/kg weekly, intravenously. intervention 2: 1000 mg/m2 weekly, intravenously | intervention 1: RAV12 intervention 2: Gemcitabine | 2 | South San Francisco | California | United States | -122.40775 | 37.65466
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238 | 2 | 0 | 0 | 0 | NCT00625586 | 6TERMINATED | 2009-03-18 | 2008-04-15 | MacroGenics | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 1,468 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | true | Rosiglitazone (RSG) has been tested in clinical studies and is approved by the FDA as a treatment for type II diabetes mellitus, a disease that occurs when the body is unable to effectively use glucose. RSG XR, the investigational drug used in this study, is an extended-release form of RSG.
This study tests whether RSG XR safely provides clinical benefit to people with mild to moderate Alzheimer's disease (AD) when combined with one of the currently approved AD medications, Aricept®, Razadyne® or Exelon®. RSG XR is a new approach to AD therapy and this study tests a new way to treat AD by testing whether one's genetic makeup affects the response to the study drug. Clinical data suggesting that RSG may benefit AD patients was first seen in a small study performed at the University of Washington and then from a larger GSK study conducted in Europe and New Zealand. In the first study, subjects receiving RSG once daily for 6 months scored significantly better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that appeared to benefit most from treatment with RSG XR had a specific genetic pattern. They did not have the gene that caused them to produce the protein apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene, instead of APOE e4, from one of their parents. Subjects with one copy of the APOE e4 gene remained at their same level of thinking ability while those with two copies of the APOE e4 gene, continued to worsen during the 6-month treatment. The current study will more directly test the effectiveness or RSG XR on people who either have or lack the APOE e4 gene. | A 54-week, double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to acetylcholinesterase inhibitors on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease (REFLECT-3) | Alzheimer's Disease | adjunctive therapy moderate Alzheimer's disease apolipoprotein E mild rosiglitazone cognition | null | 3 | arm 1: Rosiglitazone Extended Release 2mg OD arm 2: Rosiglitazone Extended Release 8mg OD arm 3: Placebo | [
0,
0,
2
] | 3 | [
0,
0,
10
] | intervention 1: Rosiglitazone Extended Release 2mg OD intervention 2: Rosiglitazone Extended Release 8mg OD intervention 3: Placebo | intervention 1: Rosiglitazone Extended Release 2mg intervention 2: Rosiglitazone Extended Release 8mg intervention 3: Placebo | 194 | Sun City | Arizona | United States | -112.27182 | 33.59754
Tucson | Arizona | United States | -110.92648 | 32.22174
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Laguna Hills | California | United States | -117.71283 | 33.61252
Redlands | California | United States | -117.18254 | 34.05557
San Diego | California | United States | -117.16472 | 32.71571
San Francisco | California | United States | -122.41942 | 37.77493
Norwalk | Connecticut | United States | -73.4079 | 41.1176
Deerfield Beach | Florida | United States | -80.09977 | 26.31841
Delray Beach | Florida | United States | -80.07282 | 26.46146
Fort Lauderdale | Florida | United States | -80.14338 | 26.12231
Hialeah | Florida | United States | -80.27811 | 25.8576
Ocala | Florida | United States | -82.14009 | 29.1872
St. Petersburg | Florida | United States | -82.67927 | 27.77086
Tampa | Florida | United States | -82.45843 | 27.94752
Decatur | Georgia | United States | -84.29631 | 33.77483
Chicago | Illinois | United States | -87.65005 | 41.85003
Springfield | Massachusetts | United States | -72.58981 | 42.10148
West Yarmouth | Massachusetts | United States | -70.24113 | 41.65011
Eatontown | New Jersey | United States | -74.05097 | 40.29622
Toms River | New Jersey | United States | -74.19792 | 39.95373
Whiting | New Jersey | United States | -74.37848 | 39.95456
Amherst | New York | United States | -78.79976 | 42.97839
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Rochester | New York | United States | -77.61556 | 43.15478
Syracuse | New York | United States | -76.14742 | 43.04812
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Centerville | Ohio | United States | -84.15938 | 39.62839
Columbus | Ohio | United States | -82.99879 | 39.96118
Toledo | Ohio | United States | -83.55521 | 41.66394
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Jenkintown | Pennsylvania | United States | -75.12517 | 40.09594
Norristown | Pennsylvania | United States | -75.3399 | 40.1215
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
East Providence | Rhode Island | United States | -71.37005 | 41.81371
Providence | Rhode Island | United States | -71.41283 | 41.82399
Greer | South Carolina | United States | -82.22706 | 34.93873
San Antonio | Texas | United States | -98.49363 | 29.42412
Wichita Falls | Texas | United States | -98.49339 | 33.91371
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Charlottesville | Virginia | United States | -78.47668 | 38.02931
Seattle | Washington | United States | -122.33207 | 47.60621
Middleton | Wisconsin | United States | -89.50429 | 43.09722
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Hornsby | New South Wales | Australia | 151.09931 | -33.70244
Randwick | New South Wales | Australia | 151.24895 | -33.91439
Auchenflower | Queensland | Australia | 152.99213 | -27.47443
Chermside | Queensland | Australia | 153.03062 | -27.38472
Kippa-Ring | Queensland | Australia | 153.0835 | -27.22586
Adelaide | South Australia | Australia | 138.59863 | -34.92866
Woodville | South Australia | Australia | 138.54291 | -34.877
Cheltenham | Victoria | Australia | 145.04806 | -37.96944
Heidelberg West | Victoria | Australia | 145.04034 | -37.73922
Kew | Victoria | Australia | 145.03086 | -37.80639
Nedlands | Western Australia | Australia | 115.8073 | -31.98184
Brussels | N/A | Belgium | 4.34878 | 50.85045
Kortrijk | N/A | Belgium | 3.26487 | 50.82803
Leuven | N/A | Belgium | 4.70093 | 50.87959
Woluwe-Saint-Lambert | N/A | Belgium | 4.42912 | 50.84389
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Varna | N/A | Bulgaria | 27.91667 | 43.21667
Kelowna | British Columbia | Canada | -119.48568 | 49.88307
Saint John | New Brunswick | Canada | -66.05616 | 45.27076
Kentville | Nova Scotia | Canada | -64.49605 | 45.0771
Kingston | Ontario | Canada | -76.48098 | 44.22976
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Peterborough | Ontario | Canada | -78.31623 | 44.30012
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Greenfield Park | Quebec | Canada | -73.46223 | 45.48649
Mirabel | Quebec | Canada | -74.08251 | 45.65008
Montreal | Quebec | Canada | -73.58781 | 45.50884
Sherbrooke | Quebec | Canada | -71.89908 | 45.40008
Québec | N/A | Canada | -71.21454 | 46.81228
Olomouc | N/A | Czechia | 17.25175 | 49.59552
Prague | N/A | Czechia | 14.42076 | 50.08804
Prague | N/A | Czechia | 14.42076 | 50.08804
Trutnov | N/A | Czechia | 15.9127 | 50.56101
Helsinki | N/A | Finland | 24.93545 | 60.16952
Joensuu | N/A | Finland | 29.76316 | 62.60118
Kuopio | N/A | Finland | 27.67703 | 62.89238
Bordeaux | N/A | France | -0.5805 | 44.84044
La Chapelle-sur-Erdre | N/A | France | -1.55239 | 47.29964
La Seyne-sur-Mer | N/A | France | 5.87816 | 43.10322
Lille | N/A | France | 3.05858 | 50.63297
Limoges | N/A | France | 1.24759 | 45.83362
Metz | N/A | France | 6.17269 | 49.11911
Nantes | N/A | France | -1.55336 | 47.21725
Nantes | N/A | France | -1.55336 | 47.21725
Paris | N/A | France | 2.3488 | 48.85341
Sautron | N/A | France | -1.67222 | 47.26345
Toulon | N/A | France | 5.92836 | 43.12442
Toulouse | N/A | France | 1.44367 | 43.60426
Valence | N/A | France | 4.90956 | 44.9256
Aalen | Baden-Wurttemberg | Germany | 10.0933 | 48.83777
Calw | Baden-Wurttemberg | Germany | 8.74031 | 48.71419
Ellwangen | Baden-Wurttemberg | Germany | 10.13173 | 48.96164
Ludwigsburg | Baden-Wurttemberg | Germany | 9.19161 | 48.89731
Stuttgart | Baden-Wurttemberg | Germany | 9.17702 | 48.78232
Tübingen | Baden-Wurttemberg | Germany | 9.05222 | 48.52266
Ulm | Baden-Wurttemberg | Germany | 9.99155 | 48.39841
Ulm | Baden-Wurttemberg | Germany | 9.99155 | 48.39841
Wiesloch | Baden-Wurttemberg | Germany | 8.69846 | 49.29504
Alzenau in Unterfranken | Bavaria | Germany | 9.06455 | 50.0888
Munich | Bavaria | Germany | 11.57549 | 48.13743
Unterhaching | Bavaria | Germany | 11.61564 | 48.06598
Bad Saarow | Brandenburg | Germany | 14.06667 | 52.28333
Bad Homburg | Hesse | Germany | 8.61816 | 50.22683
Erbach im Odenwald | Hesse | Germany | 8.99402 | 49.66148
Chemnitz | Saxony | Germany | 12.92922 | 50.8357
Dresden | Saxony | Germany | 13.73832 | 51.05089
Dresden | Saxony | Germany | 13.73832 | 51.05089
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Gera | Thuringia | Germany | 12.08187 | 50.88029
Jena | Thuringia | Germany | 11.5899 | 50.92878
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Hong Kong | N/A | Hong Kong | 114.17469 | 22.27832
Shatin | N/A | Hong Kong | 114.18333 | 22.38333
Bandar Tun Razak, Cheras | N/A | Malaysia | N/A | N/A
Bandar Tun Razak, Cheras | N/A | Malaysia | N/A | N/A
Ipoh | N/A | Malaysia | 101.0829 | 4.5841
Kelantan | N/A | Malaysia | N/A | N/A
's-Hertogenbosch | N/A | Netherlands | 5.30417 | 51.69917
Alkmaar | N/A | Netherlands | 4.74861 | 52.63167
Blaricum | N/A | Netherlands | 5.24167 | 52.2725
Hengelo | N/A | Netherlands | 6.79306 | 52.26583
Hilversum | N/A | Netherlands | 5.17639 | 52.22333
The Hague | N/A | Netherlands | 4.29861 | 52.07667
Manila | N/A | Philippines | 120.9822 | 14.6042
Pasig | N/A | Philippines | 121.0614 | 14.58691
Bydgoszcz | N/A | Poland | 18.00762 | 53.1235
Krakow | N/A | Poland | 19.93658 | 50.06143
Torun | N/A | Poland | 18.59814 | 53.01375
Warsaw | N/A | Poland | 21.01178 | 52.22977
Singapore | N/A | Singapore | 103.85007 | 1.28967
Singapore | N/A | Singapore | 103.85007 | 1.28967
Singapore | N/A | Singapore | 103.85007 | 1.28967
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Košice | N/A | Slovakia | 21.25808 | 48.71395
Ljubljana | N/A | Slovenia | 14.50513 | 46.05108
Šempeter v Savinj. Dolini | N/A | Slovenia | 15.12194 | 46.25639
Loeventstein | N/A | South Africa | N/A | N/A
Oakdale | N/A | South Africa | 18.63653 | -33.88906
Richards Bay | N/A | South Africa | 32.03768 | -28.78301
Rosebank | N/A | South Africa | 18.47417 | -33.95556
Somerset West | N/A | South Africa | 18.82113 | -34.08401
Waverley, Bloemfontein | N/A | South Africa | N/A | N/A
Willows, X14, Pretoria | N/A | South Africa | N/A | N/A
Seongnam-si | N/A | South Korea | 127.13778 | 37.43861
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Baracaldo/Vizcaya | N/A | Spain | N/A | N/A
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Palma de Mallorca | N/A | Spain | 2.65024 | 39.56939
Tarrasa, Barcelona | N/A | Spain | 2.15899 | 41.38879
Falköping | N/A | Sweden | 13.55068 | 58.17347
Jönköping | N/A | Sweden | 14.15618 | 57.78145
Kalix | N/A | Sweden | 23.15645 | 65.85298
Mölndal | N/A | Sweden | 12.01378 | 57.6554
Sundsvall | N/A | Sweden | 17.3063 | 62.39129
Umeå | N/A | Sweden | 20.25972 | 63.82842
Blackpool | Lancashire | United Kingdom | -3.05 | 53.81667
Bradford | N/A | United Kingdom | -1.75206 | 53.79391
Liverpool | N/A | United Kingdom | -2.97794 | 53.41058
Stirling | N/A | United Kingdom | -3.93682 | 56.11903
West End, Southampton | N/A | United Kingdom | N/A | N/A
West of Scotland Science Park, Glasgow | N/A | United Kingdom | -4.25763 | 55.86515 | 1,468 | 0 | 0 | 0 | NCT00348140 | 1COMPLETED | 2009-03-20 | 2006-07-12 | GlaxoSmithKline | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 12 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | true | 2MALE | false | The proposed study will be a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder. The initial dose depending on the weight of the patient will be as follows: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). For the first two weeks of the study, the dose will be flexible based on response and tolerance and thereafter will remain fixed. | The use of atypical antipsychotics in children began in 1992 with several small case series with clozapine. Since that time, five other atypical agents, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole have been introduced into the US market. The newer atypical agents are not associated with agranulocytosis that has limited the usefulness of clozapine. Among the atypical antipsychotics, risperidone has remained the most extensively studied in children and adolescents, for a variety of problems, including Tourette's disorder, conduct disorder, schizophrenia, aggression, and pervasive development disorder. Risperidone has been shown to be an effective treatment in many of these disorders. However, weight gain, hyperprolactinemia, and extrapyramidal symptoms (EPS) are troublesome adverse effects more commonly associated with risperidone such that the drug's utility in this aged patient population is limited. We expect that the utility of aripiprazole in treating the pediatric population will not be limited by adverse effects like the other atypical antipsychotics. | Conduct Disorder | Aripiprazole | ICF_002.pdf:
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INFORMED CONSENT DOCUMENT
Project Title:
An Open Label Trial of Aripiprazole in the Treatment of Conduct Disorder in
Adolescents
Research Team: Samuel Kuperman, MD, Chadi Calarge, MD, Anne Kolar, MD,
Timothy Holman, MA
• If you are the parent/guardian of a child under 18 years old who is being invited to be in this study,
the word “you” in this document refers to your child. You will be asked to read and sign this
document to give permission for your child to participate.
• If you are a teenager reading this document because you are being invited to be in this study, the
word “you” in this document refers to you. You will be asked to read and sign this document to
indicate your willingness to participate.
This consent form describes the research study to help you decide if you want to participate. This form
provides important information about what you will be asked to do during the study, about the risks and
benefits of the study, and about your rights as a research subject.
• If you have any questions about or do not understand something in this form, you should ask
the research team for more information.
• You should discuss your participation with anyone you choose such as family or friends.
• Do not sign this form unless the study research team has answered your questions and you
decide that you want to be part of this study.
WHAT IS THE PURPOSE OF THIS STUDY?
This is a research study. We are inviting you to participate in this research study because you are a male
between the ages of 13 and 17 and have been diagnosed with Conduct Disorder.
The purpose of this research study is to evaluate the safety and effectiveness of a drug called
aripiprazole as a treatment for conduct disorder. Aripiprazole was recently approved by the US Food
and Drug Administration (FDA) for use in adults as a treatment for psychotic disorders. However, it has
not been approved for use in people under the age of 18 or as a treatment for conduct disorder.
Therefore it is considered investigational.
HOW MANY PEOPLE WILL PARTICIPATE?
Approximately 20 people will take part in this study at the University of Iowa
HOW LONG WILL I BE IN THIS STUDY?
If you agree to take part in this study, your involvement will last for to 7 weeks. If you complete the
study there will be a total of 6 visits. Each of the first 5 visits will last about one hour. The last visit
will last about 2 hours. The second, third and fourth visits will be weekly. The fifth visit will be 2
weeks after the fourth visit. The final visit will be 2 weeks after the fifth visit.
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WHAT WILL HAPPEN DURING THIS STUDY?
The first thing that will happen in this study is the study doctor will perform a physical examination and
discuss your medical and psychiatric history with you. Your vital signs (blood pressure and pulse) will
be recorded. Measurements of your height, weight, and the distance around your waist, hips and arms
will be recorded in order to calculate your body mass index (BMI). A blood sample will be taken for
routine tests and you will be required to provide a urine sample for drugs of abuse testing. You will also
have an electro-cardiogram (ECG), which is a routine heart test. All of these tests are to make sure you
don’t have a physical problem that would prevent you from taking part in the rest of the study.
If you are eligible to continue in the study you will be invited back for a second visit. This is called the
“baseline” visit. Your vital signs and BMI will again be recorded. The study doctor and one of the
other investigators will interview you about your symptoms of Conduct Disorder. Medication side
effect ratings will be also be done. One of your parents or guardians will also be asked to fill out 3
questionnaires about your symptoms. All of the information at the baseline visit is to determine your
level of functioning before your first dose of aripiprazole. At the end of this visit aripiprazole will be
dispensed to you. The study doctor will explain how and when to take the medication.
One week later you will return for the third visit. Your vital signs and BMI will again be recorded. The
study doctor and one of the other investigators will interview you about your symptoms of Conduct
Disorder. Medication side effect ratings will be also be done. One of your parents or guardians will
again be asked to fill out 3 questionnaires about your symptoms. The aripiprazole dose may be increased
at this visit, depending on whether you report any side effects from the medication.
One week later you will return for a fourth visit. Your vital signs and BMI will again be recorded. The
study doctor and one of the other investigators will interview you about your symptoms of Conduct
Disorder. Medication side effect ratings will be again be done. One of your parents or guardians will
again be asked to fill out 3 questionnaires about your symptoms. The aripiprazole dose may again be
increased at this visit, or decreased depending on whether you report any side effects from the
medication.
Two weeks later you will return for a fifth visit. All of the things that were done at the fourth visit will
be repeated. The aripiprazole dose may again be increased at this visit, or decreased depending on
whether you report any side effects from the medication.
Two weeks later you will return for the sixth and final visit. The study doctor will repeat the physical
examination that was performed at the first visit. An ECG will be repeated. Blood will be collected for
routine laboratory tests. Urine will be collected for drugs of abuse testing. Your vital signs and BMI
will again be recorded. The study doctor and one of the other investigators will interview you about
your symptoms of conduct disorder. Medication side effect ratings will be also be done. One of your
parents or guardians will again be asked to fill out 3 questionnaires about your symptoms. The study
doctor will discuss with you and at least one of your parents or guardians whether you should continue
to take aripiprazole. He will also discuss alternative treatments, if applicable. The schedule of events
for the study is summarized in the following table:
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Procedure
Screening visit
baseline week 1 week 2 week 4 week 6
Time until next visit
2-7 days
7 days
7days
14 days 14 days
Physical Exam
X
X
ECG
X
X
Vitals, Height, Weight, BMI
X
X
X
X
X
X
Urine Collection
X
X
Blood collection
X
X
Interview with study doctor
X
X
X
X
X
X
Interview with study team
X
X
X
X
X
Parent/Guardian questionnaires
X
X
X
X
X
WHAT ARE THE RISKS OF THIS STUDY?
There may be some risks from being in this study. The most common side effects seen with aripiprazole
in adults were headache, feeling slowed down, fever, upset stomach, vomiting, constipation, anxiety,
trouble sleeping, lightheadedness, sleepiness, restlessness, tremor, cold symptoms, coughing, rash and
blurred vision.
Blood collection involves a needle stick that may cause pain, bleeding, bruising, fainting and in rare
cases an infection.
The interviews and questionnaires may cause emotional discomfort. You are free not to answer
questions that cause discomfort.
Are there any Unforeseen Risks?
In addition to the risks described above, there may be unknown risks, or risks that we did not anticipate,
associated with being in this study. Aripiprazole is not approved by the FDA for use in people under the
age of 18 or for people with Conduct Disorder. Information about the use of aripiprazole in people
under the age of 18 is limited.
WHAT ARE THE BENEFITS OF THIS STUDY?
We don’t know if you will benefit from being in this study. However, we hope that, in the future, other
people might benefit from this study because of knowledge gained by the investigators about the use of
aripiprazole in people age 13 to 17 with Conduct Disorder.
WHAT OTHER TREATMENT OPTIONS ARE THERE?
Before you decide whether or not to be in this study, your doctor will discuss the other options that are
available to you. Instead of being in this study, you could receive counseling; take other medications, or
both.
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WILL IT COST ME ANYTHING TO BE IN THIS STUDY?
You will not have any costs for being in this research study. You and/or your medical/hospital insurance
carrier will remain responsible for your regular medical care expenses.
WILL I BE PAID FOR PARTICIPATING?
You will be paid for being in this research study. You will be paid $50 for each completed visit.
Payment will be by a check issued by the University of Iowa in the name of the minor participant (the
person who actually receives the study drug), not the parent or guardian. It usually takes 1 to 2 weeks
after a visit before you receive payment. If you complete all 6 visits the total payment will be $300.
You will need to provide your social security number (SSN) in order for us to pay you. You may also
need to provide your address if a check will be mailed to you.
WHO IS FUNDING THIS STUDY?
Bristol-Myers Squibb Co. is funding this research study. Bristol-Myers Squibb Co. is the drug company
that makes aripiprazole. This means that the University of Iowa is receiving payments from Bristol-
Myers Squibb Co. to support the activities that are required to conduct the study. No one on the
research team will receive a direct payment or an increase in salary from for conducting this study.
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY?
• If you are injured or become ill from taking part in this study, medical treatment is available at the
University of Iowa Hospitals and Clinics.
• No compensation for treatment of research-related illness or injury is available from the University
of Iowa unless it is proven to be the direct result of negligence by a University employee.
• If you experience a research-related illness or injury, sustained from the administration of the study
drugs in accordance with the protocol, sponsor, BMS will pay for the all hospital and medical costs
required for diagnosis and treatment provided that such costs are not covered by any third party or
governmental programs providing such coverage.
WHAT ABOUT CONFIDENTIALITY?
We will keep your participation in this research study confidential to the extent permitted by law.
However, it is possible that other people may become aware of your participation in this study. For
example, federal government regulatory agencies, the U.S. Food and Drug Administration, Bristol-
Myers, Squibb Co. auditing departments of the University of Iowa and the University of Iowa
Institutional Review Board (a committee that reviews and approves research studies) may inspect and
copy records pertaining to this research. Some of these records could contain information that
personally identifies you.
In the future, Bristol-Myers Squibb Co. may continue to use your health information that is collected as
part of this study. For example, Bristol-Myers Squibb Co. may combine information from this study
with the results of other studies to re-analyze the safety and effectiveness of the study medication, to
evaluate other products or therapies, to develop a better understanding of a disease, or to improve the
design of future research studies. Bristol-Myers Squibb Co. may also share information from the study
with regulatory agencies in foreign countries.
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To help protect your confidentiality, we will include replacing your name on the interview forms with a
5-digit number, storing records in a locked file cabinet in a locked room in a building with access
limited to members of the study team, and storing electronic records on computers that are protected
with passwords. Laboratory reports, ECG reports and doctor’s notes will be placed in your hospital
chart. If we write a report or article about this study or share the study data set with others, we will do
so in such a way that you cannot be directly identified.
We are taking some special steps to protect your confidentiality. The University of Iowa Hospitals and
Clinics generally requires that we put a copy of this Informed Consent Document in your medical record
chart. Instead of doing that, we’ll ask you to sign another form, called a Record of Consent, which gives
no specific information about this study. The Record of Consent will be placed in your medical record
chart. We will keep this Informed Consent Document in our research files; it will not be placed in your
medical record chart.
To further protect your privacy, the researchers have obtained a Certificate of Confidentiality from the
Department of Health and Human Services (DHHS). This Certificate means that the researchers cannot
be forced (for example by court subpoena) to disclose information that may identify you in any federal,
state, or local civil, criminal, administrative, legislative, or other proceeding. However, a Certificate of
Confidentiality does not prohibit the researcher from disclosing information about you or your
involvement in this research that you have agreed to disclose or make available. For example, if you or
your legally authorized representative request in writing that information about you or your participation
in the research be released to an insurance company, the researcher may not use the Certificate of
Confidentiality to withhold this information. This means that you and your family should actively
protect your own privacy. Finally, the researcher is not prevented from taking steps, including reporting
to appropriate authorities, to prevent serious harm to yourself or others. You may receive a copy of the
Certificate of Confidentiality upon request.
WILL MY HEALTH INFORMATION BE USED DURING THIS STUDY?
The Federal Health Insurance Portability and Accountability Act (HIPAA) requires your health care
provider to obtain your permission for the research team to access or create “protected health
information” about you for purposes of this research study. Protected health information is information
that personally identifies you and relates to your past, present, or future physical or mental health
condition or care. We will access or create health information about you, as described in this document,
for purposes of this research study and for your treatment. Once your health care provider has disclosed
your protected health information to us, it may no longer be protected by the Federal HIPAA privacy
regulations, but we will continue to protect your confidentiality as described under “Confidentiality.”
We may share your health information related to this study with other parties including federal
government regulatory agencies, the University of Iowa Institutional Review Boards and support staff,
and Bristol-Myers Squibb Co.
You cannot participate in this study unless you permit us to use your protected health information. If
you choose not to allow us to use your protected health information, we will discuss any non-research
alternatives available to you. Your decision will not affect your right to medical care that is not
research-related. Your signature on this Consent Document authorizes your health care provider to give
us permission to use or create health information about you.
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Although you may not be allowed to see study information until after this study is over, you may be
given access to your health care records by contacting your health care provider. Your permission for us
to access or create protected health information about you for purposes of this study has no expiration
date. You may withdraw your permission for us to use your health information for this research study by
sending a written notice to Samuel Kuperman, M.D., 1873 JPP, University of Iowa, Iowa City, Iowa
52242. However, we may still use your health information that was collected before withdrawing your
permission. Also, if we have sent your health information to a third party, such as the study sponsor, or
we have removed your identifying information, it may not be possible to prevent its future use. You will
receive a copy of this signed document.
IS BEING IN THIS STUDY VOLUNTARY?
Taking part in this research study is completely voluntary. You may choose not to take part at all. If
you decide to be in this study, you may stop participating at any time. If you decide not to be in this
study, or if you stop participating at any time, you won’t be penalized or lose any benefits for which you
otherwise qualify.
What if I Decide to Drop Out of the Study?
If you decide to leave the study early, we will ask you to return for a close out visit in which we will
conduct all the safety testing and interviews that are scheduled at the final visit. If you choose not to
have the safety testing it won’t be possible for the study team to know whether you had any bad effects
from taking part in the study. You also would be expected to return all un-used study drug at the end of
the study or if you choose to stop the study early.
Will I Receive New Information About the Study while Participating?
If we obtain any new information during this study that might affect your willingness to continue
participating in the study, we’ll promptly provide you with that information.
Can Someone Else End my Participation in this Study?
Under certain circumstances, the researchers or the study sponsor might decide to end your participation
in this research study earlier than planned. This might happen because the sponsor stops funding the
study. This might also happen because the study doctor feels it would not be safe for you to continue or
because you experience side effects.
WHAT IF I HAVE QUESTIONS?
We encourage you to ask questions. If you have any questions about the research study itself, please
contact: Samuel Kuperman, M.D. at 319-356-1482, Anne Kolar, M.D. at 319-356-1182 or Chadi
Calarge, M.D. at 319-335-8771. If you have a problem during evening or weekend hours that you feel
needs immediate medical attention and neither Dr. Kuperman nor Dr. Kolar nor Dr. Calarge are
available, you should go to the nearest emergency room. The University of Iowa Healthcare general
number is 319-356-1616. You can ask to speak with the psychiatric resident (who is a medical doctor)
on call.
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If you have questions, concerns, or complaints about your rights as a research subject or about research
related injury, please contact the Human Subjects Office, 340 College of Medicine Administration
Building, The University of Iowa, Iowa City, Iowa, 52242, (319) 335-6564, or e-mail irb@uiowa.edu.
General information about being a research subject can be found by clicking “Info for Public” on the
Human Subjects Office web site, http://research.uiowa.edu/hso.
This Informed Consent Document is not a contract. It is a written explanation of what will happen
during the study if you decide to participate. You are not waiving any legal rights by signing this
Informed Consent Document. Your signature indicates that this research study has been explained to
you, that your questions have been answered, and that you agree to take part in this study. You will
receive a copy of this form.
Subject's Name (printed): __________________________________________________________
__________________________________________
_______________________________
(Signature of Subject)
(Date)
Parent/Guardian or Legally Authorized Representative’s Name and Relationship to Subject:
__________________________________________
_______________________________
(Name - printed)
(Relationship to Subject - printed)
__________________________________________
_______________________________
(Signature of Parent/Guardian or
(Date)
Legally Authorized Representative)
Statement of Person Who Obtained Consent
I have discussed the above points with the subject or, where appropriate, with the subject’s legally
authorized representative. It is my opinion that the subject understands the risks, benefits, and
procedures involved with participation in this research study.
__________________________________________
_______________________________
(Signature of Person who Obtained Consent)
(Date)
Prot_000.pdf:
PROTOCOL: An Open Label Trial of Aripiprazole in the Treatment of Conduct
Disorder in Adolescents.
Rationale:
The use of atypical antipsychotics in children began in 1992 with several small
case series with clozapine. Since that time, five other atypical agents, risperidone,
olanzapine, quetiapine, ziprasidone and aripiprazole have been introduced into the US
market. The newer atypical agents are not associated with agranulocytosis that has
limited the usefulness of clozapine. Among the atypical antipsychotics, risperidone has
remained the most extensively studied in children and adolescents, for a variety of
problems, including Tourette’s disorder, conduct disorder, schizophrenia, aggression, and
pervasive development disorder. Risperidone has been shown to be an effective
treatment in many of these disorders. However, weight gain, hyperprolactinemia, and
extrapyramidal symptoms (EPS) are troublesome adverse effects more commonly
associated with risperidone such that the drug’s utility in this aged patient population is
limited. We expect that the utility of aripiprazole in treating the pediatric population will
not be limited by adverse effects like the other atypical antipsychotics.
Previous Work:
Several small studies have found risperidone to be more effective than placebo in
treating children and adolescents with either aggression or conduct disorder. In a 10-
week, randomized, double-blind study (n=20), risperidone was superior to placebo in
reducing most measures of the Rating of Aggression Against People and/or Property
Scale (RAAPP), when dosed at an average of 0.028mg/kg/day [range = 0.75-1.50
mg/day] (Findling et al 2000). The data also suggested that treatment with risperidone
was associated with weight gain. The predicted weight gain from a repeated measures
analysis for the risperidone group of 4.2±0.7kg was greater than the placebo group
(p=0.003). There was no difference in the incidence of EPS at endpoint according the
Simpson-Angus EPS (SAEPS) rating scale.
Buitelaar et al (2001) assessed the efficacy of risperidone in the treatment of
aggression. Thirty-eight adolescents were randomized to either risperidone or placebo in
a double-blind fashion. The mean daily dose of risperidone at end of treatment (6 weeks)
was 2.9mg [range = 1.5-4 mg]. Risperidone treatment produced improvement on the
Clinical Global Impression-Severity (CGI-S) scale (LOCF, p<0.001) and the at-school
Aberrant Behavior Checklist (ABC) overall and hyperactivity scales (p<0.05). In the
risperidone group, following a 2-week washout following the 6-week trial worsening on
all efficacy measures (CGI-S, Overt Aggression Scale-Modified (OAS-M), and the ABC.
Weight gain was significant in the risperidone group (3.5% body weight increase, range –
1 to +6kg, p<0.05). Transient tiredness was also noted in 58% of drug-treated subjects,
and was also the reason for dose reduction in five of the drug-treated subjects.
Extrapyramidal Side Effect Rating Scale (ESRS) scores increased for Parkinsonism
(cluster II) at endpoint compared to placebo (p<0.05).
Bellinghen et al (2001) compared risperidone (n=6) to placebo (n=7) in the
treatment of behavioral disturbances in children and adolescents. Thirteen patients were
enrolled in a 4-week double-blind, placebo-controlled study. Risperidone (mean dose =
0.05mg/kg; mean total dose = 1.2 mg/day) was more effective than placebo in improving
ABC cluster scores for irritation and hyperactivity, the CGI scale. No significant
differences in EPS symptoms or weight gain were seen between the treatment groups.
The lack of any adverse effect differences is not surprising considering the low dose of
risperidone and the small number of patients enrolled in the study.
Methods:
Dose and Schedule of Treatment: The proposed study will be a 6-week open label
study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17
years, Tanner Stage 4) diagnosed with conduct disorder. The initial dose depending on
the weight of the patient will be as follows: < 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70
kg = 5 mg/d; > 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter
the dose will be flexible based on response and tolerance.
Main outcome measures: The primary outcome efficacy measures will be the Rating of
Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993), Overt
Aggression Scale-Modified (OAS-M) (Kay et al 1988), and Children’s Aggression Scale-
Parent Version (CAS-P) (Halpern et al 2002) while the secondary outcome measure will
be the CGI severity and improvement scale (NIMH, 1985a). Safety measures for
extrapyramidal adverse effects will include the AIMS (NIMH, 1985b) for tardive
dyskinesia, Barnes Akathisia Scale (Barnes 1989) (BAS) and the Simpson-Angus Scale
(SAS) (Simpson and Angus 1970). The UKU (Lingjaerde et al 1987) will be used for
monitoring non-motor adverse effects. Height, weight and body mass index
measurements as well as initial and endpoint fasting blood sugars and lipids will assess
the effect of weight change. Obtaining serum prolactin levels as well as screening for the
sexual dysfunction adverse effects including galactorrhea, gynecomastia, menstrual
irregularities and changes in libido will assess sexual dysfunction adverse effects. An
initial and endpoint ECG will be obtained to monitor patients for any changes in the QT-
corrected interval. A gamma-GT will be collected to monitor liver function.
Schedule of Events:
Procedure
screening
baseline week 1 week 2 week 4 week 6
(-7 to –28days)
History-Demographics
X
Physical Exam
X
X
ECG
X
X
Vitals, Height, Weight, BMI
X
X
X
X
X
X
Urine Collection
X
X
Phlebotomy
X
X
Dispense Study Drug
X
X
X
X
X
Determine medication compliance
X
X
X
X
Laboratory Tests
fasting glucose
X
X
fasting lipid profile:
total cholesterol
X
X
HDL-cholesterol
X
X
LDL-cholesterol
X
X
Triglicerides
X
X
Prolactin
X
X
Gamma GT
X
X
CBC
X
X
Urine Drugs of Abuse Screen
X
X
Psychiatric Rating Scales
RAAPP
X
X
X
X
X
CAS-P
X
X
X
X
X
OAS
X
X
X
X
X
CGI-S
X
X
X
X
X
CGI-I
X
X
X
X
Side Effect Rating Scales
AIMS
X
X
X
X
X
SAS
X
X
X
X
X
UKU
X
X
X
X
X
BAS
X
X
X
X
X
References:
Buitelaar JK, van der Gaag, R, Cohen-Kettenis P, et al (2001). A randomized controlled
trial of risperidone in the treatment of aggression in hospitalized adolescents with
subaverage cognitive abilities. J Clin Psychiatry 62:239-48.
Barnes TRE (1989). A rating scale for drug-induced akathisia. Br j Psychiatry 154:672-
6.
Data on File, 2003, Bristol-Myers Squibb Company, Princeton, NJ 08536
Kemph JO DeVane CL, Levin GM, et al (1993). Treatment of aggressive children with
clonidine: results of an open pilot study. Am Acad Child Adolesc Psychiatry
32:577-81.
Findling RL, McNamara NK, Branicky L, et al (2000). A double-blind pilot study of
risperidone in the treatment of conduct disorder. J Am Acad Child Adolesc
Psychiatry 39:509-16.
Kay SR, Wolkenfeld F, Murrill LM (1988). Profiles of aggression among psychiatric
patients : I. nature and prevalence. J Nerv Ment Dis 176:539-46.
Lingjaerde O, Ahlfors UG, Bech P, et al (1987). The UKU side effect rating scale. A
new comprehensive rating scale for psychotropic drugs and a cross-section study
of side effect in neuroleptic-treated patient. Acta Psychiatr Scand Suppl 334:1-
100.
National Institute of Mental Health (1985a). CGI (Clinical Global Impression) Scale.
Psychopharmacol Bull 21:839-43.
National Institute of Mental Health (1985b). AIMS (Abnormal Involuntary Movement
Scale). Psychopharmacol Bull 21:839-43.
Simpson GM, Angus JWS (1970). A rating scale for extrapyramidal side effects. Acta
Psychiatr Scand Suppl 212:11-9.
Van Bellinghen M, DeTroch C ( 2001). Risperidone in the treatment of behavior
disturbances in children and adolescents with borderline intellectual functioning:
A double-blind placebo-controlled pilot trial. J Child Adolesc Psychopharmacol
11:5-13.
Budget: Open label Aripiprazole-Conduct Disorder study
Procedure
Screening Baseline Week 1 Week 2 Week 4 Week 6
History-Demographics
50.00
Physical Exam
100.00
100.00
ECG
125.00
125.00
Vitals, Height, Weight, BMI
10.00
10.00
10.00
10.00
10.00
10.00
Urine Collection
5.00
5.00
Phlebotomy
10.00
10.00
Laboratory Tests
Fasting glucose
12.00
12.00
Fasting lipid profile:
Total cholesterol
15.00
15.00
HDL-cholesterol
29.00
29.00
LDL-cholesterol
0.00
0.00
Triglycerides
19.00
19.00
Prolactin
53.00
53.00
Gamma GT
21.00
21.00
CBC
27.00
27.00
Urine Drugs of Abuse Screen
85.00
85.00
Psychiatric Rating Scales
RAAPP
25.00
25.00
25.00
25.00
25.00
CAS-P
25.00
25.00
25.00
25.00
25.00
OAS
25.00
25.00
25.00
25.00
25.00
CGI-S
25.00
25.00
25.00
25.00
25.00
CGI-I
25.00
25.00
25.00
25.00
25.00
Side Effect Rating Scales
AIMS/BAS/SAS
25.00
25.00
25.00
25.00
25.00
UKU
25.00
25.00
25.00
25.00
25.00
Investigator Fee
100.00
100.00 100.00 100.00 100.00 100.00
Study Coordinator Fee
50.00
50.00
50.00
50.00
50.00
50.00
Subject Compensation
25.00
25.00
25.00
25.00
25.00
25.00
Total direct costs per visit
886.00
360.00 360.00 360.00 360.00 861.00
Total direct costs per completed subject
3187.00
Total indirect costs per visit (25%)
184.00
90.00
90.00
90.00
90.00 215.25
Total indirect costs per completed
subject
759.25
Total costs per completed subject
3796.25
SAP_001.pdf:
All statistical analyses were conducted using InStat 3.1a (GraphPad Software, La Jolla, CA). A modified intent-to-treat (ITT) population was used for analyses.
For each outcome variable, the modified ITT population included all subjects with at least one post-baseline psychometric measurement (subjects received at
least one week of aripiprazole). Demographic data is presented as means and standard deviations while bivariant data were contrasted using paired-t tests. A
repeated measure analysis of variance (ANOVA) model was used to assess the changes in the psychometric tests. In cases where a subject did not complete the
entire 6-week trial, the last available observation was carried forward (LOCF) and used for statistical comparisons. A repeated measure analysis of variance was
used to assess the changes in the psychometric tests. For determining significance of statistical tests 〈 was set at 0.05.
| 1 | arm 1: All subjects were male and had a diagnosis of conduct disorder. All subjects were offered treatment with aripiprazole. | [
5
] | 1 | [
0
] | intervention 1: The initial dose depending on the weight of the patient will be as follows: \< 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; \> 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose will be flexible based on response and tolerance for the duration of the 6 week study. All subjects initially received either a 5 or 10 mg/d (7.0 ± 2.6 mg/d) dose of aripiprazole. Thereafter the dose was individualized based on response and tolerance. Maximum dose was 20 mg. | intervention 1: Aripiprazole | 1 | Iowa City | Iowa | United States | -91.53017 | 41.66113 | 10 | 0 | 0 | 0 | NCT00250705 | 1COMPLETED | 2009-03-23 | 2004-11-17 | University of Iowa | 7OTHER | true | true | true | https://cdn.clinicaltrials.gov/large-docs/05/NCT00250705/Prot_000.pdf https://cdn.clinicaltrials.gov/large-docs/05/NCT00250705/SAP_001.pdf https://cdn.clinicaltrials.gov/large-docs/05/NCT00250705/ICF_002.pdf | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 205 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | true | This randomized phase II trial studies how well giving celecoxib with or without eflornithine works in preventing colorectal cancer in patients with familial adenomatous polyposis. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of celecoxib and eflornithine may keep cancer from forming in patients with familial adenomatous polyposis. | PRIMARY OBJECTIVES:
I. To determine the relative efficacy of celecoxib plus eflornithine (DFMO) versus celecoxib plus DFMO placebo in participants with familial adenomatous polyposis (FAP), as evidenced by the percent change from baseline in the number of polyps in focal area(s) of the colorectum in participants having 5 or more \>= 2mm colorectal polyps with or without duodenal polyps at baseline.
II. To determine the relative tolerability and safety of celecoxib + DFMO in FAP study participants.
SECONDARY OBJECTIVES:
I. To determine the percent change in polyp size in focal area(s) of the colorectum II. To determine the change in global colorectal polyp burden III. To determine the percent change in the area of plaque-like duodenal polyps in participants presenting with duodenal disease at baseline.
IV. To analyze the effects of these agents on the following panel of mucosal biomarkers: antigen identified by monoclonal antibody Ki-67 (Ki-67), mitotic index (number and spatial distribution of mitoses), phosphorylated histone H3, cyclin-dependent kinase inhibitor 1A (p21/WAF1/Cip1), apoptosis (Terminal deoxynucleotidyl transferase dUTP nick end labeling \[TUNEL\]), apoptotic index, BCL2-associated X protein (Bax), B-cell CLL/lymphoma 2 (Bcl-2) and measurement of drug effects in colonic polyp and normal tissue cyclooxygenase (cyclooxygenase-1 \[COX-1\], cyclooxygenase-2 \[COX-2\]) protein levels, prostaglandin E2 (PGE2), ornithine decarboxylase and polyamines.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive celecoxib orally (PO) twice daily (BID) and placebo PO daily.
ARM II: Patients receive celecoxib PO BID and eflornithine PO daily.
In both arms, treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
After completion of just treatment, patients are followed up at 1-2 months. | Colorectal Cancer Familial Adenomatous Polyposis | null | 2 | arm 1: Celecoxib 400 mg orally twice daily (PO BID) and Placebo once a day. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity. arm 2: Celecoxib 400 mg PO BID and Eflornithine PO daily 0.5 g/m\^2/day rounded down to the nearest 250 mg dose. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity. | [
1,
0
] | 5 | [
0,
10,
0,
10,
10
] | intervention 1: Given 400 mg PO twice a day intervention 2: Given PO to match DFMO intervention 3: Given PO at 0.5 gm/m\^2/day rounded down to the nearest 250 mg dose (BSA of \< 1.4 = 500 mg/day; BSA of 1.5 - 2.0 = 750 mg/day; BSA of 2.1 - 2.5 = 1000 mg/day; BSA of \> 2.6 = 1,250 mg/day). intervention 4: Correlative studies intervention 5: Ancillary studies | intervention 1: Celecoxib intervention 2: Placebo intervention 3: eflornithine intervention 4: Laboratory biomarker analysis intervention 5: Questionnaire administration | 1 | Houston | Texas | United States | -95.36327 | 29.76328 | 112 | 0 | 0 | 0 | NCT00033371 | 1COMPLETED | 2009-03-24 | 2001-12-13 | National Cancer Institute (NCI) | 0NIH | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
4
] | 2,336 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | The study is intended to test efficacy, safety and tolerability of two doses of Mirabegron against placebo and compare the efficacy and safety with active comparator in patients with symptoms of overactive bladder. | null | Urinary Bladder, Overactive | Micturition Urinary incontinence Urinary urge incontinence Overactive bladder (OAB) Urgency YM178 Frequency | null | 4 | arm 1: Participants received matching mirabegron placebo tablets and matching tolterodine slow release (SR) placebo capsules orally once a day for 12 weeks. arm 2: Participants received mirabegron 50 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks. arm 3: Participants received mirabegron 100 mg tablets and matching tolterodine SR placebo capsules orally once a day for 12 weeks. arm 4: Participants received tolterodine SR 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 weeks. | [
2,
0,
0,
1
] | 4 | [
0,
0,
0,
0
] | intervention 1: Tablets intervention 2: Capsules intervention 3: Matching mirabegron placebo tablets. intervention 4: Matching tolterodine placebo capsules. | intervention 1: Mirabegron intervention 2: Tolterodine intervention 3: Placebo to Mirabegron intervention 4: Placebo to Tolterodine | 218 | Auchenflower | N/A | Australia | 152.99213 | -27.47443
Clayton | N/A | Australia | 145.11667 | -37.91667
Kogarah | N/A | Australia | 151.13564 | -33.9681
Randwick | N/A | Australia | 151.24895 | -33.91439
Woolloongabba | N/A | Australia | 153.03655 | -27.48855
Graz | N/A | Austria | 15.45 | 47.06667
Innsbruck | N/A | Austria | 11.39454 | 47.26266
Linz | N/A | Austria | 14.28611 | 48.30639
Minsk | N/A | Belarus | 27.56653 | 53.90019
Minsk | N/A | Belarus | 27.56653 | 53.90019
Minsk | N/A | Belarus | 27.56653 | 53.90019
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Edegem | N/A | Belgium | 4.44504 | 51.15662
Ghent | N/A | Belgium | 3.71667 | 51.05
Kortrijk | N/A | Belgium | 3.26487 | 50.82803
Leper | N/A | Belgium | N/A | N/A
Leuven | N/A | Belgium | 4.70093 | 50.87959
Liège | N/A | Belgium | 5.56749 | 50.63373
Sint-Truiden | N/A | Belgium | 5.18647 | 50.81679
Pleven | N/A | Bulgaria | 24.61667 | 43.41667
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Varna | N/A | Bulgaria | 27.91667 | 43.21667
Brno | N/A | Czechia | 16.60796 | 49.19522
Mělník | N/A | Czechia | 14.47411 | 50.3505
Olomouc | N/A | Czechia | 17.25175 | 49.59552
Ostrava-Poruba | N/A | Czechia | N/A | N/A
Pilsen | N/A | Czechia | 13.37759 | 49.74747
Prague | N/A | Czechia | 14.42076 | 50.08804
Prague | N/A | Czechia | 14.42076 | 50.08804
Prague | N/A | Czechia | 14.42076 | 50.08804
Štětí | N/A | Czechia | 14.37421 | 50.45298
Ústí nad Labem | N/A | Czechia | 14.03227 | 50.6607
Aalborg | N/A | Denmark | 9.9187 | 57.048
Aarhus | N/A | Denmark | 10.21076 | 56.15674
Glostrup Municipality | N/A | Denmark | 12.40377 | 55.6666
Roskilde | N/A | Denmark | 12.08035 | 55.64152
Helsinki | N/A | Finland | 24.93545 | 60.16952
Oulu | N/A | Finland | 25.46816 | 65.01236
Tampere | N/A | Finland | 23.78712 | 61.49911
Turku | N/A | Finland | 22.26869 | 60.45148
Bordeaux | N/A | France | -0.5805 | 44.84044
Colmar | N/A | France | 7.35584 | 48.08078
Marseille | N/A | France | 5.38107 | 43.29695
Marseille | N/A | France | 5.38107 | 43.29695
Mulhouse | N/A | France | 7.32866 | 47.75205
Nantes | N/A | France | -1.55336 | 47.21725
Nîmes | N/A | France | 4.35788 | 43.83665
Orléans | N/A | France | 1.90389 | 47.90289
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Rouen | N/A | France | 1.09932 | 49.44313
Saint-Priest-en-Jarez | N/A | France | 4.37678 | 45.4739
Strasbourg | N/A | France | 7.74553 | 48.58392
Toulouse | N/A | France | 1.44367 | 43.60426
Aichach | N/A | Germany | 11.13413 | 48.45755
Bad Ems | N/A | Germany | 7.71369 | 50.33544
Bautzen | N/A | Germany | 14.43494 | 51.18035
Berlin | N/A | Germany | 13.41053 | 52.52437
Duisburg | N/A | Germany | 6.76516 | 51.43247
Eisleben Lutherstadt | N/A | Germany | 11.54835 | 51.52754
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Ganderkesee | N/A | Germany | 8.53333 | 53.03333
Hagenow | N/A | Germany | 11.19159 | 53.43134
Halle | N/A | Germany | 11.97947 | 51.48158
Hamburg | N/A | Germany | 9.99302 | 53.55073
Henningsdorf | N/A | Germany | N/A | N/A
Hettstedt | N/A | Germany | 11.51146 | 51.6503
Koblenz | N/A | Germany | 7.57883 | 50.35357
Leipzig | N/A | Germany | 12.37129 | 51.33962
Muenchen-Bogenhausen | N/A | Germany | N/A | N/A
Neustadt in Sachsen | N/A | Germany | 14.21785 | 51.02844
Oranienburg | N/A | Germany | 13.24197 | 52.75577
Radebeul | N/A | Germany | 13.66047 | 51.10654
Sangerhausen | N/A | Germany | 11.29533 | 51.47221
Trier | N/A | Germany | 6.63935 | 49.75565
Uetersen | N/A | Germany | 9.66197 | 53.68878
Athens | N/A | Greece | 23.72784 | 37.98376
Nikaias-Piraeus | N/A | Greece | N/A | N/A
Pátrai | N/A | Greece | 21.73444 | 38.24444
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Debrecen | N/A | Hungary | 21.62444 | 47.53167
Eger | N/A | Hungary | 20.37329 | 47.90265
Nyíregyháza | N/A | Hungary | 21.71671 | 47.95539
Pápa | N/A | Hungary | 17.4674 | 47.33004
Sopron | N/A | Hungary | 16.59049 | 47.68501
Szeged | N/A | Hungary | 20.14824 | 46.253
Szekszárd | N/A | Hungary | 18.70905 | 46.35014
Székesfehérvár | N/A | Hungary | 18.41034 | 47.18995
Tatabánya | N/A | Hungary | 18.39325 | 47.58494
Veszprém | N/A | Hungary | 17.91149 | 47.09327
Reykjavik | N/A | Iceland | -21.89541 | 64.13548
Cork | N/A | Ireland | -8.47061 | 51.89797
Dublin | N/A | Ireland | -6.24889 | 53.33306
Mullingar | N/A | Ireland | -7.3385 | 53.52466
Tralee | N/A | Ireland | -9.70264 | 52.27042
Bari | N/A | Italy | 16.86982 | 41.12066
Catanzaro | N/A | Italy | 16.60086 | 38.88247
Florence | N/A | Italy | 11.24626 | 43.77925
Florence | N/A | Italy | 11.24626 | 43.77925
Genoa | N/A | Italy | 8.94439 | 44.40478
Latina | N/A | Italy | 12.9043 | 41.46614
Magenta | N/A | Italy | 8.88453 | 45.46456
Milan | N/A | Italy | 9.18951 | 45.46427
Milan | N/A | Italy | 9.18951 | 45.46427
Modena | N/A | Italy | 10.92539 | 44.64783
Naples | N/A | Italy | 14.26811 | 40.85216
Perugia | N/A | Italy | 12.38878 | 43.1122
Teramo | N/A | Italy | 13.69901 | 42.66123
Treviglio | N/A | Italy | 9.59102 | 45.52081
Varese | N/A | Italy | 8.82511 | 45.82058
Liepāja | N/A | Latvia | 21.01085 | 56.50474
Riga | N/A | Latvia | 24.10589 | 56.946
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Apeldoorn | N/A | Netherlands | 5.96944 | 52.21
Apeldoorn | N/A | Netherlands | 5.96944 | 52.21
Eindhoven | N/A | Netherlands | 5.47778 | 51.44083
Enschede | N/A | Netherlands | 6.89583 | 52.21833
Leiden | N/A | Netherlands | 4.49306 | 52.15833
Maastricht | N/A | Netherlands | 5.68889 | 50.84833
Nijmegen | N/A | Netherlands | 5.85278 | 51.8425
Sneek | N/A | Netherlands | 5.6589 | 53.03297
Tilburg | N/A | Netherlands | 5.0913 | 51.55551
Winterswijk | N/A | Netherlands | 6.71944 | 51.9725
Bergen | N/A | Norway | 5.32415 | 60.39299
Drammen | N/A | Norway | 10.20449 | 59.74389
Hamar | N/A | Norway | 11.06798 | 60.7945
Oslo | N/A | Norway | 10.74609 | 59.91273
Tønsberg | N/A | Norway | 10.40762 | 59.26754
Bialystok | N/A | Poland | 23.16433 | 53.13333
Chorzów | N/A | Poland | 18.9742 | 50.30582
Lodz | N/A | Poland | 19.47395 | 51.77058
Lodz | N/A | Poland | 19.47395 | 51.77058
Lublin | N/A | Poland | 22.56667 | 51.25
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wroclaw | N/A | Poland | 17.03333 | 51.1
Amadora | N/A | Portugal | -9.23083 | 38.75382
Porto | N/A | Portugal | -8.61099 | 41.14961
Tomar | N/A | Portugal | -8.40924 | 39.60199
Viana do Castelo | N/A | Portugal | -8.83287 | 41.69323
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Lasi | N/A | Romania | N/A | N/A
Oradea | N/A | Romania | 21.91833 | 47.0458
Timișoara | N/A | Romania | 21.22571 | 45.75372
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Martin | N/A | Slovakia | 18.92399 | 49.06651
Poprad | N/A | Slovakia | 20.29798 | 49.06144
Skalica | N/A | Slovakia | 17.22635 | 48.8449
Trenčín | N/A | Slovakia | 18.04436 | 48.89452
Žilina | N/A | Slovakia | 18.73941 | 49.22315
Bloemfontein | N/A | South Africa | 26.214 | -29.12107
Hatfield | N/A | South Africa | 28.24314 | -25.74973
Lyttelton | N/A | South Africa | 28.2012 | -25.82988
Paarl | N/A | South Africa | 18.97523 | -33.73378
Pietermaritzburg | N/A | South Africa | 30.39278 | -29.61679
Barcelona | N/A | Spain | 2.15899 | 41.38879
Bilbao | N/A | Spain | -2.92528 | 43.26271
Esplugues de Llobregat-Barcelo | N/A | Spain | N/A | N/A
Fuenlabrada | N/A | Spain | -3.79415 | 40.28419
Getafe | N/A | Spain | -3.73295 | 40.30571
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Mataró | N/A | Spain | 2.4445 | 41.54211
Miranda de Ebro | N/A | Spain | -2.94695 | 42.6865
Palma de Mallorca | N/A | Spain | 2.65024 | 39.56939
Seville | N/A | Spain | -5.97317 | 37.38283
Toledo | N/A | Spain | -4.02263 | 39.8581
Valencia | N/A | Spain | -0.37966 | 39.47391
Villarreal de Huerva | N/A | Spain | -1.28983 | 41.19034
Borås | N/A | Sweden | 12.9401 | 57.72101
Helsingborg | N/A | Sweden | 12.69437 | 56.04673
Örebro | N/A | Sweden | 15.2066 | 59.27412
Skövde | N/A | Sweden | 13.84506 | 58.39118
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Umeå | N/A | Sweden | 20.25972 | 63.82842
Uppsala | N/A | Sweden | 17.63889 | 59.85882
Frauenfeld | N/A | Switzerland | 8.89893 | 47.55776
Lucerne | N/A | Switzerland | 8.30635 | 47.05048
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Birmingham | N/A | United Kingdom | -1.89983 | 52.48142
Chorley | N/A | United Kingdom | -2.61667 | 53.65
Croydon | N/A | United Kingdom | -0.1 | 51.38333
Liverpool | N/A | United Kingdom | -2.97794 | 53.41058
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
Newcastle upon Tyne | N/A | United Kingdom | -1.61396 | 54.97328
Northwood | N/A | United Kingdom | -0.42454 | 51.61162
Reading | N/A | United Kingdom | -0.97113 | 51.45625
Reading | N/A | United Kingdom | -0.97113 | 51.45625
Sheffield | N/A | United Kingdom | -1.4659 | 53.38297
Swansea | N/A | United Kingdom | -3.94323 | 51.62079 | 1,978 | 0 | 0 | 0 | NCT00689104 | 1COMPLETED | 2009-03-24 | 2008-04-28 | Astellas Pharma Inc | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 1,935 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | The purpose of the study is to assess the safety and efficacy of telcagepant (MK-0974) in acute treatment of multiple migraine attacks with or without aura. Primary hypotheses of this study are that telcagepant is superior to placebo, as measured by the proportion of participants who have pain freedom, pain relief, pain freedom consistency, pain relief consistency, and absence of photophobia, phonophobia, and nausea at 2 hours post-dose. | null | Migraines | multiple attacks of moderate to severe migraine headaches | null | 4 | arm 1: Telcagepant 140 mg, oral, tablet, across 4 migraine attacks. For migraine attack 1 only, if no headache relief is obtained after 2 hours post dose, or if the migraine recurs after 2 hours of the initial treatment, participants may receive an optional second dose of telcagepant 140 mg or placebo. arm 2: Telcagepant 280 mg, oral, tablet, across 4 migraine attacks. For migraine attack 1 only, if no headache relief is obtained after 2 hours post dose, or if the migraine recurs after 2 hours of the initial treatment, participants may receive an optional second dose of telcagepant 280 mg or placebo. arm 3: Placebo, oral, tablet, across 3 migraine attacks (1st, 2nd, and 4th). Telcagepant 140 mg will be administered for the 3rd migraine attack. Participants will receive placebo for the optional second dose. For migraine attacks 2, 3, and 4, no study medication will be provided as an optional second dose. arm 4: Placebo, oral, tablet, across 3 migraine attacks (1st, 2nd, and 3rd). Telcagepant 140 mg will be administered for the 4th migraine attack. Participants will receive placebo for the optional second dose. For migraine attacks 2, 3, and 4, no study medication will be provided as an optional second dose. | [
0,
0,
2,
2
] | 3 | [
0,
0,
0
] | intervention 1: Telcagepant 140 mg tablets intervention 2: Telcagepant 280 mg tablets intervention 3: Placebo tablets | intervention 1: Telcagepant 140 mg intervention 2: Talcagepant 280 mg intervention 3: Placebo | 0 | null | 1,677 | 0 | 0 | 0 | NCT00483704 | 1COMPLETED | 2009-03-25 | 2008-08-14 | Merck Sharp & Dohme LLC | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 102 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | To evaluate safety information of BW430C when administered using the lower starting doses and slower dose escalations as recommended Global Data Sheet | null | Epilepsy | epilepsy Incidence of rash safety evaluation for initial dose patients with Valproic acid | null | 1 | arm 1: None | [
0
] | 1 | [
0
] | intervention 1: anti-epileptic drug | intervention 1: lamictal | 2 | Kumamoto | N/A | Japan | 130.69181 | 32.80589
N/A | N/A | N/A | N/A | N/A | 204 | 0 | 0 | 0 | NCT00395694 | 1COMPLETED | 2009-03-26 | 2006-08-07 | GlaxoSmithKline | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2,
3
] | 7 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 1SINGLE | false | 2MALE | true | Duchenne muscular dystrophy (DMD), a fatal muscle degenerative disorder, arises from mutations in the dystrophin gene. Antisense therapy with the use of antisense oligonucleotides (AON) has the potential to restore effectively the production of dystrophin, the defective protein, in \>70% of DMD. This could result in increased life expectancy through improved muscle survival and function. Recent scientific research has demonstrated the potential of this technique to skip mutated dystrophin exons, restore the reading frame and generate functional dystrophin protein. Having demonstrated proof-of-principle in human cell culture and animal model studies, we now intend to determine efficacy and safety of this approach to induce dystrophin exon skipping in children with DMD.
The specific aim of this phase I/II study is to assess efficacy (dystrophin production) and safety of intramuscular administered morpholino oligomer directed against exon 51 (AVI-4658 PMO). We are performing parallel preclinical studies to develop methods of systemic delivery that will be necessary for future phase II/III clinical studies. | Duchenne Muscular Dystrophy (DMD) is the most common form of muscular dystrophy affecting 1 in every 3500 live male births. The disease is characterised by severe muscle wasting and weakness, which becomes clinically evident between the ages of 3 to 5 years. Affected individuals stop walking by 12 years of age and usually do not survive beyond the age of 20 unless ventilated. In general DMD is caused by mutations that disrupt the reading frame thus leading to a failure to express dystrophin.
Recent scientific research has led to the belief that DMD may be treated by correcting the genetic error in the dystrophin gene which causes DMD. Most children with DMD have a deletion, i.e., a mutation which removes part of the dystrophin gene. A novel technique using antisense technology to skip a specific exon and bypass faulty genetic material, thus allowing production of functional dystrophin to be produced, has been developed.These antisense oligonucleotides (AON) target and bypass faulty genetic material and allow production of functional protein.This has been successfully demonstrated in cultured human DMD cells and in mouse and canine DMD models.The restored production of dystrophin is predicted to reduce muscle pathology significantly.
In the early part of the study we compared different antisense oligomers chemical modification and concluded that the morpholino backbone is significantly superior when administered to skeletal muscle compared to a number of other types of antisense.
The aim of this phase I/II clinical study is to assess efficacy and safety of AVI-4658, a morpholino antisense directed against exon 51, in DMD individuals with deletions which would benefit from skipping exon 51.
The proposed work is presented in 4 sections detailing the main approaches.
Study design
This dose escalation IM trial will involve of up to 9 subjects, subdivided in three groups, of three subjects each. Patients in group 1 will be recruited sequentially whilst patients in groups 2 and 3 will be recruited serially.
* Group 1 (3 patients) will receive intramuscular administration of a low concentration of study drug (extensor digitorum brevis muscle, EDB) and will undergo a muscle biopsy between days 14 and 28 after intramuscular (IM) administration of the AVI-4658.
* Group 2 (3 patients) will undergo an identical procedure but receiving an intermediate dose of the AVI-4658.
* Group 3 (3 patients) will be recruited to receive the highest dose of the AVI-4658 but only if the results in the first 2 cohort of patients show a lack of efficacy of the lower doses. Up to an additional 3 subjects may be enrolled in cohorts 1 or 2, should cohort 3 not be enrolled.
Screening
* A physical examination, including body weight, height, arm span, neuromuscular examination and vital signs (blood pressure, pulse, respiration, and temperature).
* Neuropsychiatric assessment of both subject and the family.
* Molecular genetic on blood sample and dystrophin analysis of original muscle biopsy obtained at diagnosis.
* Muscle MRI scans of lower limbs to assess the preservation of the muscle to be targeted with the injection of AON.
* Biochemical (blood) and urine investigation to include standard biochemistry and haematology (full blood count; coagulation screen; liver function test; serum Ig; protein electrophoresis; inflammatory markers; creatinine kinase; gamma glutamyl transferase; urine biochemistry).
* Cardiovascular assessments: ECG and heart echocardiogram.
* Pulmonary assessments: Forced vital capacity, overnight oxygen saturation monitoring.
* Skin biopsy for MyoD-transfection.
Procedure
* The muscle to be used is the extensor digitorum brevis, a foot muscle with very little function in children with mobility difficulties.
* Local injection will be performed directly through the skin using a combined EMG-delivery needle. While the procedure could be performed under local anaesthetic; where possible, it will be performed under general anaesthetic in order to reduce distress to the subject. A skin tattoo featuring a 1 cm x 1 cm grid with 2 lines in between to divide it in 9 smaller squares will be used to mark the site of the injection precisely and for a subsequent muscle biopsy.
* The total volume of each injection will be 100 μL containing the AVI-4658. Nine injections will be performed at 3 mm intervals inside the 1 cm2 grid tattoo. The depth of the injection will be carefully recorded.
Observation
* Patients will be closely monitored within the clinical research facility by designated nursing staff educated in the trial protocol and with experience in similar Phase I/II studies.
* The clinical research facility has close access to intensive care unit facilities in the event of an unforeseen adverse reaction.
Follow-up Day 2 - Patients will be discharged. Prior to discharge, a brief physical examination and systems review will be performed.
Day 3 - A further brief physical examination and systems review including examination of the injection sites and reporting of any reactions. This examination can be performed at the local surgery or at the hospital of the referring clinician.
Days 5, 7 - Contact with the subject and inquire as to current status.
Day 14 to 28 - The subject is admitted to hospital. Perform systems assessment (physical examination), body weight and vital signs. Blood and urine biochemistry will be repeated then as well as open biopsies of both injected muscles will be performed under general or local anaesthetic.
Day 30 - Contact with the subject and inquiry as to current status.
Day 60 - Contact the subject and inquiry as to current status.
Day 120 - (Final Visit at the hospital where the study drug was administered). A brief physical examination and systems review will be performed.
MDEX Consortium.
The PRECLINICAL studies were performed by the following groups, who are all members of the MDEX consortium:
1. Prof Francesco Muntoni, Dr. Jennifer Morgan. Dubowitz Neuromuscular Centre, Department of Paediatrics, Imperial College Hammersmith Hospital Campus, Du Cane Road London W12 ONN
2. Prof Dominic Wells; Dr Kim Wells. Gene Targeting Group, Department of Cellular and Molecular Neuroscience Division of Neuroscience and Mental Health, Imperial College, Charing Cross Campus, St. Dunstan's Road, London W6 8RP
3. Prof George Dickson; Dr Ian Graham. Gene Therapy Laboratory, Centre for Biomedical Sciences, Royal Holloway - University of London, Egham
4. Dr Matthew Wood. Department of Physiology, Anatomy and Genetics, South Parks Road,Oxford OX1 3QX, United Kingdom (UK).
5. Professor Steve Wilton. Experimental Molecular Medicine Group, Centre for Neuromuscular and Neurological Disorders, University of Western Australia
Additional CLINICAL SUPPORT other than the Study officials will be provided by:
Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Hospital Campus, Du Cane Road, W12ONN: Prof Caroline Sewry; Dr. Maria Kinali; Dr Virginia Arechavala; Dr Lucy Feng
Department of Surgery, St Mary's Hospital Trust, Imperial College Praed Street, London, W2 1NY: Mr David Hunt
DNA Laboratory, Genetics Centre, 5th Floor Guy's Tower, Guy's Hospital London SE1 9RT: Dr Steve Abbs
Academic Unit of Child and Adolescent Psychiatry, Division of Neuroscience and Mental Health, Imperial College, St Mary's Campus, Norfolk Place, Paddington,London, W2 1PG: Professor Elena Garralda
MDEX Study coordinator:
Dr K Ganeshaguru, Dubowitz Neuromuscular Centre, Department of Paediatrics, Hammersmith Hospital Campus, Imperial College London, Du Cane Road, W12ONN, k.ganeshaguru@imperial.ac.uk | Duchenne Muscular Dystrophy | Duchenne muscular dystrophy; antisense oligonucleotides; gene restoration; deletion | null | 2 | arm 1: Low dose of AVI-4658 arm 2: High dose of AVI-4658 | [
0,
0
] | 1 | [
0
] | intervention 1: morpholino antisense oligonucleotide | intervention 1: AVI-4658 (PMO) | 1 | London | N/A | United Kingdom | -0.12574 | 51.50853 | 7 | 0 | 0 | 0 | NCT00159250 | 1COMPLETED | 2009-03-31 | 2007-10-26 | Imperial College London | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
2
] | 3 | RANDOMIZED | CROSSOVER | 9OTHER | 1SINGLE | true | 0ALL | false | The purpose of this study is to compare subjective drug liking using the Drug Rating Questionnaire, subject version (DRQ-S), question 2 and pharmacokinetics of Vyvanse™ and ADDERALL XR® when administered as an oral solution.
Hypothesis: DRQ-S, question 2 will show no difference between the two drugs | Not required | Healthy | Not required | null | 2 | arm 1: 50mg capsule that has been emptied and made into solution arm 2: 20mg capsule that has been emptied, crushed, and made into solution | [
0,
0
] | 2 | [
0,
0
] | intervention 1: Study is a two-period cross-over design where subjects will have 2 Screening visits, a Baseline visit, and then be enrolled into the study for 2 Periods. Each Period has 2-3 visits and lasts from 2-6 weeks. At each Period visit subjects will be given one of the two treatment arm drugs that have been solubilized and then have blood drawn for pharmacokinetic analysis and the Drug Rating Questionnaire administered. At the end of Period 1 subjects will be crossed-over to the alternative treatment drug for the Period 2. The Vyvanse™ capsule contents will emptied into water to make a solution and given to subjects to drink at the beginning of each Period visit. intervention 2: Same visits as described for Vyvanse™. The ADDERALL XR® capsule contents will be crushed, solubilized with water, and given to subjects to drink prior to pharmacokinetic blood draws and DRQ-S administration over the course of two periods. | intervention 1: Lisdexamfetamine Dimesylate intervention 2: Racemic mixture of dextroamphetamine and lisdexamfetamine | 1 | Boston | Massachusetts | United States | -71.05977 | 42.35843 | 3 | 0 | 0 | 0 | NCT00776555 | 6TERMINATED | 2009-03-31 | 2008-11-21 | Shire | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 8,231 | RANDOMIZED | PARALLEL | 1PREVENTION | 4QUADRUPLE | false | 2MALE | null | This 4-year study will compare how safe and effective an oral investigational medicine is (compared to placebo) in preventing the development of prostate cancer in men that are defined by the study entrance criteria as being at an increased risk for prostate cancer. Study visits to the clinic will occur every 6 months for up to 4 years (10 clinic visits), and a prostate biopsy will be performed at 2 and 4 years of treatment. | null | Neoplasms, Prostate | Prostate cancer prevention prostate BPH enlarged prostate PSA prostate cancer | null | 2 | arm 1: Eligible subjects will complete a 4-week placebo run-in followed by randomization to matched placebo in a 1:1 ratio. arm 2: Eligible subjects will complete a 4-week placebo run-in followed by randomization to 0.5mg dutasteride in a 1:1 ratio. Randomization will be stratified by center. | [
2,
0
] | 2 | [
0,
0
] | intervention 1: After successful completion of the placebo run-in phase, subjects who continue to meet eligibility requirements will be randomized into the double-blind phase of the study and issued a 6-month supply of study drug. Subjects will self-administer study drug once daily dosing of 0.5mg of dutasteride orally for up to 4 years. intervention 2: After successful completion of the placebo run-in phase, subjects who continue to meet eligibility requirements will be randomized into the double-blind phase of the study and issued a 6-month supply of study drug. Subjects will self-administer study drug once daily orally for up to 4 years. | intervention 1: Dutasteride intervention 2: Placebo | 932 | Birmingham | Alabama | United States | -86.80249 | 33.52066
Homewood | Alabama | United States | -86.80082 | 33.47177
Huntsville | Alabama | United States | -86.58594 | 34.7304
Mobile | Alabama | United States | -88.04305 | 30.69436
Anchorage | Alaska | United States | -149.90028 | 61.21806
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix | Arizona | United States | -112.07404 | 33.44838
Scottsdale | Arizona | United States | -111.89903 | 33.50921
Sun City | Arizona | United States | -112.27182 | 33.59754
Tucson | Arizona | United States | -110.92648 | 32.22174
Tucson | Arizona | United States | -110.92648 | 32.22174
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Anaheim | California | United States | -117.9145 | 33.83529
Atherton | California | United States | -122.19774 | 37.46133
Culver City | California | United States | -118.39647 | 34.02112
Encino | California | United States | -118.50119 | 34.15917
Fountain Valley | California | United States | -117.95367 | 33.70918
Fresno | California | United States | -119.77237 | 36.74773
Irvine | California | United States | -117.82311 | 33.66946
La Mesa | California | United States | -117.02308 | 32.76783
Laguna Hills | California | United States | -117.71283 | 33.61252
Long Beach | California | United States | -118.18923 | 33.76696
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Mather | California | United States | -119.85573 | 37.88215
Newport Beach | California | United States | -117.92895 | 33.61891
Orange | California | United States | -117.85311 | 33.78779
Pico Rivera | California | United States | -118.09673 | 33.98307
Poway | California | United States | -117.03586 | 32.96282
Sacramento | California | United States | -121.4944 | 38.58157
Salinas | California | United States | -121.6555 | 36.67774
San Bernardino | California | United States | -117.28977 | 34.10834
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Francisco | California | United States | -122.41942 | 37.77493
San Francisco | California | United States | -122.41942 | 37.77493
San Ramon | California | United States | -121.97802 | 37.77993
Santa Monica | California | United States | -118.49138 | 34.01949
Stanford | California | United States | -122.16608 | 37.42411
Temecula | California | United States | -117.14836 | 33.49364
Torrance | California | United States | -118.34063 | 33.83585
Upland | California | United States | -117.64839 | 34.09751
Van Nuys | California | United States | -118.44897 | 34.18667
Walnut Creek | California | United States | -122.06496 | 37.90631
Westchester | California | United States | -118.40063 | 33.95973
Aurora | Colorado | United States | -104.83192 | 39.72943
Aurora | Colorado | United States | -104.83192 | 39.72943
Denver | Colorado | United States | -104.9847 | 39.73915
Denver | Colorado | United States | -104.9847 | 39.73915
Englewood | Colorado | United States | -104.98776 | 39.64777
Longmont | Colorado | United States | -105.10193 | 40.16721
Hartford | Connecticut | United States | -72.68509 | 41.76371
Middlebury | Connecticut | United States | -73.12761 | 41.52787
New Britain | Connecticut | United States | -72.77954 | 41.66121
Trumbull | Connecticut | United States | -73.20067 | 41.24287
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Aventura | Florida | United States | -80.13921 | 25.95648
Clearwater | Florida | United States | -82.8001 | 27.96585
Clearwater | Florida | United States | -82.8001 | 27.96585
Delray Beach | Florida | United States | -80.07282 | 26.46146
Fort Myers | Florida | United States | -81.84059 | 26.62168
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Lake Worth | Florida | United States | -80.07231 | 26.61708
Largo | Florida | United States | -82.78842 | 27.90979
Longwood | Florida | United States | -81.3384 | 28.70305
Margate | Florida | United States | -80.20644 | 26.24453
Melbourne | Florida | United States | -80.60811 | 28.08363
Miami | Florida | United States | -80.19366 | 25.77427
New Port Richey | Florida | United States | -82.71927 | 28.24418
Ocala | Florida | United States | -82.14009 | 29.1872
Ocala | Florida | United States | -82.14009 | 29.1872
Okeechobee | Florida | United States | -80.82978 | 27.24393
Orange Park | Florida | United States | -81.70648 | 30.16607
Orlando | Florida | United States | -81.37924 | 28.53834
Panama City | Florida | United States | -85.65983 | 30.15946
Plantation | Florida | United States | -80.23184 | 26.13421
Sarasota | Florida | United States | -82.53065 | 27.33643
South Daytona | Florida | United States | -81.0045 | 29.16582
St. Petersburg | Florida | United States | -82.67927 | 27.77086
Stuart | Florida | United States | -80.25283 | 27.19755
Tallahassee | Florida | United States | -84.28073 | 30.43826
Tamarac | Florida | United States | -80.24977 | 26.21286
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Atlanta | Georgia | United States | -84.38798 | 33.749
Atlanta | Georgia | United States | -84.38798 | 33.749
Atlanta | Georgia | United States | -84.38798 | 33.749
Augusta | Georgia | United States | -81.97484 | 33.47097
Fayetteville | Georgia | United States | -84.45493 | 33.44873
Marietta | Georgia | United States | -84.54993 | 33.9526
Roswell | Georgia | United States | -84.36159 | 34.02316
Woodstock | Georgia | United States | -84.51938 | 34.10149
Honolulu | Hawaii | United States | -157.85833 | 21.30694
Coeur d'Alene | Idaho | United States | -116.78047 | 47.67768
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Galesburg | Illinois | United States | -90.37124 | 40.94782
Kankakee | Illinois | United States | -87.86115 | 41.12003
Maywood | Illinois | United States | -87.84312 | 41.8792
Melrose Park | Illinois | United States | -87.85673 | 41.90059
Niles | Illinois | United States | -87.80284 | 42.01892
Springfield | Illinois | United States | -89.64371 | 39.80172
Evansville | Indiana | United States | -87.55585 | 37.97476
Fort Wayne | Indiana | United States | -85.12886 | 41.1306
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Jeffersonville | Indiana | United States | -85.73718 | 38.27757
Kansas City | Kansas | United States | -94.62746 | 39.11417
Overland Park | Kansas | United States | -94.67079 | 38.98223
Wichita | Kansas | United States | -97.33754 | 37.69224
Lexington | Kentucky | United States | -84.47772 | 37.98869
Covington | Louisiana | United States | -90.10042 | 30.47549
Gretna | Louisiana | United States | -90.05396 | 29.91465
Houma | Louisiana | United States | -90.71953 | 29.59577
Lafayette | Louisiana | United States | -92.01984 | 30.22409
Metairie | Louisiana | United States | -90.15285 | 29.98409
New Orleans | Louisiana | United States | -90.07507 | 29.95465
New Orleans | Louisiana | United States | -90.07507 | 29.95465
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Ruston | Louisiana | United States | -92.63793 | 32.52321
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Annapolis | Maryland | United States | -76.49184 | 38.97859
Baltimore | Maryland | United States | -76.61219 | 39.29038
Greenbelt | Maryland | United States | -76.87553 | 39.00455
Owings Mills | Maryland | United States | -76.78025 | 39.41955
Rockville | Maryland | United States | -77.15276 | 39.084
Towson | Maryland | United States | -76.60191 | 39.4015
Boston | Massachusetts | United States | -71.05977 | 42.35843
Braintree | Massachusetts | United States | -71.00215 | 42.20384
Haverhill | Massachusetts | United States | -71.07728 | 42.7762
Milford | Massachusetts | United States | -71.51617 | 42.13982
Newton | Massachusetts | United States | -71.20922 | 42.33704
Springfield | Massachusetts | United States | -72.58981 | 42.10148
Waltham | Massachusetts | United States | -71.23561 | 42.37649
Watertown | Massachusetts | United States | -71.18283 | 42.37093
West Yarmouth | Massachusetts | United States | -70.24113 | 41.65011
Wocester | Massachusetts | United States | N/A | N/A
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
Detroit | Michigan | United States | -83.04575 | 42.33143
Royal Oak | Michigan | United States | -83.14465 | 42.48948
Saint Joseph | Michigan | United States | -86.48002 | 42.10976
Chaska | Minnesota | United States | -93.60218 | 44.78941
Edina | Minnesota | United States | -93.34995 | 44.88969
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Rochester | Minnesota | United States | -92.4699 | 44.02163
Saint Cloud | Minnesota | United States | -94.16249 | 45.5608
Hattiesburg | Mississippi | United States | -89.29034 | 31.32712
Jackson | Mississippi | United States | -90.18481 | 32.29876
Kansas City | Missouri | United States | -94.57857 | 39.09973
Springfield | Missouri | United States | -93.29824 | 37.21533
St Louis | Missouri | United States | -90.19789 | 38.62727
St Louis | Missouri | United States | -90.19789 | 38.62727
St Louis | Missouri | United States | -90.19789 | 38.62727
Billings | Montana | United States | -108.50069 | 45.78329
Omaha | Nebraska | United States | -95.94043 | 41.25626
Omaha | Nebraska | United States | -95.94043 | 41.25626
Henderson | Nevada | United States | -114.98194 | 36.0397
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Reno | Nevada | United States | -119.8138 | 39.52963
Reno | Nevada | United States | -119.8138 | 39.52963
Lebanon | New Hampshire | United States | -72.25176 | 43.64229
Edison | New Jersey | United States | -74.4121 | 40.51872
Hackensack | New Jersey | United States | -74.04347 | 40.88593
Lawrencevill | New Jersey | United States | N/A | N/A
Marlton | New Jersey | United States | -74.92183 | 39.89122
Perth Amboy | New Jersey | United States | -74.26542 | 40.50677
Voorhees Township | New Jersey | United States | -74.49062 | 40.4795
West Orange | New Jersey | United States | -74.23904 | 40.79871
Albany | New York | United States | -73.75623 | 42.65258
Binghamton | New York | United States | -75.91797 | 42.09869
Brooklyn | New York | United States | -73.94958 | 40.6501
East Syracuse | New York | United States | -76.07853 | 43.06534
Elmont | New York | United States | -73.71291 | 40.70094
Endwell | New York | United States | -76.02103 | 42.11285
Garden City | New York | United States | -73.6343 | 40.72677
Great Neck | New York | United States | -73.72846 | 40.80066
Mineola | New York | United States | -73.64068 | 40.74927
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Orchard Park | New York | United States | -78.74392 | 42.76756
Poughkeepsie | New York | United States | -73.92097 | 41.70037
Rochester | New York | United States | -77.61556 | 43.15478
Staten Island | New York | United States | -74.13986 | 40.56233
Syracuse | New York | United States | -76.14742 | 43.04812
The Bronx | New York | United States | -73.86641 | 40.84985
Cary | North Carolina | United States | -78.78112 | 35.79154
Cary | North Carolina | United States | -78.78112 | 35.79154
Chapel Hill | North Carolina | United States | -79.05584 | 35.9132
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Charlotte, NC 28207 | North Carolina | United States | -80.84313 | 35.22709
Concord | North Carolina | United States | -80.58158 | 35.40888
Durham | North Carolina | United States | -78.89862 | 35.99403
Greensboro | North Carolina | United States | -79.79198 | 36.07264
Greenville | North Carolina | United States | -77.36635 | 35.61266
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Raleigh | North Carolina | United States | -78.63861 | 35.7721
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Bismarck | North Dakota | United States | -100.78374 | 46.80833
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Columbus | Ohio | United States | -82.99879 | 39.96118
Columbus | Ohio | United States | -82.99879 | 39.96118
Columbus | Ohio | United States | -82.99879 | 39.96118
Elyria | Ohio | United States | -82.10765 | 41.36838
Kettering | Ohio | United States | -84.16883 | 39.6895
Marion | Ohio | United States | -83.12852 | 40.58867
Zanesville | Ohio | United States | -82.01319 | 39.94035
Oklahoma City | Oklahoma | United States | -97.51643 | 35.46756
Poca City | Oklahoma | United States | N/A | N/A
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Oregon City | Oregon | United States | -122.60676 | 45.35734
Portland | Oregon | United States | -122.67621 | 45.52345
Portland | Oregon | United States | -122.67621 | 45.52345
Portland | Oregon | United States | -122.67621 | 45.52345
Springfield | Oregon | United States | -123.02203 | 44.04624
Bala-Cynwyd | Pennsylvania | United States | -75.23407 | 40.00761
Bryn Mawr | Pennsylvania | United States | -80.08672 | 40.30396
Camp Hill | Pennsylvania | United States | -76.91997 | 40.23981
Harrisburg | Pennsylvania | United States | -76.88442 | 40.2737
Hershey | Pennsylvania | United States | -76.65025 | 40.28592
Lancaster | Pennsylvania | United States | -76.30551 | 40.03788
Lancaster | Pennsylvania | United States | -76.30551 | 40.03788
Monroeville | Pennsylvania | United States | -79.7881 | 40.42118
Newton | Pennsylvania | United States | -75.8952 | 41.22258
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Rosemont | Pennsylvania | United States | -75.3238 | 40.02567
Sellersville | Pennsylvania | United States | -75.3049 | 40.35399
State College | Pennsylvania | United States | -77.86 | 40.79339
Cranston | Rhode Island | United States | -71.43728 | 41.77982
Providence | Rhode Island | United States | -71.41283 | 41.82399
West Warwick | Rhode Island | United States | -71.52194 | 41.69689
Charleston | South Carolina | United States | -79.93275 | 32.77632
Greenville | South Carolina | United States | -82.39401 | 34.85262
Greer | South Carolina | United States | -82.22706 | 34.93873
Myrtle Beach | South Carolina | United States | -78.88669 | 33.68906
Simpsonville | South Carolina | United States | -82.25428 | 34.73706
Fort Pierre | South Dakota | United States | -100.37374 | 44.35359
Germantown | Tennessee | United States | -89.81009 | 35.08676
Knoxville | Tennessee | United States | -83.92074 | 35.96064
Memphis | Tennessee | United States | -90.04898 | 35.14953
Nashville | Tennessee | United States | -86.78444 | 36.16589
Nashville | Tennessee | United States | -86.78444 | 36.16589
Amarillo | Texas | United States | -101.8313 | 35.222
Arlington | Texas | United States | -97.10807 | 32.73569
Austin | Texas | United States | -97.74306 | 30.26715
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Fort Worth | Texas | United States | -97.32085 | 32.72541
Fort Worth | Texas | United States | -97.32085 | 32.72541
Houston | Texas | United States | -95.36327 | 29.76328
Houston | Texas | United States | -95.36327 | 29.76328
San Antonio | Texas | United States | -98.49363 | 29.42412
Texarkana | Texas | United States | -94.04769 | 33.42513
Salt Lake City | Utah | United States | -111.89105 | 40.76078
South Burlington | Vermont | United States | -73.17096 | 44.46699
Alexandria | Virginia | United States | -77.04692 | 38.80484
Charlottesville | Virginia | United States | -78.47668 | 38.02931
Fairfax | Virginia | United States | -77.30637 | 38.84622
Harrisonburg | Virginia | United States | -78.86892 | 38.44957
Mechanicsville | Virginia | United States | -77.37331 | 37.60876
Norfolk | Virginia | United States | -76.28522 | 36.84681
Richmond | Virginia | United States | -77.46026 | 37.55376
Salem | Virginia | United States | -80.05476 | 37.29347
Virginia Beach | Virginia | United States | -75.97799 | 36.85293
Graham | Washington | United States | -122.29428 | 47.05288
Seattle | Washington | United States | -122.33207 | 47.60621
Seattle | Washington | United States | -122.33207 | 47.60621
Seattle | Washington | United States | -122.33207 | 47.60621
Seattle | Washington | United States | -122.33207 | 47.60621
Seattle | Washington | United States | -122.33207 | 47.60621
Spokane | Washington | United States | -117.42908 | 47.65966
Tacoma | Washington | United States | -122.44429 | 47.25288
Tacoma | Washington | United States | -122.44429 | 47.25288
Tacoma | Washington | United States | -122.44429 | 47.25288
Madison | Wisconsin | United States | -89.40123 | 43.07305
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Cheyenne | Wyoming | United States | -104.82025 | 41.13998
Av Córdoba 2424 | Buenos Aires | Argentina | N/A | N/A
Bahía Blanca | Buenos Aires | Argentina | -62.26545 | -38.7176
Capital Federal | Buenos Aires | Argentina | N/A | N/A
Capital Federal | Buenos Aires | Argentina | N/A | N/A
Ciudad Autonoma de Buenos Aires | Buenos Aires | Argentina | N/A | N/A
Córdoba | Córdoba Province | Argentina | -64.18853 | -31.40648
Córdoba | Córdoba Province | Argentina | -64.18853 | -31.40648
Rosario | Santa Fe Province | Argentina | -60.63932 | -32.94682
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Darlinghurst | New South Wales | Australia | 151.21925 | -33.87939
Kogarah | New South Wales | Australia | 151.13564 | -33.9681
Randwick | New South Wales | Australia | 151.24895 | -33.91439
Westmead | New South Wales | Australia | 150.98768 | -33.80383
Herston | Queensland | Australia | 153.01852 | -27.44453
Kippa-Ring | Queensland | Australia | 153.0835 | -27.22586
Woolloongabba | Queensland | Australia | 153.03655 | -27.48855
Adelaide | South Australia | Australia | 138.59863 | -34.92866
Mentone | Victoria | Australia | 145.06667 | -37.98333
Parkville | Victoria | Australia | 144.95 | -37.78333
Innsbruck | N/A | Austria | 11.39454 | 47.26266
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Minsk | N/A | Belarus | 27.56653 | 53.90019
Minsk | N/A | Belarus | 27.56653 | 53.90019
Aalst | N/A | Belgium | 4.0355 | 50.93604
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Ghent | N/A | Belgium | 3.71667 | 51.05
Hasselt | N/A | Belgium | 5.33781 | 50.93106
Kortrijk | N/A | Belgium | 3.26487 | 50.82803
Leuven | N/A | Belgium | 4.70093 | 50.87959
Mons | N/A | Belgium | 3.95229 | 50.45413
Turnhout | N/A | Belgium | 4.94471 | 51.32254
Wilrijk | N/A | Belgium | 4.39513 | 51.16734
Yvoir | N/A | Belgium | 4.88059 | 50.3279
Salvador | Estado de Bahia | Brazil | -38.49096 | -12.97563
Belo Horizonte | Minas Gerais | Brazil | -43.93778 | -19.92083
Rio de Janeiro | Rio de Janeiro | Brazil | -43.18223 | -22.90642
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
Ribeirão Preto | São Paulo | Brazil | -47.81028 | -21.1775
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Varna | N/A | Bulgaria | 27.91667 | 43.21667
Calgary | Alberta | Canada | -114.08529 | 51.05011
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Kelowna | British Columbia | Canada | -119.48568 | 49.88307
Surrey | British Columbia | Canada | -122.82509 | 49.10635
Vancouver | British Columbia | Canada | -123.11934 | 49.24966
Victoria | British Columbia | Canada | -123.35155 | 48.4359
Victoria | British Columbia | Canada | -123.35155 | 48.4359
Fredericton | New Brunswick | Canada | -66.66558 | 45.94541
Miramichi | New Brunswick | Canada | -65.50186 | 47.02895
Saint John | New Brunswick | Canada | -66.05616 | 45.27076
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Barrie | Ontario | Canada | -79.66634 | 44.40011
Burlington | Ontario | Canada | -79.83713 | 43.38621
Burlington | Ontario | Canada | -79.83713 | 43.38621
Kingston | Ontario | Canada | -76.48098 | 44.22976
Kitchener | Ontario | Canada | -80.5112 | 43.42537
Markham | Ontario | Canada | -79.2663 | 43.86682
Newmarket | Ontario | Canada | -79.46631 | 44.05011
Niagara Falls | Ontario | Canada | -79.06627 | 43.10012
North Bay | Ontario | Canada | -79.46633 | 46.3168
North York | Ontario | Canada | N/A | N/A
Oakville | Ontario | Canada | -79.68292 | 43.45011
Orillia | Ontario | Canada | -79.42068 | 44.60868
Richmond Hill | Ontario | Canada | -79.43725 | 43.87111
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Chicoutimi | Quebec | Canada | -71.06369 | 48.41963
Granby | Quebec | Canada | -72.73243 | 45.40008
Greenfield Park | Quebec | Canada | -73.46223 | 45.48649
Laval | Quebec | Canada | -73.692 | 45.56995
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Pointe-Claire | Quebec | Canada | -73.81669 | 45.44868
Québec | Quebec | Canada | -71.21454 | 46.81228
Trois-Rivières | Quebec | Canada | -72.5477 | 46.34515
Viña del Mar | Región de Valparaíso | Chile | -71.55183 | -33.02457
Santiago | Región Metro de Santiago | Chile | -70.64827 | -33.45694
Zagreb | N/A | Croatia | 15.97798 | 45.81444
Herlev | N/A | Denmark | 12.43998 | 55.72366
Middelfart | N/A | Denmark | 9.73054 | 55.50591
Nakskov | N/A | Denmark | 11.13567 | 54.83038
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Helsinki | N/A | Finland | 24.93545 | 60.16952
Helsinki | N/A | Finland | 24.93545 | 60.16952
Kuopio | N/A | Finland | 27.67703 | 62.89238
Lahti | N/A | Finland | 25.66151 | 60.98267
Lappeenranta | N/A | Finland | 28.18871 | 61.05871
Oulu | N/A | Finland | 25.46816 | 65.01236
Oulu | N/A | Finland | 25.46816 | 65.01236
Rovaniemi | N/A | Finland | 25.71667 | 66.5
Seinäjoki | N/A | Finland | 22.82822 | 62.79446
Tampere | N/A | Finland | 23.78712 | 61.49911
Turku | N/A | Finland | 22.26869 | 60.45148
Amiens | N/A | France | 2.3 | 49.9
Arcachon | N/A | France | -1.17255 | 44.66126
Auch | N/A | France | 0.58856 | 43.64561
Besançon | N/A | France | 6.01815 | 47.24878
Bois-Bernard | N/A | France | 2.91149 | 50.38147
Bordeaux | N/A | France | -0.5805 | 44.84044
Boujan-sur-Libron | N/A | France | 3.24749 | 43.37082
Cabestany | N/A | France | 2.9409 | 42.68141
Caen | N/A | France | -0.35912 | 49.18585
Cannes | N/A | France | 7.01275 | 43.55135
Carpentras | N/A | France | 5.04813 | 44.05507
Chalon-sur-Saône | N/A | France | 4.85372 | 46.78112
Châlons-en-Champagne | N/A | France | 4.36724 | 48.95393
Cholet | N/A | France | -0.87974 | 47.05893
Créteil | N/A | France | 2.46569 | 48.79266
Dijon | N/A | France | 5.01667 | 47.31667
Domarin | N/A | France | 5.24599 | 45.58662
Dunkirk | N/A | France | 2.37681 | 51.0344
Fourmies | N/A | France | 4.04784 | 50.01532
Grande-Synthe | N/A | France | 2.29975 | 51.0154
Guilherand-Granges | N/A | France | 4.87372 | 44.93278
Le Havre | N/A | France | 0.10785 | 49.49346
Le Raincy | N/A | France | 2.52298 | 48.89916
Lille | N/A | France | 3.05858 | 50.63297
Longjumeau | N/A | France | 2.29431 | 48.69307
Lyon | N/A | France | 4.84671 | 45.74846
Marseille | N/A | France | 5.38107 | 43.29695
Marseille | N/A | France | 5.38107 | 43.29695
Montauban | N/A | France | 1.3542 | 44.01759
Montpellier | N/A | France | 3.87635 | 43.61093
Nîmes | N/A | France | 4.35788 | 43.83665
Orléans | N/A | France | 1.90389 | 47.90289
Orsay | N/A | France | 2.18727 | 48.69572
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Pau | N/A | France | -0.35583 | 43.31117
Pierre-Bénite | N/A | France | 4.82424 | 45.70359
Ploemeur | N/A | France | -3.42952 | 47.73512
Poitiers | N/A | France | 0.34348 | 46.58261
Reims | N/A | France | 4.02853 | 49.26526
Rouen | N/A | France | 1.09932 | 49.44313
Saint-Cyr-sur-Loire | N/A | France | 0.66667 | 47.4
Saint-Etienne | N/A | France | 4.39 | 45.43389
Saint-Etienne | N/A | France | 4.39 | 45.43389
Saint-Grégoire | N/A | France | -1.68579 | 48.15101
Saint-Martin-d'Hères | N/A | France | 5.76281 | 45.1787
Saint-Nazaire | N/A | France | -2.2179 | 47.27506
Saint-Quentin | N/A | France | 3.28757 | 49.84889
Suresnes | N/A | France | 2.22929 | 48.87143
Toulouse | N/A | France | 1.44367 | 43.60426
Tours | N/A | France | 0.70398 | 47.39484
Tours | N/A | France | 0.70398 | 47.39484
Troyes | N/A | France | 4.08524 | 48.30073
Vannes | N/A | France | -2.76205 | 47.65688
Backnang | Baden-Wurttemberg | Germany | 9.43718 | 48.94743
Bad Schönborn | Baden-Wurttemberg | Germany | 8.64179 | 49.20122
Bruchsal | Baden-Wurttemberg | Germany | 8.59804 | 49.12426
Esslingen am Neckar | Baden-Wurttemberg | Germany | 9.30473 | 48.73961
Freiburg im Breisgau | Baden-Wurttemberg | Germany | 7.85222 | 47.9959
Kleinblittersdorf | Baden-Wurttemberg | Germany | N/A | N/A
Mannheim | Baden-Wurttemberg | Germany | 8.46694 | 49.4891
Neckargemünd | Baden-Wurttemberg | Germany | 8.7959 | 49.38899
Ostfildern | Baden-Wurttemberg | Germany | 9.24954 | 48.72704
Rheinfelden | Baden-Wurttemberg | Germany | 7.78715 | 47.56013
Waldkirch | Baden-Wurttemberg | Germany | 7.96371 | 48.09585
Aichach | Bavaria | Germany | 11.13413 | 48.45755
Augsburg | Bavaria | Germany | 10.89851 | 48.37154
Bad Griesbach | Bavaria | Germany | 13.19329 | 48.45181
Bamberg | Bavaria | Germany | 10.90067 | 49.89873
Dachau | Bavaria | Germany | 11.43402 | 48.26
Ebersberg | Bavaria | Germany | 11.97063 | 48.0771
Forchheim | Bavaria | Germany | 11.05877 | 49.71754
Fürth | Bavaria | Germany | 10.98856 | 49.47593
Garmisch-Partenkirchen | Bavaria | Germany | 11.09576 | 47.49209
Günzburg | Bavaria | Germany | 10.27695 | 48.45599
Herzogenaurach | Bavaria | Germany | 10.88565 | 49.56798
Höchberg | Bavaria | Germany | 9.88223 | 49.78446
Kelheim | Bavaria | Germany | 11.88618 | 48.91725
Koenigsbrunn | Bavaria | Germany | N/A | N/A
Munich | Bavaria | Germany | 11.57549 | 48.13743
Munich | Bavaria | Germany | 11.57549 | 48.13743
Munich | Bavaria | Germany | 11.57549 | 48.13743
Neumarkt in der Oberpfalz | Bavaria | Germany | 11.46278 | 49.28028
Nuremberg | Bavaria | Germany | 11.07752 | 49.45421
Nuremberg | Bavaria | Germany | 11.07752 | 49.45421
Nuremberg | Bavaria | Germany | 11.07752 | 49.45421
Nuremberg | Bavaria | Germany | 11.07752 | 49.45421
Planegg | Bavaria | Germany | 11.42483 | 48.10672
Rosenheim | Bavaria | Germany | 12.12247 | 47.85637
Roth | Bavaria | Germany | 11.09111 | 49.24762
Starnberg | Bavaria | Germany | 11.34416 | 48.00193
Starnberg | Bavaria | Germany | 11.34416 | 48.00193
Weiden | Bavaria | Germany | 12.15613 | 49.67682
Weißenburg in Bayern | Bavaria | Germany | 10.97221 | 49.03095
Wertheim | Bavaria | Germany | N/A | N/A
Hagenow | Brandenburg | Germany | N/A | N/A
Hennigsdorf | Brandenburg | Germany | 13.20419 | 52.63598
Oranienburg | Brandenburg | Germany | 13.24197 | 52.75577
Schwedt | Brandenburg | Germany | 14.28154 | 53.05963
Senftenberg | Brandenburg | Germany | 14.00164 | 51.52517
Strausberg | Brandenburg | Germany | 13.88741 | 52.57859
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Wedel | City state of Hamburg | Germany | N/A | N/A
Bad Homburg | Hesse | Germany | 8.61816 | 50.22683
Frankfurt am Main | Hesse | Germany | 8.68417 | 50.11552
Frankfurt am Main | Hesse | Germany | 8.68417 | 50.11552
Frankfurt am Main | Hesse | Germany | 8.68417 | 50.11552
Frankfurt am Main | Hesse | Germany | 8.68417 | 50.11552
Hochheim am Main | Hesse | Germany | 8.35218 | 50.01436
Kelkheim | Hesse | Germany | 8.4502 | 50.13703
Marburg | Hesse | Germany | 8.77069 | 50.80904
Neustadt | Hesse | Germany | 9.03417 | 49.81778
Offenbach | Hesse | Germany | 8.76647 | 50.10061
Seligenstadt | Hesse | Germany | 8.97394 | 50.0432
Vellmar | Hesse | Germany | 9.47974 | 51.35806
Wiesbaden | Hesse | Germany | 8.24932 | 50.08258
Braunschweig | Lower Saxony | Germany | 10.52673 | 52.26594
Braunschweig | Lower Saxony | Germany | 10.52673 | 52.26594
Bremervörde | Lower Saxony | Germany | 9.14306 | 53.48458
Buchholz | Lower Saxony | Germany | 9.56287 | 53.00884
Buxtehude | Lower Saxony | Germany | 9.68636 | 53.46716
Ganderkesee | Lower Saxony | Germany | 8.53333 | 53.03333
Göttingen | Lower Saxony | Germany | 9.93228 | 51.53443
Hildesheim | Lower Saxony | Germany | 9.95112 | 52.15077
Holzminden | Lower Saxony | Germany | 9.4455 | 51.82798
Leer | Lower Saxony | Germany | 7.461 | 53.23157
Salzgitter | Lower Saxony | Germany | 10.4154 | 52.15705
Wolfsburg | Lower Saxony | Germany | 10.7815 | 52.42452
Bad Doberan | Mecklenburg-Vorpommern | Germany | 11.90051 | 54.10712
Ludwigslust | Mecklenburg-Vorpommern | Germany | 11.49714 | 53.32917
Ribnitz-Damgarten | Mecklenburg-Vorpommern | Germany | 12.45666 | 54.2422
Rostock | Mecklenburg-Vorpommern | Germany | 12.14049 | 54.0887
Rostock | Mecklenburg-Vorpommern | Germany | 12.14049 | 54.0887
Schwerin | Mecklenburg-Vorpommern | Germany | 11.41316 | 53.62937
Schwerin | Mecklenburg-Vorpommern | Germany | 11.41316 | 53.62937
Wismar | Mecklenburg-Vorpommern | Germany | 11.45563 | 53.89218
Aachen | North Rhine-Westphalia | Germany | 6.08342 | 50.77664
Arnsberg | North Rhine-Westphalia | Germany | 8.08333 | 51.38333
Bocholt | North Rhine-Westphalia | Germany | 6.61531 | 51.83879
Bonn | North Rhine-Westphalia | Germany | 7.09549 | 50.73438
Borken | North Rhine-Westphalia | Germany | 6.85774 | 51.84382
Cologne | North Rhine-Westphalia | Germany | 6.95 | 50.93333
Dortmund | North Rhine-Westphalia | Germany | 7.466 | 51.51494
Duisburg | North Rhine-Westphalia | Germany | 6.76516 | 51.43247
Duisburg | North Rhine-Westphalia | Germany | 6.76516 | 51.43247
Duisburg | North Rhine-Westphalia | Germany | 6.76516 | 51.43247
Dülmen | North Rhine-Westphalia | Germany | 7.28075 | 51.83149
Düsseldorf | North Rhine-Westphalia | Germany | 6.77616 | 51.22172
Düsseldorf | North Rhine-Westphalia | Germany | 6.77616 | 51.22172
Düsseldorf | North Rhine-Westphalia | Germany | 6.77616 | 51.22172
Erkrath | North Rhine-Westphalia | Germany | 6.90831 | 51.22235
Essen | North Rhine-Westphalia | Germany | 7.01228 | 51.45657
Essen | North Rhine-Westphalia | Germany | 7.01228 | 51.45657
Gelsenkirchen | North Rhine-Westphalia | Germany | 7.09654 | 51.50508
Gelsenkirchen | North Rhine-Westphalia | Germany | 7.09654 | 51.50508
Kamp-Lintfort | North Rhine-Westphalia | Germany | 6.54587 | 51.50467
Kempen | North Rhine-Westphalia | Germany | 6.41858 | 51.36432
Königswinter | North Rhine-Westphalia | Germany | 7.19245 | 50.67734
Krefeld | North Rhine-Westphalia | Germany | 6.55381 | 51.33645
Krefeld | North Rhine-Westphalia | Germany | 6.55381 | 51.33645
Langenfeld | North Rhine-Westphalia | Germany | 6.94831 | 51.10821
Marl | North Rhine-Westphalia | Germany | 7.09038 | 51.65671
Moers | North Rhine-Westphalia | Germany | 6.6326 | 51.45342
Mülheim | North Rhine-Westphalia | Germany | 6.87967 | 51.43218
Oberhausen | North Rhine-Westphalia | Germany | 6.8625 | 51.47805
Paderborn | North Rhine-Westphalia | Germany | 8.75439 | 51.71905
Pulheim | North Rhine-Westphalia | Germany | 6.80632 | 50.99965
Wesseling | North Rhine-Westphalia | Germany | 6.9747 | 50.82709
Wuppertal | North Rhine-Westphalia | Germany | 7.14816 | 51.25627
Bad Bergzaben | Rhineland-Palatinate | Germany | 8.00092 | 49.10245
Bad Ems | Rhineland-Palatinate | Germany | 7.71369 | 50.33544
Dierdorf | Rhineland-Palatinate | Germany | 7.65271 | 50.54647
Koblenz | Rhineland-Palatinate | Germany | 7.57883 | 50.35357
Nieder-Olm | Rhineland-Palatinate | Germany | 8.20533 | 49.91166
Homburg | Saarland | Germany | 7.33867 | 49.32637
Bad Schlema | Saxony | Germany | 12.67288 | 50.60257
Bautzen | Saxony | Germany | 14.43494 | 51.18035
Chemnitz | Saxony | Germany | 12.92922 | 50.8357
Chemnitz | Saxony | Germany | 12.92922 | 50.8357
Döbeln | Saxony | Germany | 13.11027 | 51.1221
Dresden | Saxony | Germany | 13.73832 | 51.05089
Dresden | Saxony | Germany | 13.73832 | 51.05089
Grimma | Saxony | Germany | 12.71959 | 51.23367
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Markkleeberg | Saxony | Germany | 12.36906 | 51.2755
Neustadt | Saxony | Germany | 14.71344 | 51.53213
Oelsnitz | Saxony | Germany | 12.1695 | 50.4147
Pirna | Saxony | Germany | 13.93702 | 50.95843
Plauen | Saxony | Germany | 12.13782 | 50.4973
Radebeul | Saxony | Germany | 13.66047 | 51.10654
Schwarzenberg | Saxony | Germany | 12.78522 | 50.53791
Wilkau-Haßlau | Saxony | Germany | 12.51482 | 50.67504
Zwickau | Saxony | Germany | 12.48839 | 50.72724
Dessau | Saxony-Anhalt | Germany | 12.24555 | 51.83864
Dessau | Saxony-Anhalt | Germany | 12.24555 | 51.83864
Eisleben Lutherstadt | Saxony-Anhalt | Germany | 11.54835 | 51.52754
Gardelegen | Saxony-Anhalt | Germany | 11.39523 | 52.5252
Halle | Saxony-Anhalt | Germany | 11.97947 | 51.48158
Hettstedt | Saxony-Anhalt | Germany | 11.51146 | 51.6503
Leuna | Saxony-Anhalt | Germany | 12.01589 | 51.31783
Magdeburg | Saxony-Anhalt | Germany | 11.62916 | 52.12773
Naumburg | Saxony-Anhalt | Germany | 11.80979 | 51.14987
Weißenfels | Saxony-Anhalt | Germany | 11.96843 | 51.20148
Wolmirstedt | Saxony-Anhalt | Germany | 11.62945 | 52.24856
Ahrensburg | Schleswig-Holstein | Germany | 10.22593 | 53.67515
Bad Schwartau | Schleswig-Holstein | Germany | 10.69691 | 53.91887
Flensburg | Schleswig-Holstein | Germany | 9.43722 | 54.78805
Hemmoor | Schleswig-Holstein | Germany | N/A | N/A
Husum | Schleswig-Holstein | Germany | 9.05239 | 54.4858
Itzehoe | Schleswig-Holstein | Germany | 9.51529 | 53.92099
Kiel | Schleswig-Holstein | Germany | 10.13489 | 54.32133
Lauenburg | Schleswig-Holstein | Germany | 10.55654 | 53.37199
Lübeck | Schleswig-Holstein | Germany | 10.68729 | 53.86893
Lübeck | Schleswig-Holstein | Germany | 10.68729 | 53.86893
Neumünster | Schleswig-Holstein | Germany | 9.98456 | 54.07399
Plön | Schleswig-Holstein | Germany | 10.42765 | 54.16202
Schleswig | Schleswig-Holstein | Germany | 9.56829 | 54.52021
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Gera | Thuringia | Germany | 12.08187 | 50.88029
Gotha | Thuringia | Germany | 10.70193 | 50.94823
Ilmenau | Thuringia | Germany | 10.91858 | 50.68322
Meiningen | Thuringia | Germany | 10.41521 | 50.56787
Waltershausen | Thuringia | Germany | 10.55791 | 50.89827
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Heraklion, Crete | N/A | Greece | 25.14341 | 35.32787
Ioannina | N/A | Greece | 20.85189 | 39.66486
Larissa | N/A | Greece | 22.41761 | 39.63689
Periohi Dragana, Alexandroupolis | N/A | Greece | 25.87644 | 40.84995
Rhodes | N/A | Greece | 28.22199 | 36.43556
Rio, Patras | N/A | Greece | N/A | N/A
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Győr | N/A | Hungary | 17.63512 | 47.68333
Kecskemét | N/A | Hungary | 19.69128 | 46.90618
Miskolc | N/A | Hungary | 20.77806 | 48.10306
Cork | N/A | Ireland | -8.47061 | 51.89797
Dublin | N/A | Ireland | -6.24889 | 53.33306
Tallaght | N/A | Ireland | -6.37344 | 53.2859
Lanciano (CH) | Abruzzo | Italy | 14.39024 | 42.22718
Bari | Apulia | Italy | 16.86982 | 41.12066
Caserta | Campania | Italy | 14.33231 | 41.07262
Napoli | Campania | Italy | 14.5195 | 40.87618
Forlì | Emilia-Romagna | Italy | 12.04144 | 44.22177
Rome | Lazio | Italy | 12.51133 | 41.89193
Milan | Lombardy | Italy | 9.18951 | 45.46427
Milan | Lombardy | Italy | 9.18951 | 45.46427
Voghera (PV) | Lombardy | Italy | 9.01175 | 44.99151
Cagliari | Sardinia | Italy | 9.11917 | 39.23054
Sassari | Sardinia | Italy | 8.55552 | 40.72586
Catania | Sicily | Italy | 15.07041 | 37.49223
Ragusa (CT) | Sicily | Italy | 14.72443 | 36.92574
Pisa | Tuscany | Italy | 10.4036 | 43.70853
Isola Della Scala (VR) | Veneto | Italy | 11.00824 | 45.26943
Napoli | Veneto | Italy | N/A | N/A
Chiba | N/A | Japan | 140.11667 | 35.6
Fukuoka | N/A | Japan | 130.41667 | 33.6
Hokkaido | N/A | Japan | N/A | N/A
Ibaraki | N/A | Japan | 135.56828 | 34.81641
Nagasaki | N/A | Japan | 129.88333 | 32.75
Ōita | N/A | Japan | 131.6 | 33.23333
Daugavpils | N/A | Latvia | 26.53333 | 55.88333
Riga | N/A | Latvia | 24.10589 | 56.946
Riga | N/A | Latvia | 24.10589 | 56.946
Riga | N/A | Latvia | 24.10589 | 56.946
Riga | N/A | Latvia | 24.10589 | 56.946
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Šiauliai | N/A | Lithuania | 23.31667 | 55.93333
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Durango | Durango | Mexico | -104.65756 | 24.02032
Durango | Durango | Mexico | -104.65756 | 24.02032
Zapopan | Jalisco | Mexico | -103.38742 | 20.72111
Zapopan | Jalisco | Mexico | -103.38742 | 20.72111
Zapopan, Jalisco | Jalisco | Mexico | N/A | N/A
Mexico | N/A | Mexico | -98.43784 | 18.88011
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
México | N/A | Mexico | -103.57339 | 22.76088
Puebla City | N/A | Mexico | -98.20723 | 19.04778
's-Hertogenbosch | N/A | Netherlands | 5.30417 | 51.69917
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Arnhem | N/A | Netherlands | 5.91111 | 51.98
Breda | N/A | Netherlands | 4.77596 | 51.58656
Capelle aan den IJssel | N/A | Netherlands | 4.57778 | 51.92917
Ede | N/A | Netherlands | 5.65833 | 52.03333
Eindhoven | N/A | Netherlands | 5.47778 | 51.44083
Harderwijk | N/A | Netherlands | 5.62083 | 52.34167
Hengelo | N/A | Netherlands | 6.79306 | 52.26583
Nieuwegein | N/A | Netherlands | 5.08056 | 52.02917
Nijmegen | N/A | Netherlands | 5.85278 | 51.8425
Nijmegen | N/A | Netherlands | 5.85278 | 51.8425
Roermond | N/A | Netherlands | 5.9875 | 51.19417
Roosendaal | N/A | Netherlands | 4.46528 | 51.53083
Rotterdam | N/A | Netherlands | 4.47917 | 51.9225
Rotterdam | N/A | Netherlands | 4.47917 | 51.9225
Stadskanaal | N/A | Netherlands | 6.9504 | 52.98947
The Hague | N/A | Netherlands | 4.29861 | 52.07667
The Hague | N/A | Netherlands | 4.29861 | 52.07667
Tilburg | N/A | Netherlands | 5.0913 | 51.55551
Auckland | N/A | New Zealand | 174.76349 | -36.84853
Christchurch | N/A | New Zealand | 172.63333 | -43.53333
Hamilton | N/A | New Zealand | 175.28333 | -37.78333
Nelson | N/A | New Zealand | 173.28404 | -41.27078
Tauranga | N/A | New Zealand | 176.16667 | -37.68611
Whangarei | N/A | New Zealand | 174.32391 | -35.73167
Arendal | N/A | Norway | 8.77253 | 58.46151
Moelv | N/A | Norway | 10.7 | 60.93333
Oslo | N/A | Norway | 10.74609 | 59.91273
Porsgrunn | N/A | Norway | 9.6561 | 59.14054
Stavanger | N/A | Norway | 5.73332 | 58.97005
Bydgoszcz | N/A | Poland | 18.00762 | 53.1235
Bydgoszcz | N/A | Poland | 18.00762 | 53.1235
Chęciny | N/A | Poland | 20.46229 | 50.80021
Elblag | N/A | Poland | 19.40884 | 54.1522
Gdansk | N/A | Poland | 18.64912 | 54.35227
Inowrocław | N/A | Poland | 18.26387 | 52.79886
Katowice | N/A | Poland | 19.02754 | 50.25841
Kościerzyna | N/A | Poland | 17.98119 | 54.12226
Krakow | N/A | Poland | 19.93658 | 50.06143
Lublin | N/A | Poland | 22.56667 | 51.25
Rzeszów | N/A | Poland | 21.99901 | 50.04132
Szczecin | N/A | Poland | 14.55302 | 53.42894
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wejherowo | N/A | Poland | 18.23559 | 54.60568
Wroclaw | N/A | Poland | 17.03333 | 51.1
Almada | N/A | Portugal | -9.1569 | 38.67902
Amadora | N/A | Portugal | -9.23083 | 38.75382
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Porto | N/A | Portugal | -8.61099 | 41.14961
Porto | N/A | Portugal | -8.61099 | 41.14961
Ponce | Puerto Rico | Puerto Rico | -66.62398 | 18.01031
San Juan | Puerto Rico | Puerto Rico | -66.10572 | 18.46633
San Juan | Puerto Rico | Puerto Rico | -66.10572 | 18.46633
Bucharest | N/A | Romania | 26.10626 | 44.43225
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Nizhny Novgorod | N/A | Russia | 44.00205 | 56.32867
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saratov | N/A | Russia | 46.00861 | 51.54056
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Martin | N/A | Slovakia | 18.92399 | 49.06651
Celje | N/A | Slovenia | 15.26044 | 46.23092
Ljubljana | N/A | Slovenia | 14.50513 | 46.05108
Maribor | N/A | Slovenia | 15.64667 | 46.55472
Slovenj Gradec | N/A | Slovenia | 15.08056 | 46.51028
Rosebank | Gauteng | South Africa | 28.03589 | -26.14563
Cape Town | N/A | South Africa | 18.42322 | -33.92584
Cape Town | N/A | South Africa | 18.42322 | -33.92584
Capital Park | N/A | South Africa | 28.18884 | -25.72514
George | N/A | South Africa | 22.46173 | -33.963
Johannesburg | N/A | South Africa | 28.04363 | -26.20227
Parktown | N/A | South Africa | 28.02671 | -26.18205
Pretoria | N/A | South Africa | 28.18783 | -25.74486
Westville, Durban | N/A | South Africa | N/A | N/A
Alava | N/A | Spain | -6.19946 | 43.36057
Alcala de Henares (Madrid) | N/A | Spain | -3.35996 | 40.48205
Alcorcón | N/A | Spain | -3.82487 | 40.34582
Badalona | N/A | Spain | 2.24741 | 41.45004
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Bilbao | N/A | Spain | -2.92528 | 43.26271
Castellon | N/A | Spain | -0.04935 | 39.98567
Ciudad Real | N/A | Spain | -3.92907 | 38.98626
Don Benito (Badajoz) | N/A | Spain | -5.86162 | 38.95627
Donostia / San Sebastian | N/A | Spain | -1.97499 | 43.31283
Galdakano | N/A | Spain | N/A | N/A
Granada | N/A | Spain | -3.60667 | 37.18817
Ibiza Town | N/A | Spain | 1.43296 | 38.90883
Jaén | N/A | Spain | -3.79028 | 37.76922
La Laguna (Santa Cruz de Tenerife) | N/A | Spain | -16.32014 | 28.4853
Leganés | N/A | Spain | -3.7635 | 40.32718
Logroño | N/A | Spain | -2.45 | 42.46667
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Manacor | N/A | Spain | 3.20955 | 39.56964
Málaga | N/A | Spain | -4.42034 | 36.72016
Orihuela | N/A | Spain | -0.94401 | 38.08483
Oviedo | N/A | Spain | -5.84476 | 43.36029
Pamplona | N/A | Spain | -1.64323 | 42.81687
Sagunto | N/A | Spain | -0.26667 | 39.68333
Sant Joan d'Alacant | N/A | Spain | -0.43623 | 38.40148
Santa Cruz de Tenerife | N/A | Spain | -16.25462 | 28.46824
Seville | N/A | Spain | -5.97317 | 37.38283
Seville | N/A | Spain | -5.97317 | 37.38283
Seville | N/A | Spain | -5.97317 | 37.38283
Seville | N/A | Spain | -5.97317 | 37.38283
Soria | N/A | Spain | -2.46883 | 41.76401
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Valladolid | N/A | Spain | -4.72372 | 41.65518
Via-Real (Castellón) | N/A | Spain | N/A | N/A
Borås | N/A | Sweden | 12.9401 | 57.72101
Eskilstuna | N/A | Sweden | 16.5077 | 59.36661
Gävle | N/A | Sweden | 17.14174 | 60.67452
Gothenburg | N/A | Sweden | 11.96679 | 57.70716
Gothenburg | N/A | Sweden | 11.96679 | 57.70716
Karlshamn | N/A | Sweden | 14.86188 | 56.1706
Kristianstad | N/A | Sweden | 14.15242 | 56.03129
Kristianstad | N/A | Sweden | 14.15242 | 56.03129
Malmo | N/A | Sweden | 13.00073 | 55.60587
Östersund | N/A | Sweden | 14.63566 | 63.1792
Skärholmen | N/A | Sweden | 17.90196 | 59.27549
Skövde | N/A | Sweden | 13.84506 | 58.39118
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Umeå | N/A | Sweden | 20.25972 | 63.82842
Vålberg | N/A | Sweden | 13.18633 | 59.39145
Aarau | N/A | Switzerland | 8.04422 | 47.39254
Bern | N/A | Switzerland | 7.44744 | 46.94809
Biel | N/A | Switzerland | 8.21773 | 46.45587
Fribourg | N/A | Switzerland | 7.15128 | 46.80237
Geneva | N/A | Switzerland | 6.14569 | 46.20222
Lausanne | N/A | Switzerland | 6.63282 | 46.516
Olten | N/A | Switzerland | 7.90329 | 47.34999
Sarnen | N/A | Switzerland | 8.24531 | 46.89611
Zollikon | N/A | Switzerland | 8.57407 | 47.34019
Sfax | N/A | Tunisia | 10.76028 | 34.74056
Sousse | N/A | Tunisia | 10.63699 | 35.82539
Tunis | N/A | Tunisia | 10.16579 | 36.81897
Tunis | N/A | Tunisia | 10.16579 | 36.81897
Tunis | N/A | Tunisia | 10.16579 | 36.81897
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Capa/Istanbul | N/A | Turkey (Türkiye) | N/A | N/A
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Izmir | N/A | Turkey (Türkiye) | 27.13838 | 38.41273
Dnipro | N/A | Ukraine | 35.04066 | 48.46664
Kharkiv | N/A | Ukraine | 36.25475 | 49.98177
Odesa | N/A | Ukraine | 30.74383 | 46.48572
Zaporizhzhya | N/A | Ukraine | 35.11714 | 47.85167
Aberdeen | Aberdeenshire | United Kingdom | -2.09814 | 57.14369
Ayr | Ayrshire | United Kingdom | -4.63393 | 55.46273
Reading | Berkshire | United Kingdom | -0.97113 | 51.45625
Stockport | Cheshire | United Kingdom | -2.15761 | 53.40979
Exeter | Devon | United Kingdom | -3.52751 | 50.7236
Plymouth | Devon | United Kingdom | -4.14305 | 50.37153
Cardiff | Glamorgan | United Kingdom | -3.18 | 51.48
Bristol | Gloucestershire | United Kingdom | -2.59665 | 51.45523
Portsmouth | Hampshire | United Kingdom | -1.09125 | 50.79899
Southampton | Hampshire | United Kingdom | -1.40428 | 50.90395
Stevenage | Hertfordshire | United Kingdom | -0.20256 | 51.90224
Glasgow | Lanarkshire | United Kingdom | -4.25763 | 55.86515
Buckshaw Village, Chorley | Lancashire | United Kingdom | -2.61667 | 53.65
Lancs | Lancashire | United Kingdom | N/A | N/A
Manchester | Lancashire | United Kingdom | -2.23743 | 53.48095
Manchester | Lancashire | United Kingdom | -2.23743 | 53.48095
Oldham | Lancashire | United Kingdom | -2.1183 | 53.54051
Leicester | Leicestershire | United Kingdom | -1.13169 | 52.6386
Leytonstone | London | United Kingdom | 0.00768 | 51.56856
Liverpool | Merseyside | United Kingdom | -2.97794 | 53.41058
Liverpool | Merseyside | United Kingdom | -2.97794 | 53.41058
Edinburgh | Midlothian | United Kingdom | -3.19648 | 55.95206
Norwich | Norfolk | United Kingdom | 1.29834 | 52.62783
Newcastle upon Tyne | Northumberland | United Kingdom | -1.61396 | 54.97328
Nottingham | Nottinghamshire | United Kingdom | -1.15047 | 52.9536
Bath | Somerset | United Kingdom | -2.36172 | 51.3751
Tauton | Somerset | United Kingdom | N/A | N/A
Stoke-on-Trent | Staffordshire | United Kingdom | -2.18538 | 53.00415
Redhill | Surrey | United Kingdom | -0.17044 | 51.24048
Chichester | Sussex West | United Kingdom | -0.78003 | 50.83673
Birmingham | Warwickshire | United Kingdom | -1.89983 | 52.48142
Coventry | Warwickshire | United Kingdom | -1.51217 | 52.40656
Bradford | N/A | United Kingdom | -1.75206 | 53.79391
Bristol | N/A | United Kingdom | -2.59665 | 51.45523
Clydebank, Glasgow | N/A | United Kingdom | N/A | N/A
Crewe | N/A | United Kingdom | -2.44161 | 53.09787
Edgbaston, Birmingham | N/A | United Kingdom | N/A | N/A
Falkirk | N/A | United Kingdom | -3.78535 | 56.0021
Leeds | N/A | United Kingdom | -1.54785 | 53.79648
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
Sheffield | N/A | United Kingdom | -1.4659 | 53.38297
Torquay | N/A | United Kingdom | -3.52522 | 50.46198
Wakefield | N/A | United Kingdom | -1.49768 | 53.68331
Waterloo, Liverpool | N/A | United Kingdom | N/A | N/A
Wolverhampton | N/A | United Kingdom | -2.12296 | 52.58547
N/A | N/A | N/A | N/A | N/A | 8,231 | 3 | 0.000364 | 1 | NCT00056407 | 1COMPLETED | 2009-04-01 | 2003-03-01 | GlaxoSmithKline | 4INDUSTRY | false | false | false | null | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000124 |
[
4
] | 2,035 | RANDOMIZED | FACTORIAL | 0TREATMENT | 2DOUBLE | false | 0ALL | null | This 4 arm study assessed the efficacy and safety of oral capecitabine (Xeloda) or intravenous (iv) fluorouracil/leucovorin, in combination with iv oxaliplatin (Eloxatin) with or without iv bevacizumab (Avastin), as a first-line treatment in patients with metastatic colorectal cancer. Patients were randomized to receive 1) XELOX (Xeloda 1000 mg/m\^2 orally \[po\] twice a day \[bid\] on Days 1-15 + oxaliplatin in 3 week cycles), 2) FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil \[5-FU\] in 2 week cycles), 3) XELOX + bevacizumab (7.5 mg iv on Day 1 in 3 week cycles), or 4) FOLFOX-4 + bevacizumab (5 mg iv on Day 1 in 2 week cycles). | This study was conducted in 2 parts: An initial 2-arm part in which patients were randomized to 1 of 2 different treatment groups (XELOX or FOLFOX-4), and a subsequent 2 x 2 factorial part, added to the study through a protocol amendment, in which additional patients were randomized into one of 4 different treatment groups (XELOX + placebo, FOLFOX-4 + placebo, XELOX + bevacizumab, or FOLFOX-4 + bevacizumab). Due to the comparison of the oral agent capecitabine with bolus and infused fluorouracil, the study was not blinded with respect to these 2 treatments. The study was double-blind with regard to the administration of bevacizumab, ie, there was a placebo control for bevacizumab in the second part of the study.
The study consisted of 3 phases, a Primary Study Treatment Phase, a Post-Study Treatment Phase, and a Follow-Up Phase.
Primary Study Treatment Phase
Patients were to receive up to 16 cycles (2-arm part of the study) or 24 cycles (4-arm part of the study) of treatment during the Primary Study Treatment Phase (48 weeks).
Post-Study Treatment Phase
Patients who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Patients who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the patient withdrew consent.
Follow-up Phase
Patients who terminated study treatment during the primary or post-study treatment phase were followed until disease progression or death. | Colorectal Cancer | null | 4 | arm 1: Patients in the 2-arm part of the study received oxaliplatin 130 mg/m\^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m\^2 orally twice a day for the first 2 weeks of every 3 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle. arm 2: Patients in the 4-arm part of the study received oxaliplatin 130 mg/m\^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m\^2 orally twice a day for the first 2 weeks of every 3 week cycle + bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle. arm 3: Patients in the 2-arm part of the study received oxaliplatin 85 mg/m\^2 intravenously (iv) + leucovorin 200 mg/m\^2 iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m\^2 bolus injection over 2 to 4 min followed by 600 mg/m\^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle. arm 4: Patients in the 4-arm part of the study received oxaliplatin 85 mg/m\^2 intravenously (iv) + leucovorin 200 mg/m\^2 iv + bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m\^2 bolus injection over 2 to 4 min followed by 600 mg/m\^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle. | [
0,
0,
1,
1
] | 9 | [
0,
0,
0,
0,
0,
0,
0,
0,
0
] | intervention 1: Oxaliplatin was administered in a 2 h infusion before the first dose of capecitabine. intervention 2: Capecitabine was taken within 30 min after the end of breakfast and dinner. intervention 3: Bevacizumab was administered in a 30 to 90 min infusion. intervention 4: Placebo control for bevacizumab (volume equivalent to 7.5 mg/kg bevacizumab) was administered in a 30 to 90 min infusion. intervention 5: Oxaliplatin 85 mg/m\^2 was administered simultaneously with leucovorin in a 2 h infusion. intervention 6: Leucovorin was administered simultaneously with oxaliplatin 85 mg/m\^2 in a 2 h infusion. intervention 7: None intervention 8: Bevacizumab was administered in a 30 to 90 min infusion. intervention 9: Placebo control for bevacizumab (volume equivalent to 5 mg/kg bevacizumab) was administered in a 30 to 90 min infusion. | intervention 1: Oxaliplatin 130 mg/m^2 intervention 2: Capecitabine 1000 mg/m^2 intervention 3: Bevacizumab 7.5 mg/kg intervention 4: Placebo for bevacizumab 7.5 mg/kg intervention 5: Oxaliplatin 85 mg/m^2 intervention 6: Leucovorin 200 mg/m^2 intervention 7: Fluorouracil 400 mg/m^2 intervention 8: Bevacizumab 5 mg/kg intervention 9: Placebo for bevacizumab 5 mg/kg | 236 | Berkeley | California | United States | -122.27275 | 37.87159
Fountain Valley | California | United States | -117.95367 | 33.70918
Fullerton | California | United States | -117.92534 | 33.87029
Gilroy | California | United States | -121.56828 | 37.00578
Greenbrae | California | United States | -122.5247 | 37.94854
Los Angeles | California | United States | -118.24368 | 34.05223
Orange | California | United States | -117.85311 | 33.78779
Palo Alto | California | United States | -122.14302 | 37.44188
San Diego | California | United States | -117.16472 | 32.71571
Norwich | Connecticut | United States | -72.07591 | 41.52426
Waterbury | Connecticut | United States | -73.0515 | 41.55815
Boca Raton | Florida | United States | -80.0831 | 26.35869
Gainesville | Florida | United States | -82.32483 | 29.65163
Jacksonville | Florida | United States | -81.65565 | 30.33218
New Port Richey | Florida | United States | -82.71927 | 28.24418
Tampa | Florida | United States | -82.45843 | 27.94752
Tampa | Florida | United States | -82.45843 | 27.94752
Atlanta | Georgia | United States | -84.38798 | 33.749
Chicago | Illinois | United States | -87.65005 | 41.85003
Elk Grove Village | Illinois | United States | -87.97035 | 42.00392
Peoria | Illinois | United States | -89.58899 | 40.69365
Lexington | Kentucky | United States | -84.47772 | 37.98869
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Scarborough | Maine | United States | -70.32172 | 43.57814
Boston | Massachusetts | United States | -71.05977 | 42.35843
Ann Arbor | Michigan | United States | -83.74088 | 42.27756
Saint Louis Park | Minnesota | United States | -93.34801 | 44.9483
Las Vegas | Nevada | United States | -115.13722 | 36.17497
East Orange | New Jersey | United States | -74.20487 | 40.76732
Hamilton | New Jersey | United States | -74.08125 | 40.20706
New Brunswick | New Jersey | United States | -74.45182 | 40.48622
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Farmington | New Mexico | United States | -108.21869 | 36.72806
New York | New York | United States | -74.00597 | 40.71427
Rochester | New York | United States | -77.61556 | 43.15478
Syracuse | New York | United States | -76.14742 | 43.04812
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Bismarck | North Dakota | United States | -100.78374 | 46.80833
Fargo | North Dakota | United States | -96.7898 | 46.87719
Sayre | Pennsylvania | United States | -76.5155 | 41.97896
Upland | Pennsylvania | United States | -75.38269 | 39.85261
Providence | Rhode Island | United States | -71.41283 | 41.82399
Charleston | South Carolina | United States | -79.93275 | 32.77632
Columbia | South Carolina | United States | -81.03481 | 34.00071
Memphis | Tennessee | United States | -90.04898 | 35.14953
Houston | Texas | United States | -95.36327 | 29.76328
Burlington | Vermont | United States | -73.21207 | 44.47588
Richmond | Virginia | United States | -77.46026 | 37.55376
Adelaide | N/A | Australia | 138.59863 | -34.92866
Box Hill | N/A | Australia | 145.12545 | -37.81887
Brisbane | N/A | Australia | 153.02809 | -27.46794
Camperdown | N/A | Australia | 151.17642 | -33.88965
Fitzroy | N/A | Australia | 144.97833 | -37.79839
Footscray | N/A | Australia | 144.9 | -37.8
Kurralta Park | N/A | Australia | 138.56702 | -34.95142
Malvern | N/A | Australia | 145.02811 | -37.86259
Melbourne | N/A | Australia | 144.96332 | -37.814
Melbourne | N/A | Australia | 144.96332 | -37.814
Perth | N/A | Australia | 115.8614 | -31.95224
Port Macquarie | N/A | Australia | 152.90894 | -31.43084
St Leonards | N/A | Australia | 151.19836 | -33.82344
Sydney | N/A | Australia | 151.20732 | -33.86785
Sydney | N/A | Australia | 151.20732 | -33.86785
Vienna | N/A | Austria | 16.37208 | 48.20849
Wels | N/A | Austria | 14.03333 | 48.16667
Jaú | N/A | Brazil | -48.55778 | -22.29639
Rio de Janeiro | N/A | Brazil | -43.18223 | -22.90642
São Paulo | N/A | Brazil | -46.63611 | -23.5475
Calgary | Alberta | Canada | -114.08529 | 51.05011
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Kelowna | British Columbia | Canada | -119.48568 | 49.88307
North Vancouver | British Columbia | Canada | -123.06934 | 49.31636
Surrey | British Columbia | Canada | -122.82509 | 49.10635
Vancouver | British Columbia | Canada | -123.11934 | 49.24966
Victoria | British Columbia | Canada | -123.35155 | 48.4359
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Hamilton | Ontario | Canada | -79.84963 | 43.25011
London | Ontario | Canada | -81.23304 | 42.98339
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Oshawa | Ontario | Canada | -78.84957 | 43.90012
Ottawa | Ontario | Canada | -75.69812 | 45.41117
St. Catharines | Ontario | Canada | -79.24267 | 43.17126
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Lévis | Quebec | Canada | -71.17793 | 46.80326
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Québec | Quebec | Canada | -71.21454 | 46.81228
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Guangdong | N/A | China | 129.33635 | 42.76832
Guangzhou | N/A | China | 113.25 | 23.11667
Jiangsu | N/A | China | N/A | N/A
Jiangxi | N/A | China | 105.19994 | 33.99934
Shandong | N/A | China | 114.95747 | 26.82656
Shanghai | N/A | China | 121.45806 | 31.22222
Shanghai | N/A | China | 121.45806 | 31.22222
Tianjin | N/A | China | 117.17667 | 39.14222
Wuhan | N/A | China | 114.26667 | 30.58333
Brno | N/A | Czechia | 16.60796 | 49.19522
Chomutov | N/A | Czechia | 13.41779 | 50.46048
Hradec Králové | N/A | Czechia | 15.83277 | 50.20923
Ostrava | N/A | Czechia | 18.28204 | 49.83465
Copenhagen | N/A | Denmark | 12.56553 | 55.67594
Herlev | N/A | Denmark | 12.43998 | 55.72366
Odense | N/A | Denmark | 10.38831 | 55.39594
Helsinki | N/A | Finland | 24.93545 | 60.16952
Tampere | N/A | Finland | 23.78712 | 61.49911
Turku | N/A | Finland | 22.26869 | 60.45148
Besançon | N/A | France | 6.01815 | 47.24878
Bobigny | N/A | France | 2.45012 | 48.90982
Boulogne-Billancourt | N/A | France | 2.24128 | 48.83545
Brest | N/A | France | -4.48628 | 48.39029
Chambray-lès-Tours | N/A | France | 0.70286 | 47.33537
Colmar | N/A | France | 7.35584 | 48.08078
Dijon | N/A | France | 5.01667 | 47.31667
Grenoble | N/A | France | 5.71479 | 45.17869
Lyon | N/A | France | 4.84671 | 45.74846
Metz | N/A | France | 6.17269 | 49.11911
Nice | N/A | France | 7.26608 | 43.70313
Nice | N/A | France | 7.26608 | 43.70313
Nîmes | N/A | France | 4.35788 | 43.83665
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Pierre-Bénite | N/A | France | 4.82424 | 45.70359
Rouen | N/A | France | 1.09932 | 49.44313
Saint-Herblain | N/A | France | -1.651 | 47.21154
Saint-Herblain | N/A | France | -1.651 | 47.21154
Toulouse | N/A | France | 1.44367 | 43.60426
Bochum | N/A | Germany | 7.21648 | 51.48165
Halle | N/A | Germany | 11.97947 | 51.48158
Hanover | N/A | Germany | 9.73322 | 52.37052
Herne | N/A | Germany | 7.22572 | 51.5388
Leipzig | N/A | Germany | 12.37129 | 51.33962
Mainz | N/A | Germany | 8.2791 | 49.98419
Mannheim | N/A | Germany | 8.46694 | 49.4891
Regensburg | N/A | Germany | 12.10161 | 49.01513
Stralsund | N/A | Germany | 13.0818 | 54.30911
Trier | N/A | Germany | 6.63935 | 49.75565
Guatemala City | N/A | Guatemala | -90.51327 | 14.64072
Guatemala City | N/A | Guatemala | -90.51327 | 14.64072
Hong Kong | N/A | Hong Kong | 114.17469 | 22.27832
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Győr | N/A | Hungary | 17.63512 | 47.68333
Kecskemét | N/A | Hungary | 19.69128 | 46.90618
Cork | N/A | Ireland | -8.47061 | 51.89797
Dublin | N/A | Ireland | -6.24889 | 53.33306
Dublin | N/A | Ireland | -6.24889 | 53.33306
Galway | N/A | Ireland | -9.05095 | 53.27245
Haifa | N/A | Israel | 34.99928 | 32.81303
Jerusalem | N/A | Israel | 35.21633 | 31.76904
Petah Tikva | N/A | Israel | 34.88747 | 32.08707
Tel Aviv | N/A | Israel | 34.78057 | 32.08088
Ẕerifin | N/A | Israel | 34.84852 | 31.95731
Ancona | N/A | Italy | 13.5103 | 43.60717
Genova | N/A | Italy | 11.87211 | 45.21604
Modena | N/A | Italy | 10.92539 | 44.64783
Padua | N/A | Italy | 11.88586 | 45.40797
Parma | N/A | Italy | 10.32618 | 44.79935
Pavia | N/A | Italy | 9.15917 | 45.19205
Reggio Emilia | N/A | Italy | 10.63125 | 44.69825
Sassari | N/A | Italy | 8.55552 | 40.72586
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Christchurch | N/A | New Zealand | 172.63333 | -43.53333
Bergen | N/A | Norway | 5.32415 | 60.39299
Oslo | N/A | Norway | 10.74609 | 59.91273
Tromsø | N/A | Norway | 18.95508 | 69.6489
Panama City | N/A | Panama | -79.51973 | 8.9936
Beja | N/A | Portugal | -7.86323 | 38.01506
Lisbon | N/A | Portugal | -9.1498 | 38.72509
San Juan | N/A | Puerto Rico | -66.10572 | 18.46633
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Cape Town | N/A | South Africa | 18.42322 | -33.92584
Pretoria | N/A | South Africa | 28.18783 | -25.74486
Sandton | N/A | South Africa | 28.054 | -26.104
Seoul | N/A | South Korea | 126.9784 | 37.566
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Córdoba | N/A | Spain | -4.77275 | 37.89155
Granada | N/A | Spain | -3.60667 | 37.18817
Leganés | N/A | Spain | -3.7635 | 40.32718
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Málaga | N/A | Spain | -4.42034 | 36.72016
Santander | N/A | Spain | -3.80444 | 43.46472
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Valencia | N/A | Spain | -0.37966 | 39.47391
Zaragoza | N/A | Spain | -0.87734 | 41.65606
Gävle | N/A | Sweden | 17.14174 | 60.67452
Karlstad | N/A | Sweden | 13.50357 | 59.3793
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Uppsala | N/A | Sweden | 17.63889 | 59.85882
Västerås | N/A | Sweden | 16.55276 | 59.61617
Bern | N/A | Switzerland | 7.44744 | 46.94809
Geneva | N/A | Switzerland | 6.14569 | 46.20222
Kueishan | N/A | Taiwan | N/A | N/A
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Khon Kaen | N/A | Thailand | 102.833 | 16.44671
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Izmir | N/A | Turkey (Türkiye) | 27.13838 | 38.41273
Aberdeen | N/A | United Kingdom | -2.09814 | 57.14369
Birmingham | N/A | United Kingdom | -1.89983 | 52.48142
Cardiff | N/A | United Kingdom | -3.18 | 51.48
Derby | N/A | United Kingdom | -1.47663 | 52.92277
Glasgow | N/A | United Kingdom | -4.25763 | 55.86515
Guildford | N/A | United Kingdom | -0.57427 | 51.23536
Hull | N/A | United Kingdom | -0.33525 | 53.7446
London | N/A | United Kingdom | -0.12574 | 51.50853
Maidstone | N/A | United Kingdom | 0.51667 | 51.26667
Newcastle upon Tyne | N/A | United Kingdom | -1.61396 | 54.97328
Northwood | N/A | United Kingdom | -0.42454 | 51.61162
Nottingham | N/A | United Kingdom | -1.15047 | 52.9536
Plymouth | N/A | United Kingdom | -4.14305 | 50.37153
Salisbury | N/A | United Kingdom | -1.79569 | 51.06931
Southampton | N/A | United Kingdom | -1.40428 | 50.90395
Sutton | N/A | United Kingdom | -0.2 | 51.35
Taunton | N/A | United Kingdom | -3.10293 | 51.01494 | 1,998 | 1 | 0.000501 | 0 | NCT00069095 | 1COMPLETED | 2009-04-01 | 2003-07-01 | Hoffmann-La Roche | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000088 | |
[
4
] | 4,844 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 2MALE | null | This study will investigate the efficacy and safety of treatment with dutasteride and tamsulosin, administered once daily for 4 years, alone and in combination, on the improvement of symptoms and clinical outcome in men with moderate to severe symptomatic Benign Prostatic Hyperplasia (BPH). Study visits are every 3 months for up to 4 years (18 clinic visits). Transrectal ultrasound (TRUS) is done annually. | A randomised, double-blind, parallel group study to investigate the efficacy and safety of treatment with Dutasteride (0.5 mg) and Tamsulosin (0.4 mg), administered once daily for 4 years, alone and in combination, on the improvement of symptoms and clinical outcome in men with moderate to severe symptomatic benign prostatic hyperplasia. | Prostatic Hyperplasia | Combination Therapy dutasteride BPH | null | 3 | arm 1: dutasteride 0.5mg once daily arm 2: Combination of dutasteride (0.5mg) and tamsulosin (0.4mg), once daily arm 3: tamsulosin 0.4mg once daily | [
1,
0,
1
] | 2 | [
0,
0
] | intervention 1: combination or single agent intervention 2: combination agent or single agent | intervention 1: dutasteride 0.5mg once daily for 4 years intervention 2: tamsulosin 0.4mg once daily for 4 years | 503 | Birmingham | Alabama | United States | -86.80249 | 33.52066
Birmingham | Alabama | United States | -86.80249 | 33.52066
Birmingham | Alabama | United States | -86.80249 | 33.52066
Birmingham | Alabama | United States | -86.80249 | 33.52066
Columbiana | Alabama | United States | -86.60721 | 33.17817
Hoover | Alabama | United States | -86.81138 | 33.40539
Anchorage | Alaska | United States | -149.90028 | 61.21806
Phoenix | Arizona | United States | -112.07404 | 33.44838
Phoenix, Arizona | Arizona | United States | N/A | N/A
Beverly Hills | California | United States | -118.40036 | 34.07362
Concord | California | United States | -122.03107 | 37.97798
Glendora | California | United States | -117.86534 | 34.13612
Greenbrae | California | United States | -122.5247 | 37.94854
Irvine | California | United States | -117.82311 | 33.66946
La Jolla | California | United States | -117.2742 | 32.84727
Laguna Woods | California | United States | -117.72533 | 33.6103
Los Angelas | California | United States | N/A | N/A
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Modesto | California | United States | -120.99688 | 37.6391
Sacramento | California | United States | -121.4944 | 38.58157
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
Torrance | California | United States | -118.34063 | 33.83585
Vista | California | United States | -117.24254 | 33.20004
Aventura | Florida | United States | -80.13921 | 25.95648
Bay Pines | Florida | United States | -82.77816 | 27.81419
Coral Gables | Florida | United States | -80.26838 | 25.72149
Daytona Beach | Florida | United States | -81.02283 | 29.21081
Lake Worth | Florida | United States | -80.07231 | 26.61708
Miami | Florida | United States | -80.19366 | 25.77427
New Smyrna Beach | Florida | United States | -80.927 | 29.02582
Ocala | Florida | United States | -82.14009 | 29.1872
Orange City | Florida | United States | -81.29867 | 28.94888
Pensacola | Florida | United States | -87.21691 | 30.42131
Pinecrest | Florida | United States | -80.30811 | 25.66705
Saint Augustine | Florida | United States | -81.31452 | 29.89469
Spring Hill | Florida | United States | -82.52546 | 28.47688
St. Petersburg | Florida | United States | -82.67927 | 27.77086
St. Petersburg | Florida | United States | -82.67927 | 27.77086
Stuart | Florida | United States | -80.25283 | 27.19755
Tallahassee | Florida | United States | -84.28073 | 30.43826
Wellington | Florida | United States | -80.24144 | 26.65868
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Atlanta | Georgia | United States | -84.38798 | 33.749
Blue Ridge | Georgia | United States | -84.32409 | 34.86397
Calhoun | Georgia | United States | -84.95105 | 34.50259
Decatur | Georgia | United States | -84.29631 | 33.77483
Marietta | Georgia | United States | -84.54993 | 33.9526
Meridian | Idaho | United States | -116.39151 | 43.61211
Belleville | Illinois | United States | -89.98399 | 38.52005
Peoria | Illinois | United States | -89.58899 | 40.69365
Peoria | Illinois | United States | -89.58899 | 40.69365
Wheaton | Illinois | United States | -88.10701 | 41.86614
Winfield | Illinois | United States | -88.1609 | 41.8617
Evansville | Indiana | United States | -87.55585 | 37.97476
Jeffersonville | Indiana | United States | -85.73718 | 38.27757
Newburgh | Indiana | United States | -87.40529 | 37.94449
South Bend | Indiana | United States | -86.25001 | 41.68338
Des Moines | Iowa | United States | -93.60911 | 41.60054
Wichita | Kansas | United States | -97.33754 | 37.69224
Murray | Kentucky | United States | -88.31476 | 36.61033
Bossier City | Louisiana | United States | -93.73212 | 32.51599
Laurel | Maryland | United States | -76.84831 | 39.09928
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Picayune | Mississippi | United States | -89.67788 | 30.52556
Kansas City | Missouri | United States | -94.57857 | 39.09973
Missoula | Montana | United States | -113.994 | 46.87215
Omaha | Nebraska | United States | -95.94043 | 41.25626
Henderson | Nevada | United States | -114.98194 | 36.0397
Hillsborough | New Jersey | United States | -74.62682 | 40.4776
Perth Amboy | New Jersey | United States | -74.26542 | 40.50677
Somerville | New Jersey | United States | -74.60988 | 40.57427
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Bay Shore | New York | United States | -73.24539 | 40.7251
Garden City | New York | United States | -73.6343 | 40.72677
Great Neck | New York | United States | -73.72846 | 40.80066
Lewiston | New York | United States | -79.03588 | 43.17256
Asheboro | North Carolina | United States | -79.81364 | 35.70791
Cary | North Carolina | United States | -78.78112 | 35.79154
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Durham | North Carolina | United States | -78.89862 | 35.99403
Fayetteville | North Carolina | United States | -78.87836 | 35.05266
Greensboro | North Carolina | United States | -79.79198 | 36.07264
Salisbury | North Carolina | United States | -80.47423 | 35.67097
Bismarck | North Dakota | United States | -100.78374 | 46.80833
Bellbrook | Ohio | United States | -84.07077 | 39.63562
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Columbus | Ohio | United States | -82.99879 | 39.96118
Columbus | Ohio | United States | -82.99879 | 39.96118
Portland | Oregon | United States | -122.67621 | 45.52345
Fleetwood | Pennsylvania | United States | -75.81798 | 40.45398
Providence | Rhode Island | United States | -71.41283 | 41.82399
Nashville | Tennessee | United States | -86.78444 | 36.16589
Athes | Texas | United States | N/A | N/A
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Fort Worth | Texas | United States | -97.32085 | 32.72541
Houston | Texas | United States | -95.36327 | 29.76328
Houston | Texas | United States | -95.36327 | 29.76328
New Brunfels | Texas | United States | N/A | N/A
San Antonio | Texas | United States | -98.49363 | 29.42412
Temple | Texas | United States | -97.34278 | 31.09823
Texarkana | Texas | United States | -94.04769 | 33.42513
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Alexandria | Virginia | United States | -77.04692 | 38.80484
Bellevue | Washington | United States | -122.20068 | 47.61038
Mountlake Terrace | Washington | United States | -122.30874 | 47.78815
Seattle | Washington | United States | -122.33207 | 47.60621
Spokane | Washington | United States | -117.42908 | 47.65966
Tacoma | Washington | United States | -122.44429 | 47.25288
Buenos Aires | Buenos Aires | Argentina | N/A | N/A
Buenos Aires | Buenos Aires | Argentina | N/A | N/A
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Ciudad de Buenos Aires | N/A | Argentina | N/A | N/A
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Edegem | N/A | Belgium | 4.44504 | 51.15662
Genk | N/A | Belgium | 5.50082 | 50.965
La Louvière | N/A | Belgium | 4.18785 | 50.48657
Liège | N/A | Belgium | 5.56749 | 50.63373
Roeselare | N/A | Belgium | 3.12269 | 50.94653
Belo Horizonte | Minas Gerais | Brazil | -43.93778 | -19.92083
Rio de Janeiro | Rio de Janeiro | Brazil | -43.18223 | -22.90642
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
Porto Alegre | Rio Grande do Sul | Brazil | -51.23019 | -30.03283
São Paulo | São Paulo | Brazil | -46.63611 | -23.5475
Pleven | N/A | Bulgaria | 24.61667 | 43.41667
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Varna | N/A | Bulgaria | 27.91667 | 43.21667
Surrey | British Columbia | Canada | -122.82509 | 49.10635
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Saint John | New Brunswick | Canada | -66.05616 | 45.27076
St. John's | Newfoundland and Labrador | Canada | -52.70931 | 47.56494
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Kentville | Nova Scotia | Canada | -64.49605 | 45.0771
Barrie | Ontario | Canada | -79.66634 | 44.40011
Brantford | Ontario | Canada | -80.26636 | 43.1334
Courtice | Ontario | Canada | -78.76626 | 43.91682
Greater Sudbury | Ontario | Canada | -80.99001 | 46.49
Guelph | Ontario | Canada | -80.25599 | 43.54594
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Kingston | Ontario | Canada | -76.48098 | 44.22976
London | Ontario | Canada | -81.23304 | 42.98339
London | Ontario | Canada | -81.23304 | 42.98339
North Bay | Ontario | Canada | -79.46633 | 46.3168
Oakville | Ontario | Canada | -79.68292 | 43.45011
Oshawa | Ontario | Canada | -78.84957 | 43.90012
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Scarborough Village | Ontario | Canada | -79.22124 | 43.73899
Scarborough Village | Ontario | Canada | -79.22124 | 43.73899
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Saint-Charles-Borromée | Quebec | Canada | -73.46586 | 46.05007
Saint-Jérôme | Quebec | Canada | -74.00365 | 45.78036
Sherbrooke | Quebec | Canada | -71.89908 | 45.40008
Trois-Rivières | Quebec | Canada | -72.5477 | 46.34515
Hradec Králové | N/A | Czechia | 15.83277 | 50.20923
Ostrava - Poruba | N/A | Czechia | N/A | N/A
Prague | N/A | Czechia | 14.42076 | 50.08804
Prague | N/A | Czechia | 14.42076 | 50.08804
Prague | N/A | Czechia | 14.42076 | 50.08804
Roudnice nad Labem | N/A | Czechia | 14.26175 | 50.42528
Aalborg | N/A | Denmark | 9.9187 | 57.048
Aarhus N | N/A | Denmark | 10.17317 | 56.20367
Fredericia | N/A | Denmark | 9.75257 | 55.56568
Randers | N/A | Denmark | 10.03639 | 56.4607
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tartu | N/A | Estonia | 26.72509 | 58.38062
Tartu | N/A | Estonia | 26.72509 | 58.38062
Helsinki | N/A | Finland | 24.93545 | 60.16952
Jakobstad | N/A | Finland | 22.70256 | 63.67486
Kouvola | N/A | Finland | 26.7 | 60.86667
Kuopio | N/A | Finland | 27.67703 | 62.89238
Tampere | N/A | Finland | 23.78712 | 61.49911
Bully-les-Mines | Hauts-de-France | France | 2.72703 | 50.4438
Agny | N/A | France | 2.76002 | 50.25914
Angers | N/A | France | -0.55202 | 47.47156
Annecy | N/A | France | 6.12565 | 45.90878
Arras | N/A | France | 2.78186 | 50.29301
Athis-Mons | N/A | France | 2.39147 | 48.70522
Besançon | N/A | France | 6.01815 | 47.24878
Bouchemaine | N/A | France | -0.60888 | 47.42234
Broglie | N/A | France | 0.52915 | 49.00911
Castelneau Le Nez | N/A | France | N/A | N/A
Chambéry | N/A | France | 5.92079 | 45.56628
Chilly-Mazarin | N/A | France | 2.31638 | 48.71489
Cournonterral | N/A | France | 3.72 | 43.55889
Créteil | N/A | France | 2.46569 | 48.79266
Domarin | N/A | France | 5.24599 | 45.58662
Épinay-sur-Orge | N/A | France | 2.31074 | 48.67338
Évreux | N/A | France | 1.15082 | 49.02414
Évreux | N/A | France | 1.15082 | 49.02414
Gif-sur-Yvette | N/A | France | 2.13333 | 48.68333
Grenoble | N/A | France | 5.71479 | 45.17869
La Seyne-sur-Mer | N/A | France | 5.87816 | 43.10322
Lamarque | N/A | France | -0.71771 | 45.09615
Laval | N/A | France | -0.77019 | 48.07247
Le Brusc | N/A | France | 5.803 | 43.074
Le Kremlin-Bicêtre | N/A | France | 2.36073 | 48.81471
Les Mureaux | N/A | France | 1.90972 | 48.99173
Lesparre-Médoc | N/A | France | -0.93793 | 45.30709
Linas | N/A | France | 2.26266 | 48.63041
Longpont-sur-Orge | N/A | France | 2.29278 | 48.64171
Lyon | N/A | France | 4.84671 | 45.74846
Melun | N/A | France | 2.65356 | 48.5457
Meudon | N/A | France | 2.235 | 48.81381
Meylan | N/A | France | 5.77762 | 45.20978
Mont-de-Marsan | N/A | France | -0.49713 | 43.89022
Montauban | N/A | France | 1.3542 | 44.01759
Montpelier | N/A | France | N/A | N/A
Montpellier | N/A | France | 3.87635 | 43.61093
Montpellier | N/A | France | 3.87635 | 43.61093
Orléans | N/A | France | 1.90389 | 47.90289
Paris | N/A | France | 2.3488 | 48.85341
Pontonx Sur Adour | N/A | France | N/A | N/A
Roanne | N/A | France | 4.06802 | 46.03624
Saint-Chamond | N/A | France | 4.51294 | 45.4759
Saint-Denis | N/A | France | 2.35387 | 48.93564
Saint-Egrève | N/A | France | N/A | N/A
Saint-Galmier | N/A | France | 4.31086 | 45.59787
Saint-Georges-dOrques | N/A | France | 3.78139 | 43.61139
Saint-Germain-Lespinasse | N/A | France | 3.96503 | 46.10342
Saint-Sébastien-de-Morsent | N/A | France | 1.0873 | 49.01096
Sainte-Suzanne | N/A | France | 6.76775 | 47.50017
Sanary-sur-Mer | N/A | France | 5.80155 | 43.11985
Sarlat-la-Canéda | N/A | France | 1.21656 | 44.88902
Seysses | N/A | France | 1.31081 | 43.49801
Six-Fours-les-Plages | N/A | France | 5.82465 | 43.09174
Suresnes | N/A | France | 2.22929 | 48.87143
Toulon | N/A | France | 5.92836 | 43.12442
Tours | N/A | France | 0.70398 | 47.39484
Vaucresson | N/A | France | 2.15652 | 48.84078
Verneuil-sur-Seine | N/A | France | 1.9648 | 48.97388
Villejuif | N/A | France | 2.35992 | 48.7939
Villeneuve-lès-Maguelone | N/A | France | 3.86047 | 43.53222
Vourey | N/A | France | 5.51931 | 45.3218
Aalen | Baden-Wurttemberg | Germany | 10.0933 | 48.83777
Freiburg im Breisgau | Baden-Wurttemberg | Germany | 7.85222 | 47.9959
Konstanz | Baden-Wurttemberg | Germany | 9.17582 | 47.66033
Mosbach | Baden-Wurttemberg | Germany | 9.15106 | 49.35357
Rottweil | Baden-Wurttemberg | Germany | 8.62719 | 48.16783
Stockach | Baden-Wurttemberg | Germany | 9.0091 | 47.85105
Aichach | Bavaria | Germany | 11.13413 | 48.45755
Amberg | Bavaria | Germany | 11.86267 | 49.44287
Augsburg | Bavaria | Germany | 10.89851 | 48.37154
Graefeling | Bavaria | Germany | N/A | N/A
Neu-Ulm | Bavaria | Germany | 10.01112 | 48.39279
Schongau | Bavaria | Germany | 10.89664 | 47.8124
Wertingen | Bavaria | Germany | 10.68149 | 48.56314
Hagenow | Brandenburg | Germany | N/A | N/A
Lauchhammer | Brandenburg | Germany | 13.76623 | 51.48813
Oranienburg | Brandenburg | Germany | 13.24197 | 52.75577
Senftenberg | Brandenburg | Germany | 14.00164 | 51.52517
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Hamburg | City state of Hamburg | Germany | 9.99302 | 53.55073
Alzenau | Hesse | Germany | N/A | N/A
Frankfurt am Main | Hesse | Germany | 8.68417 | 50.11552
Fulda | Hesse | Germany | 9.67518 | 50.55162
Giessen | Hesse | Germany | 8.67554 | 50.58727
Kassel | Hesse | Germany | 9.5 | 51.31667
Koenigstein | Hesse | Germany | N/A | N/A
Marburg | Hesse | Germany | 8.77069 | 50.80904
Schwalbach | Hesse | Germany | 8.46943 | 50.49672
Delmenhorst | Lower Saxony | Germany | 8.63091 | 53.0511
Holzminden | Lower Saxony | Germany | 9.4455 | 51.82798
Oldenburg | Lower Saxony | Germany | 8.21467 | 53.14118
Osnabrück | Lower Saxony | Germany | 8.0498 | 52.27264
Grimmen | Mecklenburg-Vorpommern | Germany | 13.04051 | 54.11215
Parchim | Mecklenburg-Vorpommern | Germany | 11.84875 | 53.42631
Dülmen | North Rhine-Westphalia | Germany | 7.28075 | 51.83149
Stadtlohn | North Rhine-Westphalia | Germany | 6.91918 | 51.99399
Koblenz | Rhineland-Palatinate | Germany | 7.57883 | 50.35357
Hohenstein-Ernsttal | Saxony | Germany | N/A | N/A
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Leipzig | Saxony | Germany | 12.37129 | 51.33962
Halle | Saxony-Anhalt | Germany | 11.97947 | 51.48158
Hettstedt | Saxony-Anhalt | Germany | 11.51146 | 51.6503
Merseburg | Saxony-Anhalt | Germany | 11.98923 | 51.35478
Husum | Schleswig-Holstein | Germany | 9.05239 | 54.4858
Kiel | Schleswig-Holstein | Germany | 10.13489 | 54.32133
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Berlin | State of Berlin | Germany | 13.41053 | 52.52437
Apolda | Thuringia | Germany | 11.51638 | 51.02624
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Pátrai | N/A | Greece | 21.73444 | 38.24444
Polygyros | N/A | Greece | 23.44135 | 40.37704
Thassaloniki | N/A | Greece | N/A | N/A
Budapest | N/A | Hungary | 19.04045 | 47.49835
Sopron | N/A | Hungary | 16.59049 | 47.68501
Székesfehérvár | N/A | Hungary | 18.41034 | 47.18995
Veszprém | N/A | Hungary | 17.91149 | 47.09327
Reykjavik | N/A | Iceland | -21.89541 | 64.13548
Haifa | N/A | Israel | 34.99928 | 32.81303
Haifa | N/A | Israel | 34.99928 | 32.81303
Holon | N/A | Israel | 34.77918 | 32.01034
Kfar Saba | N/A | Israel | 34.90694 | 32.175
Ramat Gan | N/A | Israel | 34.81065 | 32.08227
Zrifin | N/A | Israel | N/A | N/A
Catanzaro | Calabria | Italy | 16.60086 | 38.88247
Avellino | Campania | Italy | 14.79103 | 40.91494
Castellamare Di Stabia (NA) | Campania | Italy | N/A | N/A
Napoli | Campania | Italy | 14.5195 | 40.87618
San Felice A Cancello Caserta | Campania | Italy | N/A | N/A
Torre Del Greco (NA) | Campania | Italy | 14.36806 | 40.78931
Modena | Emilia-Romagna | Italy | 10.92539 | 44.64783
Udine | Friuli Venezia Giulia | Italy | 13.23715 | 46.0693
Rome | Lazio | Italy | 12.51133 | 41.89193
Genoa | Liguria | Italy | 8.94439 | 44.40478
Lecco | Lombardy | Italy | 9.39704 | 45.85589
Milan | Lombardy | Italy | 9.18951 | 45.46427
Ivrea (TO) | Piedmont | Italy | 7.87617 | 45.46723
Novara | Piedmont | Italy | 8.62118 | 45.44694
Turin | Piedmont | Italy | 7.68682 | 45.07049
Cagliari | Sardinia | Italy | 9.11917 | 39.23054
Acireale (CT) | Sicily | Italy | 15.16577 | 37.60886
Bagno A Ripoli (FI) | Tuscany | Italy | 11.32252 | 43.75115
Florence | Tuscany | Italy | 11.24626 | 43.77925
Siena | Tuscany | Italy | 11.33064 | 43.31822
Portogruaro (VE) | Veneto | Italy | 12.84052 | 45.78071
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Klaipėda | N/A | Lithuania | 21.13912 | 55.7068
Klaipėda | N/A | Lithuania | 21.13912 | 55.7068
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Guadalajara | Jalisco | Mexico | -103.34749 | 20.67738
Zapopan | Jalisco | Mexico | -103.38742 | 20.72111
Zapopan, Jalisco | Jalisco | Mexico | N/A | N/A
Mexico | N/A | Mexico | -98.43784 | 18.88011
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Alkmaar | N/A | Netherlands | 4.74861 | 52.63167
Amstelveen | N/A | Netherlands | 4.86389 | 52.30083
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Arnhem | N/A | Netherlands | 5.91111 | 51.98
Doetinchem | N/A | Netherlands | 6.28889 | 51.965
Enschede | N/A | Netherlands | 6.89583 | 52.21833
Etten-Leur | N/A | Netherlands | 4.63726 | 51.57056
Groningen | N/A | Netherlands | 6.56667 | 53.21917
Groningen | N/A | Netherlands | 6.56667 | 53.21917
Heerlen | N/A | Netherlands | 5.98154 | 50.88365
Hilversum | N/A | Netherlands | 5.17639 | 52.22333
Hoofddorp | N/A | Netherlands | 4.68889 | 52.3025
Maastricht | N/A | Netherlands | 5.68889 | 50.84833
The Hague | N/A | Netherlands | 4.29861 | 52.07667
Tilburg | N/A | Netherlands | 5.0913 | 51.55551
Tilburg | N/A | Netherlands | 5.0913 | 51.55551
Veldhoven | N/A | Netherlands | 5.40278 | 51.41833
Winterswijk | N/A | Netherlands | 6.71944 | 51.9725
Zwijndrecht | N/A | Netherlands | 4.63333 | 51.8175
Ålesund | N/A | Norway | 6.15492 | 62.47225
Bergen | N/A | Norway | 5.32415 | 60.39299
Bodø | N/A | Norway | 14.37513 | 67.28267
Haugesund | N/A | Norway | 5.268 | 59.41378
Moelv | N/A | Norway | 10.7 | 60.93333
Nøtterøy | N/A | Norway | 10.4 | 59.23333
Oslo | N/A | Norway | 10.74609 | 59.91273
Oslo | N/A | Norway | 10.74609 | 59.91273
Porsgrunn | N/A | Norway | 9.6561 | 59.14054
Tønsberg | N/A | Norway | 10.40762 | 59.26754
Manila | N/A | Philippines | 120.9822 | 14.6042
Quezon City | N/A | Philippines | 121.0509 | 14.6488
Gdansk | N/A | Poland | 18.64912 | 54.35227
Krakow | N/A | Poland | 19.93658 | 50.06143
Krakow | N/A | Poland | 19.93658 | 50.06143
Lublin | N/A | Poland | 22.56667 | 51.25
Wroclaw | N/A | Poland | 17.03333 | 51.1
Abrantes | N/A | Portugal | -8.2 | 39.46667
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Porto | N/A | Portugal | -8.61099 | 41.14961
Porto | N/A | Portugal | -8.61099 | 41.14961
S. Martinho Do Bispo | N/A | Portugal | N/A | N/A
Ponce | Puerto Rico | Puerto Rico | -66.62398 | 18.01031
Santurce | Puerto Rico | Puerto Rico | -67.14018 | 18.19523
Arad | N/A | Romania | 21.31667 | 46.18333
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Cluj-Napoca | N/A | Romania | 23.6 | 46.76667
Iași | N/A | Romania | 27.6 | 47.16667
Timișoara | N/A | Romania | 21.22571 | 45.75372
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Rostov-on-Don | N/A | Russia | 39.72328 | 47.23135
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Smolensk | N/A | Russia | 32.04371 | 54.77944
Banská Bystrica | N/A | Slovakia | 19.15349 | 48.73946
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Košice | N/A | Slovakia | 21.25808 | 48.71395
Martin | N/A | Slovakia | 18.92399 | 49.06651
Skalica | N/A | Slovakia | 17.22635 | 48.8449
Žilina | N/A | Slovakia | 18.73941 | 49.22315
Cape Town | N/A | South Africa | 18.42322 | -33.92584
Claremont | N/A | South Africa | 18.46528 | -33.98056
Somerset West | N/A | South Africa | 18.82113 | -34.08401
Sunninghill | N/A | South Africa | 28.06552 | -26.0355
Pusan | N/A | South Korea | 128.3681 | 36.3809
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
A Coruña | N/A | Spain | -8.396 | 43.37135
Alava | N/A | Spain | -6.19946 | 43.36057
Alcázar de San Juan (Ciudad Real) | N/A | Spain | -3.20827 | 39.39011
Badajoz | N/A | Spain | -6.97061 | 38.87789
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Barcelona | N/A | Spain | 2.15899 | 41.38879
Burgos | N/A | Spain | -3.70184 | 42.34106
Ciudad Real | N/A | Spain | -3.92907 | 38.98626
Donostia / San Sebastian | N/A | Spain | -1.97499 | 43.31283
Elche (Alicante) | N/A | Spain | -0.70107 | 38.26218
Gijón | N/A | Spain | -5.66152 | 43.53573
Guadalajara | N/A | Spain | -3.16185 | 40.62862
Jerez de la Frontera | N/A | Spain | -6.13606 | 36.68645
Langreo (Oviedo) | N/A | Spain | -5.68416 | 43.29568
Las Palmas | N/A | Spain | -16.16555 | 28.58232
Las Palmas de Gran Canaria | N/A | Spain | -15.41343 | 28.09973
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Manacor (Palma de Mallorca) | N/A | Spain | 3.20955 | 39.56964
Marbella | N/A | Spain | -4.88583 | 36.51543
Málaga | N/A | Spain | -4.42034 | 36.72016
Mendaro, Guipuzcoa | N/A | Spain | -2.38568 | 43.25326
Mérida | N/A | Spain | -6.34366 | 38.91611
Murcia | N/A | Spain | -1.13004 | 37.98704
Palma de Mallorca | N/A | Spain | 2.65024 | 39.56939
Pamplona | N/A | Spain | -1.64323 | 42.81687
Pontevedra | N/A | Spain | -8.64435 | 42.431
Sabadell (Barcelona) | N/A | Spain | 2.10942 | 41.54329
San Sebastián | N/A | Spain | -5.9 | 43.56667
Santa Cruz de Tenerife | N/A | Spain | -16.25462 | 28.46824
Santander | N/A | Spain | -3.80444 | 43.46472
Santander | N/A | Spain | -3.80444 | 43.46472
Santiago de Compostela | N/A | Spain | -8.54569 | 42.88052
Tortosa | N/A | Spain | 0.5216 | 40.81249
Valencia | N/A | Spain | -0.37966 | 39.47391
Vigo (Pontevedra) | N/A | Spain | -8.72264 | 42.23282
Vigo/Pontevedra | N/A | Spain | N/A | N/A
Vitoria-Gasteiz | N/A | Spain | -2.67268 | 42.84998
Vizcaya | N/A | Spain | N/A | N/A
Kaohsiung City | N/A | Taiwan | 120.31333 | 22.61626
Taichung | N/A | Taiwan | 120.6839 | 24.1469
Tainan City | N/A | Taiwan | 120.21333 | 22.99083
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taoyuan District | N/A | Taiwan | 121.3187 | 24.9896
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Chiang Mai | N/A | Thailand | 98.98468 | 18.79038
Sousse | N/A | Tunisia | 10.63699 | 35.82539
Tunis | N/A | Tunisia | 10.16579 | 36.81897
Tunis | N/A | Tunisia | 10.16579 | 36.81897
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Izmir | N/A | Turkey (Türkiye) | 27.13838 | 38.41273
Sıhhiye/Ankara | N/A | Turkey (Türkiye) | N/A | N/A
Swansea | Glamorgan | United Kingdom | -3.94323 | 51.62079
Buckshaw Village, Chorley | Lancashire | United Kingdom | -2.61667 | 53.65
Northwood | Middlesex | United Kingdom | -0.42454 | 51.61162
Edinburgh | Midlothian | United Kingdom | -3.19648 | 55.95206
Oxford | Oxfordshire | United Kingdom | -1.25596 | 51.75222
Chichester | Sussex West | United Kingdom | -0.78003 | 50.83673
Clydebank, Glasgow | N/A | United Kingdom | N/A | N/A
Dundee | N/A | United Kingdom | -2.97489 | 56.46913
Edgbaston, Birmingham | N/A | United Kingdom | N/A | N/A
Manchester | N/A | United Kingdom | -2.23743 | 53.48095
Waterloo, Liverpool | N/A | United Kingdom | N/A | N/A
N/A | N/A | N/A | N/A | N/A | 4,844 | 1 | 0.000206 | 0 | NCT00090103 | 1COMPLETED | 2009-04-01 | 2003-11-01 | GlaxoSmithKline | 4INDUSTRY | false | false | false | null | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000036 |
[
4
] | 1,913 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | false | Subjects who qualify for participation will receive lenalidomide with or without dexamethasone in 4 week cycles until disease progression is documented or lenalidomide becomes commercially available for the indication of multiple myeloma. | This was a multicenter, non-randomized, open-label, uncontrolled, single-arm treatment study of lenalidomide as monotherapy or in combination with dexamethasone in subjects with previously treated relapsed or refractory multiple myeloma, with measurable myeloma paraprotein in serum and/or urine. Subjects who met all of the eligibility criteria were enrolled into the study. Screening procedures took place within 28 days of first dose. Subjects who qualified for participation received oral lenalidomide at a dose of 25 mg daily for 21 days every 28 days.
Subjects had the following options for dexamethasone treatment at the discretion of the treating physician:
Option A: No dexamethasone.
Option B: Oral pulse dexamethasone administered at a dose of 40 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle.
Option C: Oral pulse dexamethasone administered at a dose of 20 mg daily on Days 1-4, 9-12, and 17-20 for each 28-day cycle.
Option D: Oral dexamethasone administered at a dose of 40 mg weekly on Days 1, 8, 15, and 22 for each 28-day cycle for all cycles. Treatment was to be continued as tolerated until disease progression developed.
Doses of lenalidomide were allowed to be reduced first from 25 mg to 15 mg and then in 5-mg decrements due to lenalidomide toxicity. Subjects who could not tolerate a daily dose of 5 mg for 21 days every 28 days were discontinued from treatment. At the discretion of the investigator, doses of dexamethasone were modified due to dexamethasone toxicity. Dose reduction and discontinuation schemes for dexamethasone varied according to the treatment option administered.
Study visits occurred every 2 weeks for the first 3 cycles of therapy and then every 4 weeks after the third cycle until disease progression was documented, study drug was discontinued for another reason, or lenalidomide became commercially available for this indication. | Multiple Myeloma | Multiple Myeloma MM Revlimid CC5013 celgene cc-5013 relapsed/refractory lenalidomide dexamethasone Decadron | null | 1 | arm 1: single-arm, open-label, lenalidomide, 5-25 mg, 21/28 days, with/without dexamethasone | [
5
] | 2 | [
0,
0
] | intervention 1: Lenalidomide, 5 mg to 25 mg, QD, orally, for 21 days every 28 days, with or without dexamethasone intervention 2: Dexamethasone, 20 mg to 40 mg, QD, orally, administered under a variety of dosing regimens | intervention 1: lenalidomide intervention 2: dexamethasone | 69 | Scottsdale | Arizona | United States | -111.89903 | 33.50921
Berkeley | California | United States | -122.27275 | 37.87159
La Jolla | California | United States | -117.2742 | 32.84727
Los Angeles | California | United States | -118.24368 | 34.05223
San Diego | California | United States | -117.16472 | 32.71571
Stanford | California | United States | -122.16608 | 37.42411
Vallejo | California | United States | -122.25664 | 38.10409
Aurora | Colorado | United States | -104.83192 | 39.72943
Denver | Colorado | United States | -104.9847 | 39.73915
New Haven | Connecticut | United States | -72.92816 | 41.30815
Stamford | Connecticut | United States | -73.53873 | 41.05343
Newark | Delaware | United States | -75.74966 | 39.68372
Miami | Florida | United States | -80.19366 | 25.77427
Miami Beach | Florida | United States | -80.13005 | 25.79065
St. Petersburg | Florida | United States | -82.67927 | 27.77086
Tampa | Florida | United States | -82.45843 | 27.94752
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Atlanta | Georgia | United States | -84.38798 | 33.749
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Kansas City | Kansas | United States | -94.62746 | 39.11417
Wichita | Kansas | United States | -97.33754 | 37.69224
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Baltimore | Maryland | United States | -76.61219 | 39.29038
Bethesda | Maryland | United States | -77.10026 | 38.98067
Boston | Massachusetts | United States | -71.05977 | 42.35843
Rochester | Minnesota | United States | -92.4699 | 44.02163
Jackson | Mississippi | United States | -90.18481 | 32.29876
St Louis | Missouri | United States | -90.19789 | 38.62727
Billings | Montana | United States | -108.50069 | 45.78329
Omaha | Nebraska | United States | -95.94043 | 41.25626
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Lebanon | New Hampshire | United States | -72.25176 | 43.64229
Hackensack | New Jersey | United States | -74.04347 | 40.88593
Brooklyn | New York | United States | -73.94958 | 40.6501
East Setauket | New York | United States | -73.10594 | 40.94149
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Syracuse | New York | United States | -76.14742 | 43.04812
The Bronx | New York | United States | -73.86641 | 40.84985
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Fargo | North Dakota | United States | -96.7898 | 46.87719
Columbus | Ohio | United States | -82.99879 | 39.96118
Portland | Oregon | United States | -122.67621 | 45.52345
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Charleston | South Carolina | United States | -79.93275 | 32.77632
Charleston | South Carolina | United States | -79.93275 | 32.77632
Columbia | South Carolina | United States | -81.03481 | 34.00071
Sioux Falls | South Dakota | United States | -96.70033 | 43.54997
Dallas | Texas | United States | -96.80667 | 32.78306
Houston | Texas | United States | -95.36327 | 29.76328
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Richmond | Virginia | United States | -77.46026 | 37.55376
Seattle | Washington | United States | -122.33207 | 47.60621
Seattle | Washington | United States | -122.33207 | 47.60621
La Crosse | Wisconsin | United States | -91.23958 | 43.80136
Marshfield | Wisconsin | United States | -90.1718 | 44.66885
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Calgary | Alberta | Canada | -114.08529 | 51.05011
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Vancouver | British Columbia | Canada | -123.11934 | 49.24966
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Toronto | Ontario | Canada | -79.39864 | 43.70643
Montreal | Quebec | Canada | -73.58781 | 45.50884 | 1,913 | 10 | 0.005227 | 1 | NCT00179647 | 1COMPLETED | 2009-04-01 | 2005-09-01 | Celgene Corporation | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.002842 |
[
3
] | 65 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 1FEMALE | false | Gemcitabine and anthracycline combination has shown encouraging activity as neoadjuvant chemotherapy in locally advanced breast cancer. An addition of sequential gemcitabine and cisplatin, also a highly active combination in this indication, may result in improvement in pathological response and overall survival. Patients with operable breast cancer will be treated in neoadjuvant setting with gemcitabine plus doxorubicin, followed by gemcitabine plus cisplatin. | null | Breast Cancer | null | 1 | arm 1: Gemcitabine: 1200 mg/m\^2, intravenous (IV) day 1 and day 8 every 21 days x 4 cycles (1-4) then 1000 mg/m\^2, IV, day 1 and day 8 every 21 days x 4 cycles (5-8).
Doxorubicin: 60 mg/m\^2, IV, every 21 days x 4 cycles (1-4). Cisplatin: 70 mg/m\^2, IV, every 21 days x 4 cycles (5-8). Surgery follows 8 cycles of chemotherapy. Extent and type of surgery is guided by tumor size, physician and/or patient decision. | [
0
] | 4 | [
0,
0,
0,
3
] | intervention 1: 1200 mg/m\^2, intravenous (IV) day 1 and day 8 every 21 days x 4 cycles (1-4) then 1000 mg/m\^2, IV, day 1 and day 8 every 21 days x 4 cycles (5-8) intervention 2: 60 mg/m\^2, IV, every 21 days x 4 cycles (1-4) intervention 3: 70 mg/m\^2, IV, every 21 days x 4 cycles (5-8) intervention 4: Surgery follows 8 cycles of chemotherapy. Extent and type of surgery is guided by tumor size, physician and/or patient decision. | intervention 1: gemcitabine intervention 2: doxorubicin intervention 3: cisplatin intervention 4: surgery | 3 | Pune | Maharashtra | India | 73.85535 | 18.51957
Vellore | Tamil Nadu | India | 79.13255 | 12.9184
Delhi | N/A | India | 77.23149 | 28.65195 | 65 | 1 | 0.015385 | 1 | NCT00191789 | 1COMPLETED | 2009-04-01 | 2003-02-01 | Eli Lilly and Company | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.002721 | |
[
4
] | 626 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | null | The study investigates the efficacy of long-term treatment of esomeprazole compared to anti-reflux surgery in the control of gastroesophageal reflux disease by assessing time to treatment failure. | null | Gastroesophageal Reflux | Acid reflux disease Gastroesophageal Reflux Disease | null | 2 | arm 1: Surgery arm 2: Esomeprazole (NEXIUM) therapy | [
1,
0
] | 2 | [
0,
3
] | intervention 1: 40 mg oral tablet administered daily intervention 2: Surgery | intervention 1: esomeprazole intervention 2: Laparoscopic fundoplication (surgery) | 59 | Linz | N/A | Austria | 14.28611 | 48.30639
Vienna | N/A | Austria | 16.37208 | 48.20849
Zell am See | N/A | Austria | 12.79839 | 47.32306
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels (Anderlecht) | N/A | Belgium | 4.34878 | 50.85045
Brussels (Woluwé-St-Lambert) | N/A | Belgium | 4.34878 | 50.85045
Ghent | N/A | Belgium | 3.71667 | 51.05
Haine-Saint-Paul | N/A | Belgium | 4.1885 | 50.45544
Leuven | N/A | Belgium | 4.70093 | 50.87959
Liège | N/A | Belgium | 5.56749 | 50.63373
Rimavska Sobota | N/A | Belgium | N/A | N/A
Århus C | N/A | Denmark | N/A | N/A
Glostrup Municipality | N/A | Denmark | 12.40377 | 55.6666
Herning | N/A | Denmark | 8.97662 | 56.13615
Hillerød | N/A | Denmark | 12.30081 | 55.92791
Hvidovre | N/A | Denmark | 12.47708 | 55.64297
Kolding | N/A | Denmark | 9.47216 | 55.4904
Odense C | N/A | Denmark | 10.39538 | 55.40841
Viborg | N/A | Denmark | 9.40201 | 56.45319
Kuopio | N/A | Finland | 27.67703 | 62.89238
Tampere | N/A | Finland | 23.78712 | 61.49911
Bordeaux | N/A | France | -0.5805 | 44.84044
Créteil | N/A | France | 2.46569 | 48.79266
Grenoble | N/A | France | 5.71479 | 45.17869
Nantes | N/A | France | -1.55336 | 47.21725
Nice | N/A | France | 7.26608 | 43.70313
Nîmes | N/A | France | 4.35788 | 43.83665
Rouen | N/A | France | 1.09932 | 49.44313
Cologne | N/A | Germany | 6.95 | 50.93333
Dresden | N/A | Germany | 13.73832 | 51.05089
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Hamburg | N/A | Germany | 9.99302 | 53.55073
Heidelberg | N/A | Germany | 8.69079 | 49.40768
Herne | N/A | Germany | 7.22572 | 51.5388
München | N/A | Germany | 13.31243 | 51.60698
Tübingen | N/A | Germany | 9.05222 | 48.52266
Wiesbaden | N/A | Germany | 8.24932 | 50.08258
Würzburg | N/A | Germany | 9.95121 | 49.79391
Reykjavik | N/A | Iceland | -21.89541 | 64.13548
Brescia | N/A | Italy | 10.21472 | 45.53558
Florence | N/A | Italy | 11.24626 | 43.77925
Modena | N/A | Italy | 10.92539 | 44.64783
Monfalcone | N/A | Italy | 13.53292 | 45.80463
Padua | N/A | Italy | 11.88586 | 45.40797
Perugia | N/A | Italy | 12.38878 | 43.1122
Pisa | N/A | Italy | 10.4036 | 43.70853
Rozzano | N/A | Italy | 9.1559 | 45.38193
San Donato Milanese | N/A | Italy | 9.26838 | 45.41047
Torino | N/A | Italy | 11.99138 | 44.88856
Utrecht | N/A | Netherlands | 5.12222 | 52.09083
Bergen | N/A | Norway | 5.32415 | 60.39299
Bodø | N/A | Norway | 14.37513 | 67.28267
Kristiansand | N/A | Norway | 7.9956 | 58.14671
Oslo | N/A | Norway | 10.74609 | 59.91273
Tromsø | N/A | Norway | 18.95508 | 69.6489
Trondheim | N/A | Norway | 10.39506 | 63.43049
Gothenburg | N/A | Sweden | 11.96679 | 57.70716
Lund | N/A | Sweden | 13.19321 | 55.70584
Salford | N/A | United Kingdom | -2.29042 | 53.48771 | 554 | 1 | 0.001805 | 1 | NCT00251927 | 1COMPLETED | 2009-04-01 | 2001-10-01 | AstraZeneca | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000319 |
[
5
] | 167 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | false | The purpose of this study is to evaluate risperidone long-acting injection (an antipsychotic medication) versus oral antipsychotics in schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) participants with a history of being poorly compliant with taking their medication. | This is a Phase 4, an open-label (all people know the identity of the intervention), multi-country and multi-centric (conducted in more than one center) study of risperidone long-acting formulation versus oral (having to do with the mouth) atypical antipsychotics in participants with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text revision ( DSM-IV TR) diagnosis of schizophrenia currently being treated with oral antipsychotic medication. The duration of this study will be 2 years. All the eligible participants will be randomly assigned to an oral atypical antipsychotic (risperidone, olanzapine, quetiapine, and where commercially available, aripiprazole and amisulpride) or to risperidone long-acting formulation. For risperidone long-acting formulation participants, study medication will be administered by intramuscular (into the muscle) injection every 2 weeks at doses of 25, 37.5 or 50 milligram (mg). Oral supplementation with the current oral atypical antipsychotic is required for the first 3 weeks following the initial injection and dose increase. Dose increase can be made as per product labeling. The primary measure of effectiveness is the reduction in the percentage of participants experiencing a clinical exacerbation after being in the study for 3 months. Participants' safety will be monitored throughout the study. | Schizophrenia | Schizophrenia Risperidone Risperdal Consta | null | 2 | arm 1: Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection will be administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic will also be administered in the first 3 weeks following the dose increase. Duration of treatment will be 24 months. arm 2: Oral atypical antipsychotic will be administered as per local label practice for 24 months. Participants will be switched to another atypical oral therapy as per Investigator's discretion. | [
0,
1
] | 2 | [
0,
0
] | intervention 1: Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection will be administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic will also be administered in the first 3 weeks following the dose increase. Duration of treatment will be 24 months. intervention 2: Oral atypical antipsychotic will be administered as per local label practice for 24 months. Participants will be switched to another atypical oral therapy as per Investigator's discretion. | intervention 1: Risperidone long-acting injection (LAI) intervention 2: Oral atypical Antipsychotic | 44 | Dandenong | N/A | Australia | 145.2 | -37.98333
Frankston | N/A | Australia | 145.12291 | -38.14458
Mount Claremont | N/A | Australia | 115.78337 | -31.96177
Newcastle | N/A | Australia | 151.7801 | -32.92953
Southport | N/A | Australia | 153.39796 | -27.96724
Calgary | Alberta | Canada | -114.08529 | 51.05011
Bathurst | New Brunswick | Canada | -65.65112 | 47.61814
Kentville | Nova Scotia | Canada | -64.49605 | 45.0771
Sydney | Nova Scotia | Canada | -60.1831 | 46.1351
Greater Sudbury | Ontario | Canada | -80.99001 | 46.49
Kingston | Ontario | Canada | -76.48098 | 44.22976
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Beauport | Quebec | Canada | -71.19201 | 46.85884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Québec | Quebec | Canada | -71.21454 | 46.81228
Saint-Georges | Quebec | Canada | -70.66526 | 46.11353
Battleford | Saskatchewan | Canada | -108.3091 | 52.73486
Prince Albert | Saskatchewan | Canada | -105.76772 | 53.20008
Montreal | N/A | Canada | -73.58781 | 45.50884
Saint John | N/A | Canada | -66.05616 | 45.27076
Co.Mayo | N/A | Ireland | N/A | N/A
Dublin | N/A | Ireland | -6.24889 | 53.33306
Mullingar | N/A | Ireland | -7.3385 | 53.52466
Birmingham | N/A | United Kingdom | -1.89983 | 52.48142
Boston | N/A | United Kingdom | -0.02664 | 52.97633
Bristol | N/A | United Kingdom | -2.59665 | 51.45523
Burnley | N/A | United Kingdom | -2.23333 | 53.8
Darwen | N/A | United Kingdom | -2.46494 | 53.69803
Devon | N/A | United Kingdom | N/A | N/A
Grantham | N/A | United Kingdom | -0.64184 | 52.91149
Leicester | N/A | United Kingdom | -1.13169 | 52.6386
Lincoln | N/A | United Kingdom | -0.53792 | 53.22683
London | N/A | United Kingdom | -0.12574 | 51.50853
Morpeth | N/A | United Kingdom | -1.68893 | 55.16882
Newcastle upon Tyne | N/A | United Kingdom | -1.61396 | 54.97328
Northampton | N/A | United Kingdom | -0.88333 | 52.25
Nottingham | N/A | United Kingdom | -1.15047 | 52.9536
Preston | N/A | United Kingdom | -2.70452 | 53.76282
Stamford | N/A | United Kingdom | -0.48333 | 52.65
Stockton-Upon-Tees | N/A | United Kingdom | N/A | N/A
Swansea | N/A | United Kingdom | -3.94323 | 51.62079
Teignmouth | N/A | United Kingdom | -3.49671 | 50.54581
Wallsend | N/A | United Kingdom | -1.53397 | 54.99111
Weston-super-Mare | N/A | United Kingdom | -2.97665 | 51.34603 | 167 | 4 | 0.023952 | 1 | NCT00256997 | 6TERMINATED | 2009-04-01 | 2006-01-01 | Janssen-Ortho Inc., Canada | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.009353 |
[
4
] | 18,113 | RANDOMIZED | PARALLEL | 1PREVENTION | null | false | 0ALL | null | The primary objective of this trial is to demonstrate the efficacy and safety of dabigatran etexilate in patients with non-valvular atrial fibrillation for the prevention of stroke and systemic embolism. | null | Atrial Fibrillation Stroke | null | 3 | arm 1: twice a day arm 2: once a day arm 3: twice a day | [
1,
1,
1
] | 3 | [
0,
0,
0
] | intervention 1: once a day intervention 2: twice daily intervention 3: twice a day | intervention 1: warfarin intervention 2: Dabigatran dose 1 intervention 3: Dabigatran dose 2 | 984 | Birmingham | Alabama | United States | -86.80249 | 33.52066
Birmingham | Alabama | United States | -86.80249 | 33.52066
Birmingham | Alabama | United States | -86.80249 | 33.52066
Birmingham | Alabama | United States | -86.80249 | 33.52066
Huntsville | Alabama | United States | -86.58594 | 34.7304
Mobile | Alabama | United States | -88.04305 | 30.69436
Lake Havasu City | Arizona | United States | -114.32245 | 34.4839
Peoria | Arizona | United States | -112.23738 | 33.5806
Tucson | Arizona | United States | -110.92648 | 32.22174
Tucson | Arizona | United States | -110.92648 | 32.22174
Hot Springs | Arkansas | United States | -93.05518 | 34.5037
Jonesboro | Arkansas | United States | -90.70428 | 35.8423
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Little Rock | Arkansas | United States | -92.28959 | 34.74648
Anaheim | California | United States | -117.9145 | 33.83529
Carmichael | California | United States | -121.32828 | 38.61713
French Camp | California | United States | -121.27106 | 37.88409
Fullerton | California | United States | -117.92534 | 33.87029
La Jolla | California | United States | -117.2742 | 32.84727
La Mesa | California | United States | -117.02308 | 32.76783
Lancaster | California | United States | -118.13674 | 34.69804
Larkspur | California | United States | -122.53525 | 37.93409
Loma Linda | California | United States | -117.26115 | 34.04835
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Mather | California | United States | -119.85573 | 37.88215
Merced | California | United States | -120.48297 | 37.30216
Oakland | California | United States | -122.2708 | 37.80437
Oceanside | California | United States | -117.37948 | 33.19587
Palm Springs | California | United States | -116.54529 | 33.8303
Pasadena | California | United States | -118.14452 | 34.14778
Redondo Beach | California | United States | -118.38841 | 33.84918
Riverside | California | United States | -117.39616 | 33.95335
Sacramento | California | United States | -121.4944 | 38.58157
Sacramento | California | United States | -121.4944 | 38.58157
Sacramento | California | United States | -121.4944 | 38.58157
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
Santa Ana | California | United States | -117.86783 | 33.74557
Santa Rosa | California | United States | -122.71443 | 38.44047
Sylmar | California | United States | -118.44925 | 34.30778
Torrance | California | United States | -118.34063 | 33.83585
Walnut Creek | California | United States | -122.06496 | 37.90631
Aurora | Colorado | United States | -104.83192 | 39.72943
Colorado Springs | Colorado | United States | -104.82136 | 38.83388
Colorado Springs | Colorado | United States | -104.82136 | 38.83388
Denver | Colorado | United States | -104.9847 | 39.73915
Denver | Colorado | United States | -104.9847 | 39.73915
Fort Collins | Colorado | United States | -105.08442 | 40.58526
Greeley | Colorado | United States | -104.70913 | 40.42331
Bridgeport | Connecticut | United States | -73.18945 | 41.17923
Bridgeport | Connecticut | United States | -73.18945 | 41.17923
Bridgeport | Connecticut | United States | -73.18945 | 41.17923
Fairfield | Connecticut | United States | -73.26373 | 41.14121
Guilford | Connecticut | United States | -72.68176 | 41.28899
Newark | Delaware | United States | -75.74966 | 39.68372
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Atlantis | Florida | United States | -80.10088 | 26.5909
Boynton Beach | Florida | United States | -80.06643 | 26.52535
Brandon | Florida | United States | -82.28592 | 27.9378
Clearwater | Florida | United States | -82.8001 | 27.96585
Clearwater | Florida | United States | -82.8001 | 27.96585
Clearwater | Florida | United States | -82.8001 | 27.96585
Daytona Beach | Florida | United States | -81.02283 | 29.21081
Deerfield Beach | Florida | United States | -80.09977 | 26.31841
Fort Myers | Florida | United States | -81.84059 | 26.62168
Gainesville | Florida | United States | -82.32483 | 29.65163
Hollywood | Florida | United States | -80.14949 | 26.0112
Hollywood | Florida | United States | -80.14949 | 26.0112
Inverness | Florida | United States | -82.33037 | 28.83582
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville Beach | Florida | United States | -81.39314 | 30.29469
Lakeland | Florida | United States | -81.9498 | 28.03947
Melbourne | Florida | United States | -80.60811 | 28.08363
Melbourne | Florida | United States | -80.60811 | 28.08363
Miami | Florida | United States | -80.19366 | 25.77427
Miami | Florida | United States | -80.19366 | 25.77427
Orlando | Florida | United States | -81.37924 | 28.53834
Ormond Beach | Florida | United States | -81.05589 | 29.28581
Pensacola | Florida | United States | -87.21691 | 30.42131
Pensacola | Florida | United States | -87.21691 | 30.42131
Pensacola | Florida | United States | -87.21691 | 30.42131
Pensacola | Florida | United States | -87.21691 | 30.42131
Port Charlotte | Florida | United States | -82.09064 | 26.97617
Port Charlotte | Florida | United States | -82.09064 | 26.97617
Port Charlotte | Florida | United States | -82.09064 | 26.97617
Rockledge | Florida | United States | -80.72533 | 28.35084
Safety Harbor | Florida | United States | -82.69316 | 27.99085
Sarasota | Florida | United States | -82.53065 | 27.33643
Sarasota | Florida | United States | -82.53065 | 27.33643
St. Petersburg | Florida | United States | -82.67927 | 27.77086
St. Petersburg | Florida | United States | -82.67927 | 27.77086
Stuart | Florida | United States | -80.25283 | 27.19755
Tamarac | Florida | United States | -80.24977 | 26.21286
Tampa | Florida | United States | -82.45843 | 27.94752
Tampa | Florida | United States | -82.45843 | 27.94752
Tampa | Florida | United States | -82.45843 | 27.94752
Vero Beach | Florida | United States | -80.39727 | 27.63864
Atlanta | Georgia | United States | -84.38798 | 33.749
Atlanta | Georgia | United States | -84.38798 | 33.749
Atlanta | Georgia | United States | -84.38798 | 33.749
Augusta | Georgia | United States | -81.97484 | 33.47097
Augusta | Georgia | United States | -81.97484 | 33.47097
Blue Ridge | Georgia | United States | -84.32409 | 34.86397
Conyers | Georgia | United States | -84.01769 | 33.66761
Coeur d'Alene | Idaho | United States | -116.78047 | 47.67768
Berwyn | Illinois | United States | -87.79367 | 41.85059
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Evanston | Illinois | United States | -87.69006 | 42.04114
Glenview | Illinois | United States | -87.78784 | 42.06975
Hines | Illinois | United States | -87.8395 | 41.85364
Maywood | Illinois | United States | -87.84312 | 41.8792
Melrose Park | Illinois | United States | -87.85673 | 41.90059
Normal | Illinois | United States | -88.99063 | 40.5142
North Chicago | Illinois | United States | -87.84118 | 42.32558
Oak Lawn | Illinois | United States | -87.75811 | 41.71087
Rockford | Illinois | United States | -89.094 | 42.27113
Winfield | Illinois | United States | -88.1609 | 41.8617
Evansville | Indiana | United States | -87.55585 | 37.97476
Fort Wayne | Indiana | United States | -85.12886 | 41.1306
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Jeffersonville | Indiana | United States | -85.73718 | 38.27757
South Bend | Indiana | United States | -86.25001 | 41.68338
Dubuque | Iowa | United States | -90.66457 | 42.50056
West Des Moines | Iowa | United States | -93.71133 | 41.57721
West Des Moines | Iowa | United States | -93.71133 | 41.57721
West Des Moines | Iowa | United States | -93.71133 | 41.57721
Wichita | Kansas | United States | -97.33754 | 37.69224
Bowling Green | Kentucky | United States | -86.4436 | 36.99032
Crestview Hills | Kentucky | United States | -84.58494 | 39.02728
Lexington | Kentucky | United States | -84.47772 | 37.98869
Louisville | Kentucky | United States | -85.75941 | 38.25424
Louisville | Kentucky | United States | -85.75941 | 38.25424
Owensboro | Kentucky | United States | -87.11333 | 37.77422
Baton Rouge | Louisiana | United States | -91.18747 | 30.44332
Baton Rouge | Louisiana | United States | -91.18747 | 30.44332
Baton Rouge | Louisiana | United States | -91.18747 | 30.44332
Covington | Louisiana | United States | -90.10042 | 30.47549
Lacombe | Louisiana | United States | -89.94313 | 30.31353
Lafayette | Louisiana | United States | -92.01984 | 30.22409
Lafayette | Louisiana | United States | -92.01984 | 30.22409
Morgan City | Louisiana | United States | -91.20677 | 29.69937
New Iberia | Louisiana | United States | -91.81873 | 30.00354
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Shreveport | Louisiana | United States | -93.75018 | 32.52515
Auburn | Maine | United States | -70.23117 | 44.09785
Scarborough | Maine | United States | -70.32172 | 43.57814
Annapolis | Maryland | United States | -76.49184 | 38.97859
Annapolis | Maryland | United States | -76.49184 | 38.97859
Baltimore | Maryland | United States | -76.61219 | 39.29038
Baltimore | Maryland | United States | -76.61219 | 39.29038
Baltimore | Maryland | United States | -76.61219 | 39.29038
Baltimore | Maryland | United States | -76.61219 | 39.29038
Baltimore | Maryland | United States | -76.61219 | 39.29038
Bel Air | Maryland | United States | -76.34829 | 39.53594
Columbia | Maryland | United States | -76.83942 | 39.24038
Rockville | Maryland | United States | -77.15276 | 39.084
Salisbury | Maryland | United States | -75.59937 | 38.36067
Salisbury | Maryland | United States | -75.59937 | 38.36067
Takoma Park | Maryland | United States | -77.00748 | 38.97789
Towson | Maryland | United States | -76.60191 | 39.4015
Westminster | Maryland | United States | -76.99581 | 39.57538
Ayer | Massachusetts | United States | -71.58979 | 42.5612
Boston | Massachusetts | United States | -71.05977 | 42.35843
East Bridgewater | Massachusetts | United States | -70.95921 | 42.03343
Haverhill | Massachusetts | United States | -71.07728 | 42.7762
Haverhill | Massachusetts | United States | -71.07728 | 42.7762
Natick | Massachusetts | United States | -71.3495 | 42.28343
Newtown | Massachusetts | United States | -70.43864 | 41.67178
North Dartmouth | Massachusetts | United States | -70.97032 | 41.63899
Northborough | Massachusetts | United States | -71.64118 | 42.31954
Worcester | Massachusetts | United States | -71.80229 | 42.26259
Bloomfield Hills | Michigan | United States | -83.24549 | 42.58364
Detroit | Michigan | United States | -83.04575 | 42.33143
Grand Blanc | Michigan | United States | -83.62995 | 42.92753
Grand Rapids | Michigan | United States | -85.66809 | 42.96336
Kalamazoo | Michigan | United States | -85.58723 | 42.29171
Lapeer | Michigan | United States | -83.31883 | 43.05142
Muskegon | Michigan | United States | -86.24839 | 43.23418
Petoskey | Michigan | United States | -84.95533 | 45.37334
Rochester Hills | Michigan | United States | -83.14993 | 42.65837
Saginaw | Michigan | United States | -83.95081 | 43.41947
Troy | Michigan | United States | -83.14993 | 42.60559
Ypsilanti | Michigan | United States | -83.61299 | 42.24115
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Minneapolis | Minnesota | United States | -93.26384 | 44.97997
Robbinsdale | Minnesota | United States | -93.33856 | 45.03219
Saint Paul | Minnesota | United States | -93.09327 | 44.94441
Gulfport | Mississippi | United States | -89.09282 | 30.36742
Tupelo | Mississippi | United States | -88.70464 | 34.25807
Columbia | Missouri | United States | -92.33407 | 38.95171
Columbia | Missouri | United States | -92.33407 | 38.95171
Kansas City | Missouri | United States | -94.57857 | 39.09973
Kansas City | Missouri | United States | -94.57857 | 39.09973
Saint Charles | Missouri | United States | -90.48123 | 38.78394
St Louis | Missouri | United States | -90.19789 | 38.62727
Kalispell | Montana | United States | -114.31291 | 48.19579
Alliance | Nebraska | United States | -102.87215 | 42.10163
Omaha | Nebraska | United States | -95.94043 | 41.25626
Papillion | Nebraska | United States | -96.04224 | 41.15444
Henderson | Nevada | United States | -114.98194 | 36.0397
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Las Vegas | Nevada | United States | -115.13722 | 36.17497
Lebanon | New Hampshire | United States | -72.25176 | 43.64229
Browns Mills | New Jersey | United States | -74.58293 | 39.97261
Cherry Hill | New Jersey | United States | -75.03073 | 39.93484
Elmer | New Jersey | United States | -75.17018 | 39.59511
Englewood | New Jersey | United States | -73.97264 | 40.89288
Flemington | New Jersey | United States | -74.85933 | 40.51233
Haddon Heights | New Jersey | United States | -75.06462 | 39.87734
New Brunswick | New Jersey | United States | -74.45182 | 40.48622
Oakland | New Jersey | United States | -74.26431 | 41.01315
Ocean City | New Jersey | United States | -74.5746 | 39.27762
Paterson | New Jersey | United States | -74.17181 | 40.91677
Voorhees Township | New Jersey | United States | -74.49062 | 40.4795
Westwood | New Jersey | United States | -74.03264 | 40.99121
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Albany | New York | United States | -73.75623 | 42.65258
Buffalo | New York | United States | -78.87837 | 42.88645
Cortlandt Manor | New York | United States | -73.87164 | 41.28
Flushing | New York | United States | -73.81736 | 40.76538
Garden City | New York | United States | -73.6343 | 40.72677
Kingston | New York | United States | -73.99736 | 41.92704
Mineola | New York | United States | -73.64068 | 40.74927
Mineola | New York | United States | -73.64068 | 40.74927
New Hyde Park | New York | United States | -73.68791 | 40.7351
New Rochelle | New York | United States | -73.78235 | 40.91149
New York | New York | United States | -74.00597 | 40.71427
North Massapequa | New York | United States | -73.46207 | 40.70093
Northport | New York | United States | -73.34317 | 40.90093
Poughkeepsie | New York | United States | -73.92097 | 41.70037
Rochester | New York | United States | -77.61556 | 43.15478
Rochester | New York | United States | -77.61556 | 43.15478
Scarsdale | New York | United States | -73.78458 | 41.0051
The Bronx | New York | United States | -73.86641 | 40.84985
The Bronx | New York | United States | -73.86641 | 40.84985
Troy | New York | United States | -73.69179 | 42.72841
Watertown | New York | United States | -75.91076 | 43.97478
Williamsville | New York | United States | -78.73781 | 42.96395
Asheville | North Carolina | United States | -82.55402 | 35.60095
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Charlotte | North Carolina | United States | -80.84313 | 35.22709
Gastonia | North Carolina | United States | -81.1873 | 35.26208
Greensboro | North Carolina | United States | -79.79198 | 36.07264
High Point | North Carolina | United States | -80.00532 | 35.95569
Lexington | North Carolina | United States | -80.25338 | 35.82403
Pinehurst | North Carolina | United States | -79.46948 | 35.19543
Statesville | North Carolina | United States | -80.8873 | 35.78264
Statesville | North Carolina | United States | -80.8873 | 35.78264
Wilmington | North Carolina | United States | -77.94604 | 34.23556
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Grand Forks | North Dakota | United States | -97.03285 | 47.92526
Jamestown | North Dakota | United States | -98.70844 | 46.91054
Akron | Ohio | United States | -81.51901 | 41.08144
Canal Fulton | Ohio | United States | -81.59762 | 40.88978
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cleveland | Ohio | United States | -81.69541 | 41.4995
Cleveland | Ohio | United States | -81.69541 | 41.4995
Columbus | Ohio | United States | -82.99879 | 39.96118
Dayton | Ohio | United States | -84.19161 | 39.75895
Fairview Park | Ohio | United States | -81.8643 | 41.44144
Kettering | Ohio | United States | -84.16883 | 39.6895
Lorain | Ohio | United States | -82.18237 | 41.45282
Lyndhurst | Ohio | United States | -81.48873 | 41.52005
Sandusky | Ohio | United States | -82.70796 | 41.44894
Westlake | Ohio | United States | -81.91792 | 41.45532
Bartlesville | Oklahoma | United States | -95.98082 | 36.74731
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Corvallis | Oregon | United States | -123.26204 | 44.56457
Eugene | Oregon | United States | -123.08675 | 44.05207
Hillsboro | Oregon | United States | -122.98983 | 45.52289
Portland | Oregon | United States | -122.67621 | 45.52345
Springfield | Oregon | United States | -123.02203 | 44.04624
Allentown | Pennsylvania | United States | -75.49018 | 40.60843
Altoona | Pennsylvania | United States | -78.39474 | 40.51868
Camp Hill | Pennsylvania | United States | -76.91997 | 40.23981
Hershey | Pennsylvania | United States | -76.65025 | 40.28592
Jenkintown | Pennsylvania | United States | -75.12517 | 40.09594
Jersey Shore | Pennsylvania | United States | -77.26442 | 41.20202
Lancaster | Pennsylvania | United States | -76.30551 | 40.03788
Langhorne | Pennsylvania | United States | -74.92267 | 40.17455
Meadowbrook | Pennsylvania | United States | -79.7156 | 39.87285
Newton | Pennsylvania | United States | -75.8952 | 41.22258
Norristown | Pennsylvania | United States | -75.3399 | 40.1215
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Sellersville | Pennsylvania | United States | -75.3049 | 40.35399
Uniontown | Pennsylvania | United States | -79.71643 | 39.90008
Upland | Pennsylvania | United States | -75.38269 | 39.85261
Wynnewood | Pennsylvania | United States | -75.27074 | 40.00289
Wyomissing | Pennsylvania | United States | -75.96521 | 40.32954
Pawtucket | Rhode Island | United States | -71.38256 | 41.87871
Beaufort | South Carolina | United States | -80.66993 | 32.4317
Charleston | South Carolina | United States | -79.93275 | 32.77632
Greenville | South Carolina | United States | -82.39401 | 34.85262
Mt. Pleasant | South Carolina | United States | -79.86259 | 32.79407
Spartanburg | South Carolina | United States | -81.93205 | 34.94957
Summerville | South Carolina | United States | -80.17565 | 33.0185
West Columbia | South Carolina | United States | -81.07398 | 33.99349
Rapid City | South Dakota | United States | -103.23101 | 44.08054
Chattanooga | Tennessee | United States | -85.30968 | 35.04563
Germantown | Tennessee | United States | -89.81009 | 35.08676
Johnson City | Tennessee | United States | -82.35347 | 36.31344
Nashville | Tennessee | United States | -86.78444 | 36.16589
Nashville | Tennessee | United States | -86.78444 | 36.16589
Oak Ridge | Tennessee | United States | -84.26964 | 36.01036
Austin | Texas | United States | -97.74306 | 30.26715
Austin | Texas | United States | -97.74306 | 30.26715
Dallas | Texas | United States | -96.80667 | 32.78306
Fort Worth | Texas | United States | -97.32085 | 32.72541
Fort Worth | Texas | United States | -97.32085 | 32.72541
Houston | Texas | United States | -95.36327 | 29.76328
Killeen | Texas | United States | -97.7278 | 31.11712
Lubbock | Texas | United States | -101.85517 | 33.57786
McKinney | Texas | United States | -96.61527 | 33.19762
Plano | Texas | United States | -96.69889 | 33.01984
San Antonio | Texas | United States | -98.49363 | 29.42412
San Antonio | Texas | United States | -98.49363 | 29.42412
San Antonio | Texas | United States | -98.49363 | 29.42412
San Marcos | Texas | United States | -97.94139 | 29.88327
Tyler | Texas | United States | -95.30106 | 32.35126
Tyler | Texas | United States | -95.30106 | 32.35126
Arlington | Virginia | United States | -77.10428 | 38.88101
Charlottesville | Virginia | United States | -78.47668 | 38.02931
Chesapeake | Virginia | United States | -76.27494 | 36.81904
Danville | Virginia | United States | -79.39502 | 36.58597
Falls Church | Virginia | United States | -77.17109 | 38.88233
Fredericksburg | Virginia | United States | -77.46054 | 38.30318
Harrisonburg | Virginia | United States | -78.86892 | 38.44957
Newport News | Virginia | United States | -76.42975 | 36.98038
Norfolk | Virginia | United States | -76.28522 | 36.84681
Salem | Virginia | United States | -80.05476 | 37.29347
Winchester | Virginia | United States | -78.16333 | 39.18566
Bellevue | Washington | United States | -122.20068 | 47.61038
Bellingham | Washington | United States | -122.48822 | 48.75955
Burien | Washington | United States | -122.34679 | 47.47038
Olympia | Washington | United States | -122.90169 | 47.04491
Spokane | Washington | United States | -117.42908 | 47.65966
Tacoma | Washington | United States | -122.44429 | 47.25288
Wenatchee | Washington | United States | -120.31035 | 47.42346
Charleston | West Virginia | United States | -81.63262 | 38.34982
Clarksburg | West Virginia | United States | -80.34453 | 39.28065
Huntington | West Virginia | United States | -82.44515 | 38.41925
Elkhorn | Wisconsin | United States | -88.54454 | 42.67279
Green Bay | Wisconsin | United States | -88.01983 | 44.51916
Madison | Wisconsin | United States | -89.40123 | 43.07305
Madison | Wisconsin | United States | -89.40123 | 43.07305
Marshfield | Wisconsin | United States | -90.1718 | 44.66885
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Bahía Blanca | N/A | Argentina | -62.26545 | -38.7176
Capital Federal | N/A | Argentina | N/A | N/A
Capital Federal | N/A | Argentina | N/A | N/A
Cipolletti | N/A | Argentina | -67.99032 | -38.93392
Coronel Suárez | N/A | Argentina | -61.93294 | -37.45859
Córdoba | N/A | Argentina | -64.18853 | -31.40648
La Plata | N/A | Argentina | -57.95442 | -34.92126
Mar del Plata | N/A | Argentina | -57.5562 | -38.00042
Mar del Plata | N/A | Argentina | -57.5562 | -38.00042
Quilmes | N/A | Argentina | -58.25454 | -34.72065
Rosario | N/A | Argentina | -60.63932 | -32.94682
Salta | N/A | Argentina | -65.41999 | -24.80645
Santa Fe | N/A | Argentina | -60.70868 | -31.64881
Coffs Harbour | New South Wales | Australia | 153.11351 | -30.29626
Gosford | New South Wales | Australia | 151.34399 | -33.4244
Herston | Queensland | Australia | 153.01852 | -27.44453
Milton | Queensland | Australia | 153.00312 | -27.47039
Ashford | South Australia | Australia | 138.57457 | -34.94859
Launceston | Tasmania | Australia | 147.13467 | -41.43876
Box Hill | Victoria | Australia | 145.12545 | -37.81887
Geelong | Victoria | Australia | 144.36069 | -38.14711
Parkville | Victoria | Australia | 144.95 | -37.78333
Prahran | Victoria | Australia | 144.99318 | -37.85114
Graz | N/A | Austria | 15.45 | 47.06667
Linz | N/A | Austria | 14.28611 | 48.30639
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Wels | N/A | Austria | 14.03333 | 48.16667
Wiener Neustadt | N/A | Austria | 16.23196 | 47.80485
Aalst | N/A | Belgium | 4.0355 | 50.93604
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Brasschaat | N/A | Belgium | 4.49182 | 51.2912
Bruges | N/A | Belgium | 3.22424 | 51.20892
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Edegem | N/A | Belgium | 4.44504 | 51.15662
Genk | N/A | Belgium | 5.50082 | 50.965
Genk | N/A | Belgium | 5.50082 | 50.965
Ghent | N/A | Belgium | 3.71667 | 51.05
Gilly | N/A | Belgium | 4.4789 | 50.42449
Haine-St.-Paul | N/A | Belgium | N/A | N/A
Hasselt | N/A | Belgium | 5.33781 | 50.93106
Kortrijk | N/A | Belgium | 3.26487 | 50.82803
Leuven | N/A | Belgium | 4.70093 | 50.87959
Liège | N/A | Belgium | 5.56749 | 50.63373
Liège | N/A | Belgium | 5.56749 | 50.63373
Mol | N/A | Belgium | 5.11662 | 51.19188
Ostend | N/A | Belgium | 2.927 | 51.21551
Roeselare | N/A | Belgium | 3.12269 | 50.94653
Tienen | N/A | Belgium | 4.9378 | 50.80745
Turnhout | N/A | Belgium | 4.94471 | 51.32254
Belo Horizonte | N/A | Brazil | -43.93778 | -19.92083
Blumenau | N/A | Brazil | -49.06611 | -26.91944
Campinas | N/A | Brazil | -47.06083 | -22.90556
Curitiba | N/A | Brazil | -49.27306 | -25.42778
Curitiba | N/A | Brazil | -49.27306 | -25.42778
Curitiba | N/A | Brazil | -49.27306 | -25.42778
Goiânia | N/A | Brazil | -49.25389 | -16.67861
Marília | N/A | Brazil | -49.94583 | -22.21389
São José do Rio Preto | N/A | Brazil | -49.37944 | -20.81972
São José do Rio Preto | N/A | Brazil | -49.37944 | -20.81972
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
Uberaba | N/A | Brazil | -47.93194 | -19.74833
Pleven | N/A | Bulgaria | 24.61667 | 43.41667
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Stara Zagora | N/A | Bulgaria | 25.64194 | 42.43278
Varna | N/A | Bulgaria | 27.91667 | 43.21667
Calgary | Alberta | Canada | -114.08529 | 51.05011
Calgary | Alberta | Canada | -114.08529 | 51.05011
Coquitlam | British Columbia | Canada | -122.78217 | 49.2846
Coquitlam | British Columbia | Canada | -122.78217 | 49.2846
Kelowna | British Columbia | Canada | -119.48568 | 49.88307
Nanaimo | British Columbia | Canada | -123.94003 | 49.16638
New Westminster | British Columbia | Canada | -122.91092 | 49.20678
Victoria | British Columbia | Canada | -123.35155 | 48.4359
Portage la Prairie | Manitoba | Canada | -98.29263 | 49.97282
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Bay Roberts | Newfoundland and Labrador | Canada | -53.26478 | 47.59989
Antigonish | Nova Scotia | Canada | -61.99858 | 45.61685
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Ajax | Ontario | Canada | -79.03288 | 43.85012
Brampton | Ontario | Canada | -79.76633 | 43.68341
Burlington | Ontario | Canada | -79.83713 | 43.38621
Cambridge | Ontario | Canada | -80.31269 | 43.3601
Cambridge | Ontario | Canada | -80.31269 | 43.3601
Etobicoke | Ontario | Canada | -79.56985 | 43.64415
Greater Sudbury | Ontario | Canada | -80.99001 | 46.49
Grimsby | Ontario | Canada | -79.56631 | 43.20011
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Hamilton | Ontario | Canada | -79.84963 | 43.25011
Kitchener | Ontario | Canada | -80.5112 | 43.42537
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Mississauga | Ontario | Canada | -79.6583 | 43.5789
Newmarket | Ontario | Canada | -79.46631 | 44.05011
Oshawa | Ontario | Canada | -78.84957 | 43.90012
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Scarborough Village | Ontario | Canada | -79.22124 | 43.73899
Thunder Bay | Ontario | Canada | -89.25018 | 48.38202
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Waterloo | Ontario | Canada | -80.51639 | 43.4668
Windsor | Ontario | Canada | -83.01654 | 42.30008
Longueuil | Quebec | Canada | -73.46818 | 45.5152
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Québec | Quebec | Canada | -71.21454 | 46.81228
Saint George-de-Beauce | Quebec | Canada | N/A | N/A
Saint-Charles-Borromée | Quebec | Canada | -73.46586 | 46.05007
Saint-Hyacinthe | Quebec | Canada | -72.95699 | 45.63076
Saint-Jérôme | Quebec | Canada | -74.00365 | 45.78036
Ste-Foy | Quebec | Canada | N/A | N/A
Terrebonne (Lachenaie) | Quebec | Canada | -73.64732 | 45.70004
Saskatoon | Saskatchewan | Canada | -106.66892 | 52.13238
Saskatoon | Saskatchewan | Canada | -106.66892 | 52.13238
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Hangzhou | N/A | China | 120.16142 | 30.29365
Harbin | N/A | China | 126.65 | 45.75
Qingdao | N/A | China | 120.38042 | 36.06488
Shanghai | N/A | China | 121.45806 | 31.22222
Shanghai | N/A | China | 121.45806 | 31.22222
Shenyang | N/A | China | 123.43278 | 41.79222
Shijiazhuang | N/A | China | 114.47861 | 38.04139
Bogotá | N/A | Colombia | -74.08175 | 4.60971
Bogotá | N/A | Colombia | -74.08175 | 4.60971
Bogotá | N/A | Colombia | -74.08175 | 4.60971
Brno | N/A | Czechia | 16.60796 | 49.19522
Brno | N/A | Czechia | 16.60796 | 49.19522
Ostrava | N/A | Czechia | 18.28204 | 49.83465
Pardubice | N/A | Czechia | 15.77659 | 50.04075
Plzen-Bory | N/A | Czechia | N/A | N/A
Pragha 9 | N/A | Czechia | N/A | N/A
Prague | N/A | Czechia | 14.42076 | 50.08804
Prague | N/A | Czechia | 14.42076 | 50.08804
Příbram | N/A | Czechia | 14.01043 | 49.68988
Ústí nad Orlicí | N/A | Czechia | 16.39361 | 49.97387
Aalborg | N/A | Denmark | 9.9187 | 57.048
Aarhus C | N/A | Denmark | 10.21231 | 56.16558
Elsinore | N/A | Denmark | 12.6136 | 56.03606
Frederikssund | N/A | Denmark | 12.06896 | 55.83956
Herlev | N/A | Denmark | 12.43998 | 55.72366
Horsens | N/A | Denmark | 9.85034 | 55.86066
Hvidovre | N/A | Denmark | 12.47708 | 55.64297
Køge | N/A | Denmark | 12.18214 | 55.45802
Odense | N/A | Denmark | 10.38831 | 55.39594
Roskilde | N/A | Denmark | 12.08035 | 55.64152
Svendborg | N/A | Denmark | 10.60677 | 55.05982
Espoo | N/A | Finland | 24.6522 | 60.2052
HUS | N/A | Finland | N/A | N/A
Jyväskylä | N/A | Finland | 25.72088 | 62.24147
Kuopio | N/A | Finland | 27.67703 | 62.89238
Lappeenranta | N/A | Finland | 28.18871 | 61.05871
OYS | N/A | Finland | N/A | N/A
Pori | N/A | Finland | 21.78333 | 61.48333
Tampere | N/A | Finland | 23.78712 | 61.49911
Turku | N/A | Finland | 22.26869 | 60.45148
Abbeville | N/A | France | 1.83547 | 50.10521
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Angers | N/A | France | -0.55202 | 47.47156
Cholet | N/A | France | -0.87974 | 47.05893
Gap | N/A | France | 6.07868 | 44.55858
Grenoble | N/A | France | 5.71479 | 45.17869
Joué Les Tours | N/A | France | N/A | N/A
Joué Les Tours | N/A | France | N/A | N/A
Joué Les Tours | N/A | France | N/A | N/A
Joué Les Tours | N/A | France | N/A | N/A
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Joué-lès-Tours | N/A | France | 0.66513 | 47.34907
Langres | N/A | France | 5.33308 | 47.86263
Langres | N/A | France | 5.33308 | 47.86263
Paris | N/A | France | 2.3488 | 48.85341
Toulouse | N/A | France | 1.44367 | 43.60426
Tourcoing | N/A | France | 3.16117 | 50.72391
Valenciennes | N/A | France | 3.52506 | 50.35909
Valenciennes | N/A | France | 3.52506 | 50.35909
Valenciennes | N/A | France | 3.52506 | 50.35909
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Bochum | N/A | Germany | 7.21648 | 51.48165
Coburg | N/A | Germany | 10.96384 | 50.25937
Cologne | N/A | Germany | 6.95 | 50.93333
Dachau | N/A | Germany | 11.43402 | 48.26
Dortmund | N/A | Germany | 7.466 | 51.51494
Duisburg | N/A | Germany | 6.76516 | 51.43247
Erlangen | N/A | Germany | 11.00783 | 49.59099
Eschweiler | N/A | Germany | 6.27184 | 50.81854
Essen | N/A | Germany | 7.01228 | 51.45657
Frankfurt am Main | N/A | Germany | 8.68417 | 50.11552
Heidelberg | N/A | Germany | 8.69079 | 49.40768
Kassel | N/A | Germany | 9.5 | 51.31667
Lahr | N/A | Germany | 7.86886 | 48.34042
Limburg | N/A | Germany | 12.18221 | 48.03138
Mainz | N/A | Germany | 8.2791 | 49.98419
Mannheim | N/A | Germany | 8.46694 | 49.4891
Mannheim | N/A | Germany | 8.46694 | 49.4891
Mannheim | N/A | Germany | 8.46694 | 49.4891
München | N/A | Germany | 13.31243 | 51.60698
München | N/A | Germany | 13.31243 | 51.60698
Papenburg | N/A | Germany | 7.40444 | 53.07738
Suhl | N/A | Germany | 10.69401 | 50.60911
Witten | N/A | Germany | 7.35258 | 51.44362
Wuppertal | N/A | Germany | 7.14816 | 51.25627
Alexandroupoli | N/A | Greece | 25.87644 | 40.84995
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Kalamaria-Thessaloniki | N/A | Greece | N/A | N/A
Larissa | N/A | Greece | 22.41761 | 39.63689
Larissa | N/A | Greece | 22.41761 | 39.63689
Livadeia | N/A | Greece | 22.87665 | 38.43616
Thebes | N/A | Greece | 23.31889 | 38.325
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Trikala | N/A | Greece | 21.76837 | 39.55493
Voula - Athens | N/A | Greece | N/A | N/A
Hong Kong | N/A | Hong Kong | 114.17469 | 22.27832
Hong Kong | N/A | Hong Kong | 114.17469 | 22.27832
Kowloon | N/A | Hong Kong | 114.18333 | 22.31667
Kowloon | N/A | Hong Kong | 114.18333 | 22.31667
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Gyöngyös | N/A | Hungary | 19.928 | 47.78257
Komárom | N/A | Hungary | 18.11913 | 47.74318
Pécs | N/A | Hungary | 18.23083 | 46.0725
Veszprém | N/A | Hungary | 17.91149 | 47.09327
Ahmedabad | N/A | India | 72.58727 | 23.02579
Ahmedabad | N/A | India | 72.58727 | 23.02579
Bangalore | N/A | India | 77.59369 | 12.97194
Bangalore | N/A | India | 77.59369 | 12.97194
Bikaner | N/A | India | 73.31495 | 28.01762
Chennai | N/A | India | 80.27847 | 13.08784
Coimbatore | N/A | India | 76.96612 | 11.00555
Hyderabad | N/A | India | 78.45636 | 17.38405
Indore | N/A | India | 75.8333 | 22.71792
Jaipur | N/A | India | 75.78781 | 26.91962
Jaipur | N/A | India | 75.78781 | 26.91962
Kerala | N/A | India | N/A | N/A
Kottayam | N/A | India | 76.52132 | 9.58692
Lucknow | N/A | India | 80.92313 | 26.83928
Ludhiana | N/A | India | 75.85379 | 30.91204
Mumbai | N/A | India | 72.88261 | 19.07283
Mysore | N/A | India | 76.63925 | 12.29791
Nagpur | N/A | India | 79.08491 | 21.14631
New Delhi | N/A | India | 77.2148 | 28.62137
Pune | N/A | India | 73.85535 | 18.51957
Afula | N/A | Israel | 35.2892 | 32.60907
Afula | N/A | Israel | 35.2892 | 32.60907
Ashkelon | N/A | Israel | 34.57149 | 31.66926
Beersheba | N/A | Israel | 34.7913 | 31.25181
Giv‘atayim | N/A | Israel | 34.81253 | 32.07225
Hadera | N/A | Israel | 34.9039 | 32.44192
Haifa | N/A | Israel | 34.99928 | 32.81303
Haifa | N/A | Israel | 34.99928 | 32.81303
Haifa | N/A | Israel | 34.99928 | 32.81303
Haifa | N/A | Israel | 34.99928 | 32.81303
Haifa | N/A | Israel | 34.99928 | 32.81303
Holon | N/A | Israel | 34.77918 | 32.01034
Jerusalem | N/A | Israel | 35.21633 | 31.76904
Jerusalem | N/A | Israel | 35.21633 | 31.76904
Jerusalem | N/A | Israel | 35.21633 | 31.76904
Jerusalem | N/A | Israel | 35.21633 | 31.76904
Kfar Saba | N/A | Israel | 34.90694 | 32.175
Nazareth | N/A | Israel | 35.29719 | 32.70087
Petah Tikva | N/A | Israel | 34.88747 | 32.08707
Ramat Gan | N/A | Israel | 34.81065 | 32.08227
Ramat Gan | N/A | Israel | 34.81065 | 32.08227
Ramat Gan | N/A | Israel | 34.81065 | 32.08227
Rehovot | N/A | Israel | 34.81199 | 31.89421
Safed | N/A | Israel | 35.496 | 32.96465
Tel Aviv | N/A | Israel | 34.78057 | 32.08088
Tel Aviv | N/A | Israel | 34.78057 | 32.08088
Tel Aviv | N/A | Israel | 34.78057 | 32.08088
Tel Aviv | N/A | Israel | 34.78057 | 32.08088
Tel Aviv | N/A | Israel | 34.78057 | 32.08088
Tel Litwinsky | N/A | Israel | 34.84588 | 32.05096
Tel Litwinsky | N/A | Israel | 34.84588 | 32.05096
Ẕerifin | N/A | Israel | 34.84852 | 31.95731
Arezzo | N/A | Italy | 11.88068 | 43.46276
Ascoli Piceno | N/A | Italy | 13.57395 | 42.85351
Bentivoglio (BO) | N/A | Italy | 11.41737 | 44.6369
Bologna | N/A | Italy | 11.33875 | 44.49381
Castelnuovo Garfagnana | N/A | Italy | N/A | N/A
Chieti | N/A | Italy | 14.16494 | 42.34827
Colleferro | N/A | Italy | 13.00481 | 41.72722
Cremona | N/A | Italy | 10.02129 | 45.13325
Eboli | N/A | Italy | 15.05693 | 40.61747
Isernia | N/A | Italy | 14.23399 | 41.59603
Legnago | N/A | Italy | 11.30227 | 45.19365
Mantova | N/A | Italy | 10.79784 | 45.16031
Perugia SAN Sisto | N/A | Italy | N/A | N/A
Roma | N/A | Italy | 11.10642 | 44.99364
San Bonifacio | N/A | Italy | 11.27352 | 45.39595
San Daniele del Friuli | N/A | Italy | 13.00726 | 46.15714
Sassari | N/A | Italy | 8.55552 | 40.72586
Sassari | N/A | Italy | 8.55552 | 40.72586
Abeno-ku, Osaka, Osaka | N/A | Japan | N/A | N/A
Aki-gun, Hiroshima | N/A | Japan | 132.45 | 34.4
Aoba-ku, Sendai, Miyagi | N/A | Japan | N/A | N/A
Chuo-ku, Fukuoka, Fukuoka | N/A | Japan | N/A | N/A
Chuo-ku, Fukuoka, Fukuoka | N/A | Japan | N/A | N/A
Chuo-ku, Kobe, Hyogo | N/A | Japan | N/A | N/A
Chuo-ku, Osaka, Osaka | N/A | Japan | N/A | N/A
Fujioka-shi , Gunma-ken | N/A | Japan | N/A | N/A
Fukushima-shi,Fukushima-ken | N/A | Japan | 140.46667 | 37.75
Higashimatsushimashi, Miyagi-ken | N/A | Japan | N/A | N/A
Himeji, Hyogo | N/A | Japan | N/A | N/A
Iida, Nagano | N/A | Japan | N/A | N/A
Isesaki-shi,Gunma | N/A | Japan | N/A | N/A
Iwakuni, Yamaguchi | N/A | Japan | N/A | N/A
Izumi-ku, Sendai, Miyagi | N/A | Japan | N/A | N/A
Kamigyo-ku, Kyoto | N/A | Japan | N/A | N/A
Kawachinagano, Osaka | N/A | Japan | N/A | N/A
Kita-ku, Osaka, Osaka | N/A | Japan | N/A | N/A
Kita-ku, Sakai, Osaka | N/A | Japan | N/A | N/A
Komatsu-shi,Ishikawa -ken | N/A | Japan | N/A | N/A
Kyoto-shi,Kyoto | N/A | Japan | N/A | N/A
Matsumoto, Nagano | N/A | Japan | N/A | N/A
Minami-ku, Fukuoka, Fukuoka | N/A | Japan | N/A | N/A
Minato, Tokyo | N/A | Japan | N/A | N/A
Minato-ku, Nagoya, Aichi | N/A | Japan | N/A | N/A
Minato-ku, Nagoya, Aichi | N/A | Japan | N/A | N/A
Narashino, Chiba | N/A | Japan | N/A | N/A
Nishinomiya-shi,Hyogo | N/A | Japan | 144.43333 | 43.36667
Okayama, Okayama | N/A | Japan | N/A | N/A
Oota, Tokyo | N/A | Japan | N/A | N/A
Otaru, Hokkaido | N/A | Japan | 141.00222 | 43.18944
Sagamihara, Kanagawa-ken | N/A | Japan | 139.24167 | 35.56707
Sapporo-shi,Hokkai-do | N/A | Japan | 141.35 | 43.06667
Shibuya, Tokyo | N/A | Japan | N/A | N/A
Shinjuku, Tokyo | N/A | Japan | N/A | N/A
Shiroishi-ku, Sapporo, Hokkaido | N/A | Japan | 141.35 | 43.06667
Shiroishi-ku, Sapporo, Hokkaido | N/A | Japan | 141.35 | 43.06667
Suita, Osaka | N/A | Japan | N/A | N/A
Suita-shi, Osaka | N/A | Japan | 135.50107 | 34.69379
Suita-shi, Osaka | N/A | Japan | 135.50107 | 34.69379
Sumiyoshi-ku, Osaka, Osaka | N/A | Japan | N/A | N/A
Takatsuki-shi,Osaka | N/A | Japan | 135.50107 | 34.69379
Tokorozawa, Saitama | N/A | Japan | N/A | N/A
Totsuka-ku, Yokohama, Kanagawa | N/A | Japan | N/A | N/A
Tsuchiura, Ibaragi | N/A | Japan | N/A | N/A
Ueda, Nagano | N/A | Japan | N/A | N/A
Wakayama, Wakayama | N/A | Japan | N/A | N/A
Yanagawa, Fukuoka | N/A | Japan | N/A | N/A
Yao, Osaka | N/A | Japan | N/A | N/A
George Town | N/A | Malaysia | 100.33543 | 5.41123
George Town | N/A | Malaysia | 100.33543 | 5.41123
Kajang,Selangor | N/A | Malaysia | N/A | N/A
Kuala Lumpur | N/A | Malaysia | 101.68653 | 3.1412
Kuala Lumpur | N/A | Malaysia | 101.68653 | 3.1412
Kuala Lumpur | N/A | Malaysia | 101.68653 | 3.1412
Kuching | N/A | Malaysia | 110.33333 | 1.55
Durango | N/A | Mexico | -104.65756 | 24.02032
Guadalajara | N/A | Mexico | -103.34749 | 20.67738
Guadalajara | N/A | Mexico | -103.34749 | 20.67738
Mexico | N/A | Mexico | -98.43784 | 18.88011
Mexico | N/A | Mexico | -98.43784 | 18.88011
México | N/A | Mexico | -103.57339 | 22.76088
San Luis Potosí City | N/A | Mexico | -100.97135 | 22.15234
San Luis Potosí City | N/A | Mexico | -100.97135 | 22.15234
's-Hertogenbosch | N/A | Netherlands | 5.30417 | 51.69917
Almelo | N/A | Netherlands | 6.6625 | 52.35667
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Apeldoorn | N/A | Netherlands | 5.96944 | 52.21
Breda | N/A | Netherlands | 4.77596 | 51.58656
Den Helder | N/A | Netherlands | 4.75933 | 52.95988
Deventer | N/A | Netherlands | 6.16389 | 52.255
Dirksland | N/A | Netherlands | 4.1 | 51.74917
Dordrecht | N/A | Netherlands | 4.67361 | 51.81
Ede | N/A | Netherlands | 5.65833 | 52.03333
Eindhoven | N/A | Netherlands | 5.47778 | 51.44083
Enschede | N/A | Netherlands | 6.89583 | 52.21833
Goes | N/A | Netherlands | 3.88889 | 51.50417
Gorinchem | N/A | Netherlands | 4.97243 | 51.83652
Groningen | N/A | Netherlands | 6.56667 | 53.21917
Groningen | N/A | Netherlands | 6.56667 | 53.21917
Heerlen | N/A | Netherlands | 5.98154 | 50.88365
Hengelo | N/A | Netherlands | 6.79306 | 52.26583
Hilversum | N/A | Netherlands | 5.17639 | 52.22333
Hoorn | N/A | Netherlands | 5.05972 | 52.6425
Maastricht | N/A | Netherlands | 5.68889 | 50.84833
Meppel | N/A | Netherlands | 6.19444 | 52.69583
Rotterdam | N/A | Netherlands | 4.47917 | 51.9225
Sneek | N/A | Netherlands | 5.6589 | 53.03297
Spiijkenisse | N/A | Netherlands | N/A | N/A
Terneuzen | N/A | Netherlands | 3.82778 | 51.33583
Tiel | N/A | Netherlands | 5.42917 | 51.88667
Tilburg | N/A | Netherlands | 5.0913 | 51.55551
Veldhoven | N/A | Netherlands | 5.40278 | 51.41833
Velp | N/A | Netherlands | 5.97361 | 51.995
Venlo | N/A | Netherlands | 6.16806 | 51.37
Gjøvik | N/A | Norway | 10.69155 | 60.79574
Moss | N/A | Norway | 10.65771 | 59.43403
Nordbyhagen | N/A | Norway | N/A | N/A
Oslo | N/A | Norway | 10.74609 | 59.91273
Oslo | N/A | Norway | 10.74609 | 59.91273
Oslo | N/A | Norway | 10.74609 | 59.91273
Rud | N/A | Norway | 11.63333 | 60.43333
Bella Vista | N/A | Peru | -71.36056 | -16.56694
Jesús María | N/A | Peru | -72.66667 | -13.55
San Isidro | N/A | Peru | -77.04258 | -12.09655
San Martín de Porres | N/A | Peru | -74.56901 | -8.39936
Urbanización Sto Tomas de San Borja | N/A | Peru | N/A | N/A
Manila | N/A | Philippines | 120.9822 | 14.6042
Manila | N/A | Philippines | 120.9822 | 14.6042
Pasig | N/A | Philippines | 121.0614 | 14.58691
Quezon City | N/A | Philippines | 121.0509 | 14.6488
Quezon City | N/A | Philippines | 121.0509 | 14.6488
Gdynia | N/A | Poland | 18.53188 | 54.51889
Gdynia | N/A | Poland | 18.53188 | 54.51889
Gdynia Redlowo | N/A | Poland | N/A | N/A
Katowice | N/A | Poland | 19.02754 | 50.25841
Krakow | N/A | Poland | 19.93658 | 50.06143
Krakow | N/A | Poland | 19.93658 | 50.06143
Puławy | N/A | Poland | 21.96939 | 51.41655
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Zabrze | N/A | Poland | 18.78576 | 50.32492
Amadora | N/A | Portugal | -9.23083 | 38.75382
Carnaxide | N/A | Portugal | -9.24671 | 38.72706
Coimbra | N/A | Portugal | -8.41955 | 40.20564
Coimbra | N/A | Portugal | -8.41955 | 40.20564
Covilha | N/A | Portugal | -7.50504 | 40.28106
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Porto | N/A | Portugal | -8.61099 | 41.14961
Setúbal | N/A | Portugal | -8.8882 | 38.5244
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Cluj-Napoca | N/A | Romania | 23.6 | 46.76667
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Singapore | N/A | Singapore | 103.85007 | 1.28967
Singapore | N/A | Singapore | 103.85007 | 1.28967
Banská Bystrica | N/A | Slovakia | 19.15349 | 48.73946
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Košice | N/A | Slovakia | 21.25808 | 48.71395
Košice | N/A | Slovakia | 21.25808 | 48.71395
Žilina | N/A | Slovakia | 18.73941 | 49.22315
Bloemfontein | N/A | South Africa | 26.214 | -29.12107
Boksburg | N/A | South Africa | 28.25958 | -26.21197
Cape Town | N/A | South Africa | 18.42322 | -33.92584
Johannesburg | N/A | South Africa | 28.04363 | -26.20227
Johannesburg | N/A | South Africa | 28.04363 | -26.20227
Johannesburg | N/A | South Africa | 28.04363 | -26.20227
Pretoria | N/A | South Africa | 28.18783 | -25.74486
Randburg | N/A | South Africa | 28.00123 | -26.0941
Somerset West | N/A | South Africa | 18.82113 | -34.08401
Busan | N/A | South Korea | 129.03004 | 35.10168
Chungchungnam-Do | N/A | South Korea | N/A | N/A
Daegu | N/A | South Korea | 128.59111 | 35.87028
Daegu | N/A | South Korea | 128.59111 | 35.87028
Gwangju | N/A | South Korea | 126.91556 | 35.15472
Incheon | N/A | South Korea | 126.70515 | 37.45646
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Barcelona | N/A | Spain | 2.15899 | 41.38879
Cadiz | N/A | Spain | -6.2891 | 36.52672
Fuenlabrada (Madrid) | N/A | Spain | -3.79415 | 40.28419
Leganés, Madrid | N/A | Spain | N/A | N/A
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid | N/A | Spain | -3.70256 | 40.4165
Madrid-San Lorenzo Del Escorial | N/A | Spain | N/A | N/A
Móstoles (Madrid) | N/A | Spain | -3.86496 | 40.32234
Sabadell | N/A | Spain | 2.10942 | 41.54329
Göteboerg | N/A | Sweden | N/A | N/A
Jönköping | N/A | Sweden | 14.15618 | 57.78145
Linköping | N/A | Sweden | 15.62157 | 58.41086
Malmo | N/A | Sweden | 13.00073 | 55.60587
Nässjö | N/A | Sweden | 14.69676 | 57.65307
Norrköping | N/A | Sweden | 16.1826 | 58.59419
Örebro | N/A | Sweden | 15.2066 | 59.27412
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Umeå | N/A | Sweden | 20.25972 | 63.82842
Uppsala | N/A | Sweden | 17.63889 | 59.85882
Uppsala | N/A | Sweden | 17.63889 | 59.85882
Västerås | N/A | Sweden | 16.55276 | 59.61617
Basel | N/A | Switzerland | 7.57327 | 47.55839
Bellinzona | N/A | Switzerland | 9.01703 | 46.19278
Bern | N/A | Switzerland | 7.44744 | 46.94809
Lugano | N/A | Switzerland | 8.96004 | 46.01008
Changhua County | N/A | Taiwan | N/A | N/A
Hualien City | N/A | Taiwan | 121.60444 | 23.97694
Kaohsiung City | N/A | Taiwan | 120.31333 | 22.61626
Taichung | N/A | Taiwan | 120.6839 | 24.1469
Tainan City | N/A | Taiwan | 120.21333 | 22.99083
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taoyuan District | N/A | Taiwan | 121.3187 | 24.9896
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Chiang Mai | N/A | Thailand | 98.98468 | 18.79038
Khon Kaen | N/A | Thailand | 102.833 | 16.44671
Muang Nakhonratchasima | N/A | Thailand | N/A | N/A
Adana | N/A | Turkey (Türkiye) | 35.32531 | 36.98615
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Izmir | N/A | Turkey (Türkiye) | 27.13838 | 38.41273
Dnyepropetrovsk | N/A | Ukraine | N/A | N/A
Kharkiv | N/A | Ukraine | 36.25475 | 49.98177
Kharkiv | N/A | Ukraine | 36.25475 | 49.98177
Kharkiv | N/A | Ukraine | 36.25475 | 49.98177
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Kiev | N/A | Ukraine | 30.5238 | 50.45466
Lviv | N/A | Ukraine | 24.02324 | 49.83826
Birmingham | N/A | United Kingdom | -1.89983 | 52.48142
Chertsey | N/A | United Kingdom | -0.50782 | 51.38812
Glasgow | N/A | United Kingdom | -4.25763 | 55.86515
Harrow | N/A | United Kingdom | -0.33208 | 51.57835
Hull | N/A | United Kingdom | -0.33525 | 53.7446
Kirkcaldy, Fife | N/A | United Kingdom | -3.15999 | 56.11683
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
Londonderry | N/A | United Kingdom | -7.30934 | 54.9981
Newcastle upon Tyne | N/A | United Kingdom | -1.61396 | 54.97328
Newport | N/A | United Kingdom | -2.99835 | 51.58774
Northampton | N/A | United Kingdom | -0.88333 | 52.25
Portadown, County Atrim | N/A | United Kingdom | -6.44434 | 54.42302
Romford, Essex | N/A | United Kingdom | 0.18582 | 51.57515
Stoke-on-Trent | N/A | United Kingdom | -2.18538 | 53.00415
York | N/A | United Kingdom | -1.08271 | 53.95763 | 18,040 | 22 | 0.00122 | 1 | NCT00262600 | 1COMPLETED | 2009-04-01 | 2005-12-01 | Boehringer Ingelheim | 4INDUSTRY | false | false | false | null | 0 | 7 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0.000806 | |
[
5
] | 415 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | null | This 2-arm study will compare the efficacy and safety of treatment with Pegasys (180 µg weekly) plus Copegus (800 mg daily) and Pegasys (180 µg weekly) plus Copegus (1000-1200 mg daily) in interferon-naive patients with CHC genotype 1 co-infected with HIV-1. Treatment will be administered for 48 weeks, and this will be followed by 24 treatment-free weeks. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals. | null | Hepatitis C, Chronic | null | 2 | arm 1: None arm 2: None | [
0,
1
] | 3 | [
0,
0,
0
] | intervention 1: 180 µg subcutaneously weekly for 48 weeks intervention 2: 800 mg orally daily for 48 weeks intervention 3: 1000 mg or 1200 mg (based on patient weight of \< 75 kg or ≥ 75 kg, respectively) orally daily for 48 weeks | intervention 1: Peginterferon alfa-2a intervention 2: Ribavirin intervention 3: Ribavirin | 0 | null | 409 | 1 | 0.002445 | 1 | NCT00353418 | 1COMPLETED | 2009-04-01 | 2006-06-01 | Hoffmann-La Roche | 4INDUSTRY | false | false | false | null | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000432 | |
[
4
] | 585 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | The purpose of this randomized, double blind, double dummy, multicenter study was to evaluate the efficacy of risperidone long-acting injectable (LAI) monotherapy in comparison with placebo in the prevention of a mood episode in treatment of patients with bipolar I disorder. Oral olanzapine was used to assess the validity of the study design. The primary objective of this study is to evaluate the efficacy of risperidone LAI versus placebo in the prevention of a mood episode (recurrence event) in patients with bipolar I disorder after a 12-week (3 month) stabilization period on risperidone LAI, as measured by the time to recurrence of any mood episode. Risperidone LAI has been approved by the FDA in the USA for the treatment of patients with schizophrenia and for the prevention of mood recurrences in bipolar I disorder, as monotherapy or add-on treatment. It is approved at EMEA and other European and non-European health authorities for the treatment of patients with schizophrenia, too. | This is a randomized, double-blind, double-dummy multicenter study with 3 parallel arms (risperidone long-acting injectable (LAI), placebo, and olanzapine) to evaluate the efficacy and safety of risperidone LAI versus placebo in the prevention of a mood episode (recurrence event). The primary objective of this study is to evaluate the efficacy of risperidone LAI monotherapy versus placebo in the prevention of a mood episode (recurrence event) in patients with bipolar I disorder after a 12-week (3 month) stabilization period on risperidone LAI, as measured by the time to recurrence of any mood episode. This study includes 3 periods - the screening period (Period I, lasting up to 2 weeks); the open-label treatment period (Period II, lasting 12 weeks); and the double-blind treatment period (Period III, lasting up to 18 months and at least 9 months). In the open -label treatment period (Period II) treatment with risperidone LAI will be started with injection of a recommended dose of 25 mg every 14 days in patients entering Period II. If judged clinically appropriate, patients may start with 37.5 mg every 14 days. Dosage can only be increased (up to a maximum dose of 50 mg every 14 days) if the Clinical Global Impression - Severity (CGI-S) score has increased by =\> 1 over 2 consecutive assessments at least 2 weeks apart and if there is symptom exacerbation that cannot be treated adequately with short-term (14 days) benzodiazepine medication. If an increase in risperidone LAI dosage is necessary, oral risperidone (1 to 2 mg/day) needs to be added for 3 weeks after the first injection of the higher dosage. Washout of all psychotropics other than risperidone long acting must be completed by the end of the first week. Non-acute patients on an antipsychotic or mood stabilizer for at least 4 weeks will continue their previous treatment for the first 3 weeks. No changes will be made in the regimens of non-acute patients receiving an antipsychotic or mood stabilizer unless there is concern about efficacy or safety.Patients experiencing an acute manic or mixed episode will additionally be treated with oral risperidone at whole-milligram dosages between 1 and 6 mg/day as needed to treat the symptoms of the acute episode for the first 3 weeks, in order to cover the 3 weeks lag period of Risperidone long acting. Patients experiencing an acute episode who do not respond to treatment within 4 weeks will be discontinued from the study. Patients who do not show a response (acute patients at baseline) or do not maintain the efficacy (non-acute patients at baseline and acute patients after initial response) during the 12-week (3 month) open-label risperidone LAI stabilization period (Period II), will be discontinued from the study as soon as any one of the following criteria is met: The patient meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, text revised (DSM-IV-TR) criteria for a hypomanic, manic, mixed, or depressive episode; the patient needs treatment intervention with any mood stabilizer, antipsychotic medication (other than study drug), benzodiazepine (beyond the dosage allowed), or antidepressant medication; the patient requires hospitalization for any bipolar mood episode; the patient either has a Young Mania Rating Scale (YMRS) score \>12 in combination with CGI-S score =\>4 or a Montgomery-Åsberg Depression Rating Scale (MADRS) score \>12 in combination with a CGI-S score =\>4. (If either of these criteria is fulfilled at an assessment but if the investigator assumes that this is only a temporary state that requires no action, the investigator is allowed to postpone the decision about maintenance or response by a maximum of 4 days. If after 4 days, the criteria are still met, the patient must be withdrawn from Period II.) Patients who show initial and maintained response (acute patients at baseline) or who maintain the efficacy (non-acute patients at baseline) during the 12-week (3-month) open-label risperidone LAI stabilization period (Period II), will be eligible for entering the double-blind treatment period (Period III). Patients who enter Period III will be randomized to receive intramuscular injections of risperidone LAI every 14 days (at the dosage achieved at the end of Period II) and oral placebo daily, or placebo injections every 14 days and oral placebo daily, or placebo injections every 14 days and oral olanzapine 10 mg/day. No supplementation with oral risperidone and no dosage titration will be allowed during this period of the study. Using the double-dummy design, all patients will receive an intramuscular injection every 14 days and will take oral medication every day. Patients who present with a recurrence during Period III, will be considered as meeting the end point of the study. Patients will remain in the double-blind treatment period until they meet recurrence criteria, until they withdraw consent, or are lost to follow-up, until the last patient completed at least 9 months without a mood episode in Period III, or until the study ends. The study will end when 158 patients have presented with a mood episode in Period III, or if the study is terminated based on the decision of the sponsor. Approximately 860 patients meeting the inclusion and exclusion criteria will be enrolled in this study, with the goal of observing at least 158 recurrence events in Period III. Safety evaluations will include adverse events, clinical laboratory tests - including blood glucose/lipid profile (fasting), prolactin, TSH, and urinalysis - vital signs (pulse and blood pressure) and ECG, physical examination, body weight and height, the Extrapyramidal Symptom Rating Scale, pregnancy testing, and urine drug screen. The patients will receive risperidone LAI (25, 37.5 or 50 mg (period II)) every 14 days during the 12 week long open-label period (Period II). Patients who enter the double-blind period (Period III) will be randomized to receive intramuscular injections of risperidone LAI every 14 days and oral placebo daily, or placebo injections every 14 days and oral placebo daily, or placebo injections every 14 days and oral olanzapine 10 mg/day. | Bipolar Disorder | Bipolar I Disorder Intramuscular injection prevention of mood episodes long acting injectable risperidone | null | 3 | arm 1: Risperidone Long Acting Injectable (LAI) Intramuscular injections of risperidone LAI (25 37.5 or 50 mg) every 2 weeks and oral placebo daily arm 2: Placebo Intramuscular injections of placebo every 2 weeks and oral placebo daily arm 3: Olanzapine Intramuscular injections of placebo every 2 weeks and oral olanzapine 10 mg daily | [
0,
2,
1
] | 3 | [
0,
0,
0
] | intervention 1: Intramuscular injections of placebo every 2 weeks and oral olanzapine 10 mg daily intervention 2: Intramuscular injections of placebo every 2 weeks and oral placebo daily intervention 3: Intramuscular injections of risperidone LAI (25, 37.5, or 50 mg) every 2 weeks and oral placebo daily | intervention 1: Olanzapine intervention 2: Placebo intervention 3: Risperidone Long Acting Injectable (LAI) | 63 | Baoding | N/A | China | 115.46246 | 38.87288
Beijing | N/A | China | 116.39723 | 39.9075
Guangzhou | N/A | China | 113.25 | 23.11667
Nanjing | N/A | China | 118.77778 | 32.06167
Shanghai | N/A | China | 121.45806 | 31.22222
Suozhou | N/A | China | N/A | N/A
Wuhan | N/A | China | 114.26667 | 30.58333
Barranquilla Atlantico | N/A | Colombia | N/A | N/A
Bello Antioquia | N/A | Colombia | N/A | N/A
Bogotá | N/A | Colombia | -74.08175 | 4.60971
Bogotá S/N | N/A | Colombia | N/A | N/A
Medellin Antioquia | N/A | Colombia | N/A | N/A
Pereira Risaralda | N/A | Colombia | N/A | N/A
Freiburg im Breisgau | N/A | Germany | 7.85222 | 47.9959
Hildesheim | N/A | Germany | 9.95112 | 52.15077
Oranienburg | N/A | Germany | 13.24197 | 52.75577
Athens | N/A | Greece | 23.72784 | 37.98376
Ahmedabad | N/A | India | 72.58727 | 23.02579
Bangalore | N/A | India | 77.59369 | 12.97194
Chennai | N/A | India | 80.27847 | 13.08784
Hyderabad | N/A | India | 78.45636 | 17.38405
Ludhiana | N/A | India | 75.85379 | 30.91204
Mangalore | N/A | India | 74.85603 | 12.91723
Mumbai | N/A | India | 72.88261 | 19.07283
New Delhi | N/A | India | 77.2148 | 28.62137
Pune | N/A | India | 73.85535 | 18.51957
Varanasi | N/A | India | 83.01041 | 25.31668
Jakarta | N/A | Indonesia | 106.84513 | -6.21462
Amman | N/A | Jordan | 35.94503 | 31.95522
Beirut | N/A | Lebanon | 35.50157 | 33.89332
Johor Bahru | N/A | Malaysia | 103.7578 | 1.4655
Kuala Lumpur | N/A | Malaysia | 101.68653 | 3.1412
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mérida | N/A | Mexico | -89.62318 | 20.967
Monterrey | N/A | Mexico | -100.31721 | 25.68435
Puebla City | N/A | Mexico | -98.20723 | 19.04778
Tabasco | N/A | Mexico | -102.91108 | 21.86315
Tampico | N/A | Mexico | -97.87777 | 22.28519
Zapopan | N/A | Mexico | -103.38742 | 20.72111
Lima | N/A | Peru | -77.02824 | -12.04318
Lima Lima | N/A | Peru | -75.68858 | -11.23494
Iloilo City | N/A | Philippines | 122.56444 | 10.69694
Mandaluyong | N/A | Philippines | 121.0409 | 14.5832
Mandaue City | N/A | Philippines | 123.92222 | 10.32361
Arkhangelsky District | N/A | Russia | N/A | N/A
Chelyabinsk | N/A | Russia | 61.42915 | 55.15402
Izhevsk | N/A | Russia | 53.20448 | 56.84976
Kazan’ | N/A | Russia | 49.12214 | 55.78874
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow Region | N/A | Russia | N/A | N/A
Nizny Novgorod | N/A | Russia | N/A | N/A
Orenburg | N/A | Russia | 55.0988 | 51.7727
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saratov | N/A | Russia | 46.00861 | 51.54056
Stavropol Na | N/A | Russia | N/A | N/A
Tomsk Na | N/A | Russia | N/A | N/A
Voronezh | N/A | Russia | 39.1843 | 51.67204
Bloemfontein | N/A | South Africa | 26.214 | -29.12107
Cape Town | N/A | South Africa | 18.42322 | -33.92584
Durban | N/A | South Africa | 31.0292 | -29.8579
Pretoria | N/A | South Africa | 28.18783 | -25.74486
Tainan City | N/A | Taiwan | 120.21333 | 22.99083
Taipei | N/A | Taiwan | 121.52639 | 25.05306 | 958 | 1 | 0.001044 | 1 | NCT00391222 | 1COMPLETED | 2009-04-01 | 2006-11-01 | Janssen Pharmaceutica N.V., Belgium | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000184 |
[
5
] | 1,175 | RANDOMIZED | FACTORIAL | 0TREATMENT | 2DOUBLE | false | 0ALL | null | This 4-arm study will compare the efficacy and safety of PEGASYS induction and maintenance dosing, versus standard fixed dosing in combination with Copegus, and the efficacy and safety of higher dose versus standard dose Copegus in combination with PEGASYS. Patients with chronic hepatitis C (CHC) genotype 1 infection of high viral titer, and baseline body weight ≥85 kg, will be randomized to one of 4 groups, to receive one of the following: a) PEGASYS 180 µg subcutaneously (sc) weekly plus Copegus 1200 mg orally (po) daily; b) PEGASYS 180 µg sc weekly plus Copegus 1400-1600 mg po daily; c)PEGASYS 360 µg sc weekly (induction) followed by 180 µg sc weekly (maintenance) plus Copegus 1200 mg po daily; or d) PEGASYS 360 µg sc weekly (induction) followed by 180 µg sc weekly (maintenance) plus Copegus 1400-1600 mg po daily. Following 48 weeks treatment, there will be a 24-week period of treatment-free follow-up. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals. | null | Hepatitis C, Chronic | null | 4 | arm 1: None arm 2: None arm 3: None arm 4: None | [
0,
0,
0,
0
] | 4 | [
0,
0,
0,
0
] | intervention 1: 180 µg sc weekly for 48 weeks intervention 2: 1200 mg po daily for 48 weeks intervention 3: 360 µg sc weekly decreasing to 180 µg sc weekly for 48 weeks intervention 4: 1400-1600 mg po daily for 48 weeks | intervention 1: peginterferon alfa-2a intervention 2: Ribavirin intervention 3: peginterferon alfa-2a intervention 4: Ribavirin | 184 | Birmingham | Alabama | United States | -86.80249 | 33.52066
Huntsville | Alabama | United States | -86.58594 | 34.7304
Anchorage | Alaska | United States | -149.90028 | 61.21806
Phoenix | Arizona | United States | -112.07404 | 33.44838
Fresno | California | United States | -119.77237 | 36.74773
La Jolla | California | United States | -117.2742 | 32.84727
Lancaster | California | United States | -118.13674 | 34.69804
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Sacramento | California | United States | -121.4944 | 38.58157
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Diego | California | United States | -117.16472 | 32.71571
San Luis Obispo | California | United States | -120.65962 | 35.28275
San Marcos | California | United States | -117.16614 | 33.14337
Ventura | California | United States | -119.29317 | 34.27834
Aurora | Colorado | United States | -104.83192 | 39.72943
Englewood | Colorado | United States | -104.98776 | 39.64777
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Jacksonville | Florida | United States | -81.65565 | 30.33218
Jacksonville | Florida | United States | -81.65565 | 30.33218
Miami | Florida | United States | -80.19366 | 25.77427
North Miami Beach | Florida | United States | -80.16255 | 25.93315
Sarasota | Florida | United States | -82.53065 | 27.33643
Atlanta | Georgia | United States | -84.38798 | 33.749
Austell | Georgia | United States | -84.63438 | 33.81261
Marietta | Georgia | United States | -84.54993 | 33.9526
Honolulu | Hawaii | United States | -157.85833 | 21.30694
Chicago | Illinois | United States | -87.65005 | 41.85003
Chicago | Illinois | United States | -87.65005 | 41.85003
Winfield | Illinois | United States | -88.1609 | 41.8617
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Des Moines | Iowa | United States | -93.60911 | 41.60054
Iowa City | Iowa | United States | -91.53017 | 41.66113
Iowa City | Iowa | United States | -91.53017 | 41.66113
Louisville | Kentucky | United States | -85.75941 | 38.25424
Baton Rouge | Louisiana | United States | -91.18747 | 30.44332
New Orleans | Louisiana | United States | -90.07507 | 29.95465
Boston | Massachusetts | United States | -71.05977 | 42.35843
Worcester | Massachusetts | United States | -71.80229 | 42.26259
Detroit | Michigan | United States | -83.04575 | 42.33143
Ypsilanti | Michigan | United States | -83.61299 | 42.24115
Plymouth | Minnesota | United States | -93.45551 | 45.01052
Kansas City | Missouri | United States | -94.57857 | 39.09973
St Louis | Missouri | United States | -90.19789 | 38.62727
St Louis | Missouri | United States | -90.19789 | 38.62727
Lebanon | New Hampshire | United States | -72.25176 | 43.64229
Egg Harbour Township | New Jersey | United States | N/A | N/A
Vineland | New Jersey | United States | -75.02573 | 39.48623
Manhasset | New York | United States | -73.69957 | 40.79788
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Rochester | New York | United States | -77.61556 | 43.15478
The Bronx | New York | United States | -73.86641 | 40.84985
Williamsville | New York | United States | -78.73781 | 42.96395
Yonkers | New York | United States | -73.89789 | 40.9304
Asheville | North Carolina | United States | -82.55402 | 35.60095
Chapel Hill | North Carolina | United States | -79.05584 | 35.9132
Fayetteville | North Carolina | United States | -78.87836 | 35.05266
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cleveland | Ohio | United States | -81.69541 | 41.4995
Cleveland | Ohio | United States | -81.69541 | 41.4995
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Medford | Oregon | United States | -122.87559 | 42.32652
Lancaster | Pennsylvania | United States | -76.30551 | 40.03788
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Pittsburgh | Pennsylvania | United States | -79.99589 | 40.44062
Cranston | Rhode Island | United States | -71.43728 | 41.77982
Providence | Rhode Island | United States | -71.41283 | 41.82399
Columbia | South Carolina | United States | -81.03481 | 34.00071
Germantown | Tennessee | United States | -89.81009 | 35.08676
West Nashville | Tennessee | United States | -86.84639 | 36.15895
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Fort Sam Houston | Texas | United States | -98.4417 | 29.45303
Houston | Texas | United States | -95.36327 | 29.76328
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Annandale | Virginia | United States | -77.19637 | 38.83039
Charlottesville | Virginia | United States | -78.47668 | 38.02931
Chesapeake | Virginia | United States | -76.27494 | 36.81904
Fairfax | Virginia | United States | -77.30637 | 38.84622
Richmond | Virginia | United States | -77.46026 | 37.55376
Seattle | Washington | United States | -122.33207 | 47.60621
Tacoma | Washington | United States | -122.44429 | 47.25288
Vancouver | Washington | United States | -122.66149 | 45.63873
Casper | Wyoming | United States | -106.31308 | 42.86663
Cheyenne | Wyoming | United States | -104.82025 | 41.13998
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Ghent | N/A | Belgium | 3.71667 | 51.05
Leuven | N/A | Belgium | 4.70093 | 50.87959
Caixa | N/A | Brazil | N/A | N/A
Campinas | N/A | Brazil | -47.06083 | -22.90556
Juiz de Fora | N/A | Brazil | -43.35028 | -21.76417
Porto Alegre | N/A | Brazil | -51.23019 | -30.03283
Porto Alegre | N/A | Brazil | -51.23019 | -30.03283
Salvador | N/A | Brazil | -38.49096 | -12.97563
São José do Rio Preto | N/A | Brazil | -49.37944 | -20.81972
São Paulo | N/A | Brazil | -46.63611 | -23.5475
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Vancouver | British Columbia | Canada | -123.11934 | 49.24966
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
London | Ontario | Canada | -81.23304 | 42.98339
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Montreal | Quebec | Canada | -73.58781 | 45.50884
Kolding | N/A | Denmark | 9.47216 | 55.4904
Odense | N/A | Denmark | 10.38831 | 55.39594
Clermont-Ferrand | N/A | France | 3.08682 | 45.77969
Clichy | N/A | France | 2.30952 | 48.90018
Lille | N/A | France | 3.05858 | 50.63297
Lyon | N/A | France | 4.84671 | 45.74846
Rouen | N/A | France | 1.09932 | 49.44313
Strasbourg | N/A | France | 7.74553 | 48.58392
Berlin | N/A | Germany | 13.41053 | 52.52437
Bonn | N/A | Germany | 7.09549 | 50.73438
Cologne | N/A | Germany | 6.95 | 50.93333
Düsseldorf | N/A | Germany | 6.77616 | 51.22172
Frankfurt am Main | N/A | Germany | 8.68417 | 50.11552
Freiburg im Breisgau | N/A | Germany | 7.85222 | 47.9959
Giessen | N/A | Germany | 8.67554 | 50.58727
Hamburg | N/A | Germany | 9.99302 | 53.55073
Hanover | N/A | Germany | 9.73322 | 52.37052
Heidelberg | N/A | Germany | 8.69079 | 49.40768
Kiel | N/A | Germany | 10.13489 | 54.32133
Tübingen | N/A | Germany | 9.05222 | 48.52266
Békéscsaba | N/A | Hungary | 21.1 | 46.68333
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Debrecen | N/A | Hungary | 21.62444 | 47.53167
Győr | N/A | Hungary | 17.63512 | 47.68333
Gyula | N/A | Hungary | 21.28333 | 46.65
Pécs | N/A | Hungary | 18.23083 | 46.0725
Szombathely | N/A | Hungary | 16.62155 | 47.23088
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Leiden | N/A | Netherlands | 4.49306 | 52.15833
Rotterdam | N/A | Netherlands | 4.47917 | 51.9225
Bydgoszcz | N/A | Poland | 18.00762 | 53.1235
Chorzów | N/A | Poland | 18.9742 | 50.30582
Kielce | N/A | Poland | 20.62752 | 50.87033
Lodz | N/A | Poland | 19.47395 | 51.77058
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wroclaw | N/A | Poland | 17.03333 | 51.1
Ponce | N/A | Puerto Rico | -66.62398 | 18.01031
San Juan | N/A | Puerto Rico | -66.10572 | 18.46633
Santurce | N/A | Puerto Rico | -67.14018 | 18.19523
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Cluj-Napoca | N/A | Romania | 23.6 | 46.76667
Constanța | N/A | Romania | 28.63432 | 44.18073
Iași | N/A | Romania | 27.6 | 47.16667
Timișoara | N/A | Romania | 21.22571 | 45.75372
Jaloslave | N/A | Russia | N/A | N/A
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Nizhny Novgorod | N/A | Russia | 44.00205 | 56.32867
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Samara | N/A | Russia | 50.15 | 53.20007
Smolensk | N/A | Russia | 32.04371 | 54.77944
Stavropol | N/A | Russia | 41.9734 | 45.0428
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Uppsala | N/A | Sweden | 17.63889 | 59.85882
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853
Newcastle upon Tyne | N/A | United Kingdom | -1.61396 | 54.97328
Plymouth | N/A | United Kingdom | -4.14305 | 50.37153
Southampton | N/A | United Kingdom | -1.40428 | 50.90395 | 1,145 | 2 | 0.001747 | 1 | NCT00394277 | 1COMPLETED | 2009-04-01 | 2007-02-01 | Hoffmann-La Roche | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000479 | |
[
4
] | 352 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | null | The purpose of this study is to investigate the efficacy, safety, and tolerability of an investigational treatment for patients with HIV. | null | HIV Infection | treatment experienced | null | 2 | arm 1: Arm 1: MK0518 (raltegravir) + placebo to KALETRA™ (lopinavir (+) ritonavir ) arm 2: Arm 2: KALETRA™ (lopinavir (+) ritonavir) + placebo to MK0518 (raltegravir) | [
0,
1
] | 4 | [
0,
0,
0,
0
] | intervention 1: MK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d) for up to 48 weeks of treatment intervention 2: KALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) for up to 48 weeks of treatment. intervention 3: MK0518 (raltegravir) 400 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment intervention 4: KALETRA™ (lopinavir (+) ritonavir ) 400/100 mg by mouth (PO) twice daily (b.i.d.) Placebo for up to 48 weeks of treatment. | intervention 1: MK0518 (raltegravir) intervention 2: Comparator: KALETRA™ (lopinavir (+) ritonavir ) intervention 3: Comparator: placebo intervention 4: Comparator: placebo | 0 | null | 348 | 1 | 0.002874 | 1 | NCT00443703 | 6TERMINATED | 2009-04-01 | 2007-05-01 | Merck Sharp & Dohme LLC | 4INDUSTRY | false | false | false | null | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000507 |
[
3
] | 278 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | true | The objective of the study is to select an optimal dose of taribavirin by comparing the efficacy and safety of 3 taribavirin dose levels, 20, 25, and 30 mg/kg/day, versus ribavirin 800 to 1400 mg/day based on body weight, both administered in combination with peginterferon alfa-2b to therapy-naive patients with chronic Hepatitis C Virus (HCV) genotype 1 infection. | The objective of the study is to select an optimal dose of taribavirin by comparing the efficacy and safety of 3 taribavirin dose levels, 20, 25, and 30 mg/kg/day, versus ribavirin 800 mg/day to 1400 mg/day based on subject body weight, with both drugs administered in combination with peginterferon alfa-2b to therapy-naive patients with chronic Hepatitis C Virus genotype 1 infection. | Chronic Hepatitis C | Phase 2b Dose-Ranging Study | null | 4 | arm 1: Oral taribavirin tablet 20 mg/kg/day (Actual doses were 20-24 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk) arm 2: Oral taribavirin tablet 25 mg/kg/day (Actual doses were 25-29 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk) arm 3: Oral taribavirin 30 mg/kg/day (Actual doses were 30-34 mg/kg/day) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk) arm 4: Oral ribavirin 800 mg/day (body weight \<65 kg), 1000 mg/day (body weight 65-84 kg), 1200 mg/day (body weight 85-104 kg) or 1400 mg/day (body weight greater than or equal to 105 kg) BID plus weekly subcutaneous injections of peginterferon alfa-2b (1.5 ug/kg/wk) | [
0,
0,
0,
1
] | 4 | [
0,
0,
0,
0
] | intervention 1: Oral (200 mg) Tablet: 20mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period. intervention 2: Oral (200 mg) Tablet: 25mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period. intervention 3: Oral (200mg)Tablet: 30mg/kg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period. intervention 4: Oral (200mg)Tablet: 800 mg/day, 1000 mg/day, 1200 mg/day, or 1400 mg/day BID, patients will be treated for a total of 48 weeks. in addition, all patients will receive peginterferon alfa-2b (PEG-Intron) by weekly subcutaneous injection. Patients who complete treatment with study drug or discontinue treatment prematurely will enter a 24-week follow-up period. | intervention 1: Taribavirin intervention 2: Taribavirin intervention 3: Taribavirin intervention 4: Ribavirin | 1 | Los Angeles | California | United States | -118.24368 | 34.05223 | 275 | 1 | 0.003636 | 1 | NCT00446134 | 1COMPLETED | 2009-04-01 | 2007-03-01 | Bausch Health Americas, Inc. | 4INDUSTRY | false | false | false | null | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000642 |
[
3
] | 207 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | false | Study (07-IN-NX003) is a Phase 2, multi-center, placebo-controlled, double-blind, randomized, dose-escalation trial. It is designed to investigate the safety, efficacy and tolerability of NKTR-118 (PEG-naloxol) in patients with opioid-induced constipation (OIC) and other clinical manifestations of opioid-induced bowel dysfunction (OBD). The objective of this study is to evaluate the safety, effectiveness and pharmacokinetics of NKTR-118 at 4 different doses. | null | Opioid Induced Constipation (OIC) | NKTR, constipation, opioid, induced, bowel, dysfunction, Naloxol, Naloxone, Narcan, PEG naloxol, OIC, OBD, Nektar | null | 2 | arm 1: Placebo arm 2: NKTR-118 | [
2,
0
] | 2 | [
0,
0
] | intervention 1: placebo, oral, once daily (QD) intervention 2: 5 mg, 25 mg, 50 mg or 100 mg, oral,once daily (QD) | intervention 1: placebo intervention 2: NKTR-118 | 33 | Huntsville | Alabama | United States | -86.58594 | 34.7304
Pinson | Alabama | United States | -86.68332 | 33.68899
Tucson | Arizona | United States | -110.92648 | 32.22174
Laguna Hills | California | United States | -117.71283 | 33.61252
San Diego | California | United States | -117.16472 | 32.71571
Littleton | Colorado | United States | -105.01665 | 39.61332
Chiefland | Florida | United States | -82.85984 | 29.47496
Melbourne | Florida | United States | -80.60811 | 28.08363
West Palm Beach | Florida | United States | -80.05337 | 26.71534
Weston | Florida | United States | -80.39977 | 26.10037
Atlanta | Georgia | United States | -84.38798 | 33.749
Boise | Idaho | United States | -116.20345 | 43.6135
Bloomington | Illinois | United States | -88.99369 | 40.4842
Chicago | Illinois | United States | -87.65005 | 41.85003
Indianapolis | Indiana | United States | -86.15804 | 39.76838
Lexington | Kentucky | United States | -84.47772 | 37.98869
Baton Rouge | Louisiana | United States | -91.18747 | 30.44332
Elkridge | Maryland | United States | -76.71358 | 39.21261
Edina | Minnesota | United States | -93.34995 | 44.88969
City of Saint Peters | Missouri | United States | -90.62651 | 38.80033
Albuquerque | New Mexico | United States | -106.65114 | 35.08449
Great Neck | New York | United States | -73.72846 | 40.80066
Flat Rock | North Carolina | United States | -82.44151 | 35.27123
Winston-Salem | North Carolina | United States | -80.24422 | 36.09986
Canton | Ohio | United States | -81.37845 | 40.79895
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Tulsa | Oklahoma | United States | -95.99277 | 36.15398
Medford | Oregon | United States | -122.87559 | 42.32652
Anderson | South Carolina | United States | -82.65013 | 34.50344
Orangeburg | South Carolina | United States | -80.85565 | 33.49182
Chattanooga | Tennessee | United States | -85.30968 | 35.04563
Salt Lake City | Utah | United States | -111.89105 | 40.76078
Spokane | Washington | United States | -117.42908 | 47.65966 | 194 | 1 | 0.005155 | 1 | NCT00600119 | 1COMPLETED | 2009-04-01 | 2007-12-01 | AstraZeneca | 4INDUSTRY | false | false | false | null | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000911 |
[
5
] | 6,586 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | This study will provide treatment with erlotinib to participants with advanced NSCLC who have received at least one course of standard chemotherapy or radiation therapy, or who are not medically suitable for either. Efficacy and safety will be monitored throughout the study. | null | Non-Small Cell Lung Cancer | null | 1 | arm 1: Erlotinib will be given as a single agent in this expanded access program (EAP) to participants with inoperable, locally advanced, recurrent, or metastatic NSCLC. Treatment will continue until unacceptable toxicity, disease progression, or withdrawal for any other reason. | [
0
] | 1 | [
0
] | intervention 1: Erlotinib will be given orally as 150 milligrams (mg) once daily until unacceptable toxicity, disease progression, or withdrawal for any other reason. | intervention 1: Erlotinib | 543 | Tirana | N/A | Albania | 19.81866 | 41.32744
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Buenos Aires | N/A | Argentina | -58.37723 | -34.61315
Córdoba | N/A | Argentina | -64.18853 | -31.40648
La Plata | N/A | Argentina | -57.95442 | -34.92126
Salta | N/A | Argentina | -65.41999 | -24.80645
Santa Fe | N/A | Argentina | -60.70868 | -31.64881
Adelaide | N/A | Australia | 138.59863 | -34.92866
Camperdown | N/A | Australia | 151.17642 | -33.88965
Chermside | N/A | Australia | 153.03062 | -27.38472
Frankston | N/A | Australia | 145.12291 | -38.14458
Fremantle | N/A | Australia | 115.74557 | -32.05632
Geelong | N/A | Australia | 144.36069 | -38.14711
Kurralta Park | N/A | Australia | 138.56702 | -34.95142
Malvern | N/A | Australia | 145.02811 | -37.86259
Melbourne | N/A | Australia | 144.96332 | -37.814
Melbourne | N/A | Australia | 144.96332 | -37.814
Perth | N/A | Australia | 115.8614 | -31.95224
St Leonards | N/A | Australia | 151.19836 | -33.82344
Sydney | N/A | Australia | 151.20732 | -33.86785
Sydney | N/A | Australia | 151.20732 | -33.86785
Tugun | N/A | Australia | 153.5 | -28.15
Waratah | N/A | Australia | 151.72647 | -32.90667
Wodonga | N/A | Australia | 146.88809 | -36.12179
Wollongong | N/A | Australia | 150.89345 | -34.424
Bludesch | N/A | Austria | 9.73306 | 47.2
Grimmenstein | N/A | Austria | 16.12724 | 47.61635
Innsbruck | N/A | Austria | 11.39454 | 47.26266
Klagenfurt | N/A | Austria | 14.30528 | 46.62472
Kufstein | N/A | Austria | 12.16667 | 47.58333
Leoben | N/A | Austria | 15.09144 | 47.3765
Linz | N/A | Austria | 14.28611 | 48.30639
Linz | N/A | Austria | 14.28611 | 48.30639
Natters | N/A | Austria | 11.37342 | 47.23414
Oberpullendorf | N/A | Austria | 16.50447 | 47.50352
Salzburg | N/A | Austria | 13.04399 | 47.79941
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Vienna | N/A | Austria | 16.37208 | 48.20849
Wels | N/A | Austria | 14.03333 | 48.16667
Zams | N/A | Austria | 10.5897 | 47.15844
Aalst | N/A | Belgium | 4.0355 | 50.93604
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Antwerp | N/A | Belgium | 4.40026 | 51.22047
Arlon | N/A | Belgium | 5.81667 | 49.68333
Baudour | N/A | Belgium | 3.8332 | 50.48296
Blankenberge | N/A | Belgium | 3.13227 | 51.31306
Borgerhout | N/A | Belgium | 4.43539 | 51.20957
Boussu | N/A | Belgium | 3.7944 | 50.43417
Brasschaat | N/A | Belgium | 4.49182 | 51.2912
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Charleroi | N/A | Belgium | 4.44448 | 50.41136
Edegem | N/A | Belgium | 4.44504 | 51.15662
Genk | N/A | Belgium | 5.50082 | 50.965
Ghent | N/A | Belgium | 3.71667 | 51.05
Gilly | N/A | Belgium | 4.4789 | 50.42449
Godinne | N/A | Belgium | 4.87364 | 50.34809
Gosselies | N/A | Belgium | 4.43324 | 50.46936
Haine-Saint-Paul | N/A | Belgium | 4.1885 | 50.45544
Hasselt | N/A | Belgium | 5.33781 | 50.93106
Kortrijk | N/A | Belgium | 3.26487 | 50.82803
Libramont | N/A | Belgium | 5.37318 | 49.91741
Liège | N/A | Belgium | 5.56749 | 50.63373
Mons | N/A | Belgium | 3.95229 | 50.45413
Namur | N/A | Belgium | 4.86746 | 50.4669
Ostend | N/A | Belgium | 2.927 | 51.21551
Ottignies | N/A | Belgium | 4.56679 | 50.66535
Oudenaarde | N/A | Belgium | 3.60891 | 50.85168
Roeselare | N/A | Belgium | 3.12269 | 50.94653
Sint-Niklaas | N/A | Belgium | 4.1437 | 51.16509
Tielt | N/A | Belgium | 3.32707 | 50.99931
Tournai | N/A | Belgium | 3.38932 | 50.60715
Turnhout | N/A | Belgium | 4.94471 | 51.32254
Wilrijk | N/A | Belgium | 4.39513 | 51.16734
Banja Luka | N/A | Bosnia and Herzegovina | 17.19386 | 44.77842
Sarajevo | N/A | Bosnia and Herzegovina | 18.35644 | 43.84864
Belo Horizonte | N/A | Brazil | -43.93778 | -19.92083
Belo Horizonte | N/A | Brazil | -43.93778 | -19.92083
Belo Horizonte | N/A | Brazil | -43.93778 | -19.92083
Belo Horizonte | N/A | Brazil | -43.93778 | -19.92083
Brasília | N/A | Brazil | -47.92972 | -15.77972
Brasília | N/A | Brazil | -47.92972 | -15.77972
Campinas | N/A | Brazil | -47.06083 | -22.90556
Campinas | N/A | Brazil | -47.06083 | -22.90556
Caxias do Sul | N/A | Brazil | -51.17944 | -29.16806
Curitiba | N/A | Brazil | -49.27306 | -25.42778
Curitiba | N/A | Brazil | -49.27306 | -25.42778
Curitiba | N/A | Brazil | -49.27306 | -25.42778
Fortaleza | N/A | Brazil | -38.54306 | -3.71722
Fortaleza | N/A | Brazil | -38.54306 | -3.71722
Fortaleza | N/A | Brazil | -38.54306 | -3.71722
Ijuí | N/A | Brazil | -53.91472 | -28.38778
Jaú | N/A | Brazil | -48.55778 | -22.29639
João Pessoa | N/A | Brazil | -34.86306 | -7.115
Porto Alegre | N/A | Brazil | -51.23019 | -30.03283
Porto Alegre | N/A | Brazil | -51.23019 | -30.03283
Porto Alegre | N/A | Brazil | -51.23019 | -30.03283
Porto Alegre | N/A | Brazil | -51.23019 | -30.03283
Recife | N/A | Brazil | -34.88111 | -8.05389
Ribeirão Preto | N/A | Brazil | -47.81028 | -21.1775
Rio de Janeiro | N/A | Brazil | -43.18223 | -22.90642
Rio de Janeiro | N/A | Brazil | -43.18223 | -22.90642
Rio de Janeiro | N/A | Brazil | -43.18223 | -22.90642
Rio de Janeiro | N/A | Brazil | -43.18223 | -22.90642
Salvador | N/A | Brazil | -38.49096 | -12.97563
Salvador | N/A | Brazil | -38.49096 | -12.97563
Salvador | N/A | Brazil | -38.49096 | -12.97563
Santos | N/A | Brazil | -46.33361 | -23.96083
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
São Paulo | N/A | Brazil | -46.63611 | -23.5475
Sorocaba | N/A | Brazil | -47.45806 | -23.50167
Plovdiv | N/A | Bulgaria | 24.75 | 42.15
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Sofia | N/A | Bulgaria | 23.32415 | 42.69751
Varna | N/A | Bulgaria | 27.91667 | 43.21667
Santiago | N/A | Chile | -70.64827 | -33.45694
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Beijing | N/A | China | 116.39723 | 39.9075
Chengdu | N/A | China | 104.06667 | 30.66667
Guangzhou | N/A | China | 113.25 | 23.11667
Guangzhou | N/A | China | 113.25 | 23.11667
Hangzhou | N/A | China | 120.16142 | 30.29365
Harbin | N/A | China | 126.65 | 45.75
Nanjing | N/A | China | 118.77778 | 32.06167
Shanghai | N/A | China | 121.45806 | 31.22222
Shanghai | N/A | China | 121.45806 | 31.22222
Shanghai | N/A | China | 121.45806 | 31.22222
Tianjin | N/A | China | 117.17667 | 39.14222
Wuhan | N/A | China | 114.26667 | 30.58333
Bogotá | N/A | Colombia | -74.08175 | 4.60971
Santiago de Cali | N/A | Colombia | -76.5199 | 3.43054
Zagreb | N/A | Croatia | 15.97798 | 45.81444
Brno | N/A | Czechia | 16.60796 | 49.19522
Hradec Králové | N/A | Czechia | 15.83277 | 50.20923
Olomouc | N/A | Czechia | 17.25175 | 49.59552
Pilsen | N/A | Czechia | 13.37759 | 49.74747
Prague | N/A | Czechia | 14.42076 | 50.08804
Guayaquil | N/A | Ecuador | -79.88621 | -2.19616
Quito | N/A | Ecuador | -78.52495 | -0.22985
Cairo | N/A | Egypt | 31.24967 | 30.06263
Giza | N/A | Egypt | 31.20861 | 30.00944
Giza | N/A | Egypt | 31.20861 | 30.00944
Tallinn | N/A | Estonia | 24.75353 | 59.43696
Tartu | N/A | Estonia | 26.72509 | 58.38062
Hämeenlinna | N/A | Finland | 24.46434 | 60.99596
Helsinki | N/A | Finland | 24.93545 | 60.16952
Helsinki | N/A | Finland | 24.93545 | 60.16952
Joensuu | N/A | Finland | 29.76316 | 62.60118
Kuopio | N/A | Finland | 27.67703 | 62.89238
Oulu | N/A | Finland | 25.46816 | 65.01236
Pori | N/A | Finland | 21.78333 | 61.48333
Tampere | N/A | Finland | 23.78712 | 61.49911
Turku | N/A | Finland | 22.26869 | 60.45148
Vaasa | N/A | Finland | 21.61577 | 63.096
Amberg | N/A | Germany | 11.86267 | 49.44287
Augsburg | N/A | Germany | 10.89851 | 48.37154
Aurich | N/A | Germany | 7.48232 | 53.46919
Bad Berka | N/A | Germany | 11.28245 | 50.89982
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Bonn | N/A | Germany | 7.09549 | 50.73438
Celle | N/A | Germany | 10.08047 | 52.62264
Cologne | N/A | Germany | 6.95 | 50.93333
Cologne | N/A | Germany | 6.95 | 50.93333
Dortmund | N/A | Germany | 7.466 | 51.51494
Dresden | N/A | Germany | 13.73832 | 51.05089
Essen | N/A | Germany | 7.01228 | 51.45657
Flensburg | N/A | Germany | 9.43722 | 54.78805
Frankfurt | N/A | Germany | 10.53333 | 49.68333
Frankfurt am Main | N/A | Germany | 8.68417 | 50.11552
Freiburg im Breisgau | N/A | Germany | 7.85222 | 47.9959
Gauting | N/A | Germany | 11.37703 | 48.06919
Gerlingen | N/A | Germany | 9.06316 | 48.79954
Giessen | N/A | Germany | 8.67554 | 50.58727
Großhansdorf | N/A | Germany | 10.28333 | 53.66667
Halle | N/A | Germany | 11.97947 | 51.48158
Hamburg | N/A | Germany | 9.99302 | 53.55073
Hamburg | N/A | Germany | 9.99302 | 53.55073
Heidelberg | N/A | Germany | 8.69079 | 49.40768
Herne | N/A | Germany | 7.22572 | 51.5388
Homburg/Saar | N/A | Germany | N/A | N/A
Kassel | N/A | Germany | 9.5 | 51.31667
Koblenz | N/A | Germany | 7.57883 | 50.35357
Leipzig | N/A | Germany | 12.37129 | 51.33962
Leverkusen | N/A | Germany | 6.98432 | 51.0303
Lostau | N/A | Germany | 11.73795 | 52.20871
Löwenstein | N/A | Germany | 9.38 | 49.09558
Lübeck | N/A | Germany | 10.68729 | 53.86893
Mainz | N/A | Germany | 8.2791 | 49.98419
Mannheim | N/A | Germany | 8.46694 | 49.4891
Minden | N/A | Germany | 8.91455 | 52.28953
Mönchengladbach | N/A | Germany | 6.44172 | 51.18539
München | N/A | Germany | 13.31243 | 51.60698
München | N/A | Germany | 13.31243 | 51.60698
München | N/A | Germany | 13.31243 | 51.60698
Neuruppin | N/A | Germany | 12.80311 | 52.92815
Nuremberg | N/A | Germany | 11.07752 | 49.45421
Oldenburg | N/A | Germany | 8.21467 | 53.14118
Osnabrück | N/A | Germany | 8.0498 | 52.27264
Rostock | N/A | Germany | 12.14049 | 54.0887
Saarbrücken | N/A | Germany | 7.00982 | 49.23262
Trier | N/A | Germany | 6.63935 | 49.75565
Ulm | N/A | Germany | 9.99155 | 48.39841
Wangen | N/A | Germany | 9.83247 | 47.6895
Wiesbaden | N/A | Germany | 8.24932 | 50.08258
Wuppertal | N/A | Germany | 7.14816 | 51.25627
Würselen | N/A | Germany | 6.1347 | 50.81809
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Athens | N/A | Greece | 23.72784 | 37.98376
Haidari | N/A | Greece | N/A | N/A
Heraklion | N/A | Greece | 25.14341 | 35.32787
Neo Faliro | N/A | Greece | 23.66736 | 37.9464
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Thessaloniki | N/A | Greece | 22.93086 | 40.64361
Guatemala City | N/A | Guatemala | -90.51327 | 14.64072
Hong Kong | N/A | Hong Kong | 114.17469 | 22.27832
Hong Kong | N/A | Hong Kong | 114.17469 | 22.27832
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Budapest | N/A | Hungary | 19.04045 | 47.49835
Deszk | N/A | Hungary | 20.24322 | 46.21802
Kecskemét | N/A | Hungary | 19.69128 | 46.90618
Mátraháza | N/A | Hungary | 19.97981 | 47.87124
Nyíregyháza | N/A | Hungary | 21.71671 | 47.95539
Pécs | N/A | Hungary | 18.23083 | 46.0725
Törökbálint | N/A | Hungary | 18.91356 | 47.42931
Bangalore | N/A | India | 77.59369 | 12.97194
New Delhi | N/A | India | 77.2148 | 28.62137
New Delhi | N/A | India | 77.2148 | 28.62137
Pune | N/A | India | 73.85535 | 18.51957
Vellore | N/A | India | 79.13255 | 12.9184
Jakarta | N/A | Indonesia | 106.84513 | -6.21462
Cork | N/A | Ireland | -8.47061 | 51.89797
Dublin | N/A | Ireland | -6.24889 | 53.33306
Dublin | N/A | Ireland | -6.24889 | 53.33306
Dublin | N/A | Ireland | -6.24889 | 53.33306
Dublin | N/A | Ireland | -6.24889 | 53.33306
Galway | N/A | Ireland | -9.05095 | 53.27245
Ashkelon | N/A | Israel | 34.57149 | 31.66926
Beersheba | N/A | Israel | 34.7913 | 31.25181
Haifa | N/A | Israel | 34.99928 | 32.81303
Haifa | N/A | Israel | 34.99928 | 32.81303
Holon | N/A | Israel | 34.77918 | 32.01034
Jerusalem | N/A | Israel | 35.21633 | 31.76904
Jerusalem | N/A | Israel | 35.21633 | 31.76904
Kfar Saba | N/A | Israel | 34.90694 | 32.175
Nahariya | N/A | Israel | 35.09814 | 33.00892
Petah Tikva | N/A | Israel | 34.88747 | 32.08707
Ramat Gan | N/A | Israel | 34.81065 | 32.08227
Rehovot | N/A | Israel | 34.81199 | 31.89421
Safed | N/A | Israel | 35.496 | 32.96465
Tel Aviv | N/A | Israel | 34.78057 | 32.08088
Ẕerifin | N/A | Israel | 34.84852 | 31.95731
Ancona | N/A | Italy | 13.5103 | 43.60717
Avellino | N/A | Italy | 14.79103 | 40.91494
Aviano | N/A | Italy | 12.59472 | 46.07056
Bari | N/A | Italy | 16.86982 | 41.12066
Benevento | N/A | Italy | 14.77816 | 41.1307
Bergamo | N/A | Italy | 9.66721 | 45.69601
Bollate | N/A | Italy | 9.12054 | 45.54647
Bologna | N/A | Italy | 11.33875 | 44.49381
Bologna | N/A | Italy | 11.33875 | 44.49381
Brescia | N/A | Italy | 10.21472 | 45.53558
Candiolo | N/A | Italy | 7.59812 | 44.95858
Catania | N/A | Italy | 15.07041 | 37.49223
Catanzaro | N/A | Italy | 16.60086 | 38.88247
Cosenza | N/A | Italy | 16.25307 | 39.2989
Cuneo | N/A | Italy | 7.54828 | 44.39071
Fabriano | N/A | Italy | 12.90327 | 43.33941
Feltre - Bl | N/A | Italy | N/A | N/A
Florence | N/A | Italy | 11.24626 | 43.77925
Genova | N/A | Italy | 11.87211 | 45.21604
La Spezia | N/A | Italy | 9.82375 | 44.103
Lido di Camaiore | N/A | Italy | 10.2269 | 43.90012
Livorno | N/A | Italy | 10.32615 | 43.54427
Meldola | N/A | Italy | 12.0626 | 44.12775
Messina | N/A | Italy | 15.55256 | 38.19394
Milan | N/A | Italy | 12.59836 | 42.78235
Milan | N/A | Italy | 12.59836 | 42.78235
Milan | N/A | Italy | 12.59836 | 42.78235
Mirano | N/A | Italy | 12.10775 | 45.49458
Modena | N/A | Italy | 10.92539 | 44.64783
Napoli | N/A | Italy | 14.5195 | 40.87618
Napoli | N/A | Italy | 14.5195 | 40.87618
Nuoro | N/A | Italy | 9.32568 | 40.31991
Orbassano | N/A | Italy | 7.53813 | 45.00547
Palermo | N/A | Italy | 13.3636 | 38.1166
Palermo | N/A | Italy | 13.3636 | 38.1166
Parma | N/A | Italy | 10.32618 | 44.79935
Pavia | N/A | Italy | 9.15917 | 45.19205
Perugia | N/A | Italy | 12.38878 | 43.1122
Pescara | N/A | Italy | 14.20283 | 42.4584
Pisa | N/A | Italy | 10.4036 | 43.70853
Rionero in Vulture | N/A | Italy | 15.6711 | 40.92328
Roma | N/A | Italy | 11.10642 | 44.99364
Roma | N/A | Italy | 11.10642 | 44.99364
Roma | N/A | Italy | 11.10642 | 44.99364
Roma | N/A | Italy | 11.10642 | 44.99364
Roma | N/A | Italy | 11.10642 | 44.99364
Roma | N/A | Italy | 11.10642 | 44.99364
Salerno | N/A | Italy | 14.79328 | 40.67545
Salerno | N/A | Italy | 14.79328 | 40.67545
San Giovanni Rotondo | N/A | Italy | 15.7277 | 41.70643
Sassari | N/A | Italy | 8.55552 | 40.72586
Siena | N/A | Italy | 11.33064 | 43.31822
Sondrio | N/A | Italy | 9.87134 | 46.16852
Taormina | N/A | Italy | 15.28851 | 37.85358
Torino | N/A | Italy | 11.99138 | 44.88856
Trento | N/A | Italy | 11.12108 | 46.06787
Udine | N/A | Italy | 13.23715 | 46.0693
Riga | N/A | Latvia | 24.10589 | 56.946
Riga | N/A | Latvia | 24.10589 | 56.946
Kaunas | N/A | Lithuania | 23.90961 | 54.90272
Vilnius | N/A | Lithuania | 25.2798 | 54.68916
Kuala Lumpur | N/A | Malaysia | 101.68653 | 3.1412
Acapulco | N/A | Mexico | -91.51028 | 16.11417
Chihuahua City | N/A | Mexico | -106.08889 | 28.63528
Chihuahua City | N/A | Mexico | -106.08889 | 28.63528
Guadalajara | N/A | Mexico | -103.34749 | 20.67738
Guadalajara | N/A | Mexico | -103.34749 | 20.67738
Juárez | N/A | Mexico | -93.19253 | 17.60747
León | N/A | Mexico | -113.78333 | 28.51667
León | N/A | Mexico | -113.78333 | 28.51667
Matamoros | N/A | Mexico | -103.2285 | 25.52699
Mexicali | N/A | Mexico | -115.45446 | 32.62781
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mexico City | N/A | Mexico | -99.12766 | 19.42847
Mérida | N/A | Mexico | -89.62318 | 20.967
Mérida | N/A | Mexico | -89.62318 | 20.967
Monterrey | N/A | Mexico | -100.31721 | 25.68435
Monterrey | N/A | Mexico | -100.31721 | 25.68435
Monterrey | N/A | Mexico | -100.31721 | 25.68435
Monterrey | N/A | Mexico | -100.31721 | 25.68435
Obregón | N/A | Mexico | -109.63445 | 26.82768
Obregón | N/A | Mexico | -109.63445 | 26.82768
Puebla City | N/A | Mexico | -98.20723 | 19.04778
San Luis Potosí City | N/A | Mexico | -100.97135 | 22.15234
Tampico | N/A | Mexico | -97.87777 | 22.28519
Tijuana | N/A | Mexico | -117.00371 | 32.5027
Toluca | N/A | Mexico | -99.65324 | 19.28786
Torreón | N/A | Mexico | -103.41898 | 25.54389
Zapopan | N/A | Mexico | -103.38742 | 20.72111
's-Hertogenbosch | N/A | Netherlands | 5.30417 | 51.69917
Alkmaar | N/A | Netherlands | 4.74861 | 52.63167
Amersfoort | N/A | Netherlands | 5.3875 | 52.155
Amstelveen | N/A | Netherlands | 4.86389 | 52.30083
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Amsterdam | N/A | Netherlands | 4.88969 | 52.37403
Arnhem | N/A | Netherlands | 5.91111 | 51.98
Assen | N/A | Netherlands | 6.5625 | 52.99667
Beverwijk | N/A | Netherlands | 4.65694 | 52.48333
Boxmeer | N/A | Netherlands | 5.94722 | 51.64667
Breda | N/A | Netherlands | 4.77596 | 51.58656
Capelle Ad Yssel | N/A | Netherlands | N/A | N/A
Drachten | N/A | Netherlands | 6.0989 | 53.11254
Eindhoven | N/A | Netherlands | 5.47778 | 51.44083
Enschede | N/A | Netherlands | 6.89583 | 52.21833
Flushing | N/A | Netherlands | 3.57361 | 51.4425
Groningen | N/A | Netherlands | 6.56667 | 53.21917
Groningen | N/A | Netherlands | 6.56667 | 53.21917
Haarlem | N/A | Netherlands | 4.63683 | 52.38084
Harderwijk | N/A | Netherlands | 5.62083 | 52.34167
Heerlen | N/A | Netherlands | 5.98154 | 50.88365
Helmond | N/A | Netherlands | 5.66111 | 51.48167
Hengelo | N/A | Netherlands | 6.79306 | 52.26583
Hoofddorp | N/A | Netherlands | 4.68889 | 52.3025
Leiden | N/A | Netherlands | 4.49306 | 52.15833
Leiderdorp | N/A | Netherlands | 4.52917 | 52.15833
Maastricht | N/A | Netherlands | 5.68889 | 50.84833
Nieuwegein | N/A | Netherlands | 5.08056 | 52.02917
Nijmegen | N/A | Netherlands | 5.85278 | 51.8425
Roermond | N/A | Netherlands | 5.9875 | 51.19417
Rotterdam | N/A | Netherlands | 4.47917 | 51.9225
Sliedrecht | N/A | Netherlands | 4.77639 | 51.82083
The Hague | N/A | Netherlands | 4.29861 | 52.07667
Veldhoven | N/A | Netherlands | 5.40278 | 51.41833
Venlo | N/A | Netherlands | 6.16806 | 51.37
Vlaardingen | N/A | Netherlands | 4.34167 | 51.9125
Zaandam | N/A | Netherlands | 4.82643 | 52.43854
Zwolle | N/A | Netherlands | 6.09444 | 52.5125
Christchurch | N/A | New Zealand | 172.63333 | -43.53333
Hamilton | N/A | New Zealand | 175.28333 | -37.78333
Palmerston North | N/A | New Zealand | 175.61113 | -40.35636
Wellington | N/A | New Zealand | 174.77557 | -41.28664
Panama City | N/A | Panama | -79.51973 | 8.9936
Callao | N/A | Peru | -77.13452 | -12.05162
Lima | N/A | Peru | -77.02824 | -12.04318
Lima | N/A | Peru | -77.02824 | -12.04318
Lima | N/A | Peru | -77.02824 | -12.04318
Gdansk | N/A | Poland | 18.64912 | 54.35227
Lublin | N/A | Poland | 22.56667 | 51.25
Olsztyn | N/A | Poland | 20.49416 | 53.77995
Poznan | N/A | Poland | 16.92993 | 52.40692
Warsaw | N/A | Poland | 21.01178 | 52.22977
Warsaw | N/A | Poland | 21.01178 | 52.22977
Wroclaw | N/A | Poland | 17.03333 | 51.1
Zabrze | N/A | Poland | 18.78576 | 50.32492
Lisbon | N/A | Portugal | -9.1498 | 38.72509
Porto | N/A | Portugal | -8.61099 | 41.14961
São Martinho do Bispo | N/A | Portugal | -8.45692 | 40.21021
Setúbal | N/A | Portugal | -8.8882 | 38.5244
Vila Nova de Gaia | N/A | Portugal | -8.61241 | 41.12401
Alba Iulia | N/A | Romania | 23.58333 | 46.06667
Baia Mare | N/A | Romania | 23.56808 | 47.65729
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Bucharest | N/A | Romania | 26.10626 | 44.43225
Cluj-Napoca | N/A | Romania | 23.6 | 46.76667
Oradea | N/A | Romania | 21.91833 | 47.0458
Sibiu | N/A | Romania | 24.15 | 45.8
Suceava | N/A | Romania | 26.25 | 47.63333
Timișoara | N/A | Romania | 21.22571 | 45.75372
Barnaul | N/A | Russia | 83.7456 | 53.3598
Kazan' | N/A | Russia | 49.12214 | 55.78874
Kazan' | N/A | Russia | 49.12214 | 55.78874
Krasnodar | N/A | Russia | 38.97603 | 45.04484
Krasnodar | N/A | Russia | 38.97603 | 45.04484
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Moscow | N/A | Russia | 37.61556 | 55.75222
Obninsk | N/A | Russia | 36.61238 | 55.10993
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Saint Petersburg | N/A | Russia | 30.31413 | 59.93863
Samara | N/A | Russia | 50.15 | 53.20007
Smolensk | N/A | Russia | 32.04371 | 54.77944
Stavropol | N/A | Russia | 41.9734 | 45.0428
Tyumen | N/A | Russia | 65.52722 | 57.15222
Ufa | N/A | Russia | 55.96779 | 54.74306
Volgograd | N/A | Russia | 44.50183 | 48.71939
Riyadh | N/A | Saudi Arabia | 46.72185 | 24.68773
Belgrade | N/A | Serbia | 20.46513 | 44.80401
Novi Sad | N/A | Serbia | 19.83694 | 45.25167
Banská Bystrica | N/A | Slovakia | 19.15349 | 48.73946
Bratislava | N/A | Slovakia | 17.10674 | 48.14816
Košice | N/A | Slovakia | 21.25808 | 48.71395
Nitra | N/A | Slovakia | 18.08453 | 48.30763
Poprad | N/A | Slovakia | 20.29798 | 49.06144
Ljubljana | N/A | Slovenia | 14.50513 | 46.05108
Bundang City | N/A | South Korea | N/A | N/A
Busan | N/A | South Korea | 129.03004 | 35.10168
Cheonan | N/A | South Korea | 127.1522 | 36.8065
Daegu | N/A | South Korea | 128.59111 | 35.87028
Daegu | N/A | South Korea | 128.59111 | 35.87028
Daegu | N/A | South Korea | 128.59111 | 35.87028
Daejeon | N/A | South Korea | 127.38493 | 36.34913
Gwangju | N/A | South Korea | 126.91556 | 35.15472
Iksan | N/A | South Korea | 126.95444 | 35.94389
Incheon | N/A | South Korea | 126.70515 | 37.45646
Kyunggi-do | N/A | South Korea | N/A | N/A
Pusan | N/A | South Korea | 128.3681 | 36.3809
Pusan | N/A | South Korea | 128.3681 | 36.3809
Pusan | N/A | South Korea | 128.3681 | 36.3809
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Seoul | N/A | South Korea | 126.9784 | 37.566
Suwon | N/A | South Korea | 127.00889 | 37.29111
Falun | N/A | Sweden | 15.62597 | 60.60357
Gothenburg | N/A | Sweden | 11.96679 | 57.70716
Linköping | N/A | Sweden | 15.62157 | 58.41086
Lund | N/A | Sweden | 13.19321 | 55.70584
Malmo | N/A | Sweden | 13.00073 | 55.60587
Stockholm | N/A | Sweden | 18.06871 | 59.32938
Uppsala | N/A | Sweden | 17.63889 | 59.85882
Aarau | N/A | Switzerland | 8.04422 | 47.39254
Aarau | N/A | Switzerland | 8.04422 | 47.39254
Baden | N/A | Switzerland | 8.30592 | 47.47333
Chur | N/A | Switzerland | 9.53287 | 46.84986
Locarno | N/A | Switzerland | 8.79953 | 46.17086
Lucerne | N/A | Switzerland | 8.30635 | 47.05048
Zurich | N/A | Switzerland | 8.55 | 47.36667
Changhua | N/A | Taiwan | 120.5512 | 24.0692
Kaohsiung City | N/A | Taiwan | 120.31333 | 22.61626
Kaohsiung City | N/A | Taiwan | 120.31333 | 22.61626
Kaohsiung City | N/A | Taiwan | 120.31333 | 22.61626
Taichung | N/A | Taiwan | 120.6839 | 24.1469
Taichung | N/A | Taiwan | 120.6839 | 24.1469
Tainan City | N/A | Taiwan | 120.21333 | 22.99083
Tainan City | N/A | Taiwan | 120.21333 | 22.99083
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taipei | N/A | Taiwan | 121.52639 | 25.05306
Taoyuan District | N/A | Taiwan | 121.3187 | 24.9896
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Bangkok | N/A | Thailand | 100.50144 | 13.75398
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Istanbul | N/A | Turkey (Türkiye) | 28.94966 | 41.01384
Izmir | N/A | Turkey (Türkiye) | 27.13838 | 38.41273
Izmir | N/A | Turkey (Türkiye) | 27.13838 | 38.41273
Shhiye, Ankara | N/A | Turkey (Türkiye) | 32.85427 | 39.91987
Montevideo | N/A | Uruguay | -56.18816 | -34.90328
Caracas | N/A | Venezuela | -66.87919 | 10.48801
Caracas | N/A | Venezuela | -66.87919 | 10.48801 | 6,586 | 1 | 0.000152 | 0 | NCT00949910 | 1COMPLETED | 2009-04-01 | 2004-11-01 | Hoffmann-La Roche | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.000027 | |
[
2,
3
] | 108 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | RATIONALE: Drugs used in chemotherapy, such as paclitaxel, ifosfamide, carboplatin, and etoposide work in different ways to stop the growth of tumor cells, either by killing them or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed.
The design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support.
PURPOSE: The purpose of this study is to determine the effects of an intensive sequence of chemotherapy drugs in patients with metastatic germ cell cancer. All of these chemotherapy drugs are known to be active in this disease. | OBJECTIVES:
* Determine the safety of paclitaxel and ifosfamide followed by carboplatin and etoposide with stem cell support in patients with unfavorable germ cell tumors with unfavorable prognostic factors and resistance to cisplatin.
* Determine the efficacy of this regimen as salvage therapy in these patients.
* Escalate the dose of carboplatin based on a target area under the concentration time curve and renal function, and determine the pharmacokinetics of carboplatin in selected patients.
* Determine the qualitative effects of paclitaxel and ifosfamide on hematopoietic progenitors in these patients.
OUTLINE: This is a dose escalation study of carboplatin.
* Part A: Patients receive paclitaxel IV continuously on day 1 and ifosfamide IV over 4 hours on days 2-4. Autologous peripheral blood stem cells (PBSC) are harvested on days 11-13. Filgrastim (G-CSF) is administered subcutaneously (SC) twice daily beginning 6 hours after completion of paclitaxel and ifosfamide infusions and continuing until the last day of leukapheresis. Treatment continues every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Before beginning the first course of chemotherapy, autologous bone marrow (ABM) is harvested, if possible, in case insufficient peripheral blood stem cells (PBSC) are harvested. Patients who were unable to undergo harvest of ABM before the first course of chemotherapy undergo harvest of ABM before beginning the second course of chemotherapy.
* Part B : Beginning 2 weeks after completion of regimen A, patients receive etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. PBSC are reinfused on day 5. G-CSF is administered SC twice daily beginning 6 hours after completion of etoposide and carboplatin infusions and continuing until blood counts recover. G-CSF is held on the morning of PBSC transplantation and restarted beginning 6 hours after completion of PBSC transplantation. Treatment continues every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with insufficient PBSC for the second course receive PBSC combined with ABM. Patients with insufficient PBSC for the third course receive ABM.
During the second part, cohorts of 3-6 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity.
After completion of parts A and B, some patients may undergo resection of residual masses. | Extragonadal Germ Cell Tumor Ovarian Cancer Testicular Germ Cell Tumor | recurrent malignant testicular germ cell tumor recurrent ovarian germ cell tumor extragonadal germ cell tumor | null | 1 | arm 1: The design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support. | [
0
] | 6 | [
2,
0,
0,
0,
0,
3
] | intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None | intervention 1: filgrastim intervention 2: carboplatin intervention 3: etoposide intervention 4: ifosfamide intervention 5: paclitaxel intervention 6: peripheral blood stem cell transplantation | 1 | New York | New York | United States | -74.00597 | 40.71427 | 108 | 0 | 0 | 0 | NCT00002558 | 1COMPLETED | 2009-04-01 | 1994-01-01 | Memorial Sloan Kettering Cancer Center | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 16 | RANDOMIZED | CROSSOVER | 0TREATMENT | 3TRIPLE | false | 0ALL | null | Objective: To determine if the calcium channel blockers, amlodipine can augment the effect of botulinum toxin injections in the treatment of focal dystonia.
Study Population: 20 patients with cervical dystonia
Design: Double-bind, placebo-controlled clinical trail.
Outcome measures: For patients: dystonia rating scales (Twistrs, Fahn-Marsden dystonia scale, NINDS subjective patient rating scale), and hand grip strength. For healthy volunteers: Amplitude of EDB MEP. | Objective: To determine if the calcium channel blocker, amlodipine can augment the effect of botulinum toxin injections in the treatment of focal dystonia.
Study Population: 20 patients with cervical dystonia
Design: Double-bind, placebo-controlled clinical trail.
Outcome measures: dystonia rating scales (TWISTRS) | Focal Dystonia | Writer's Cramp Calcium Channel Antagonists Torticollis Chemodenervation | null | 1 | arm 1: cervical dsytonia patinets | [
0
] | 1 | [
0
] | intervention 1: None | intervention 1: Amlodipine plus Botulinum toxin | 1 | Bethesda | Maryland | United States | -77.10026 | 38.98067 | 32 | 0 | 0 | 0 | NCT00015457 | 1COMPLETED | 2009-04-01 | 2001-04-01 | National Institute of Neurological Disorders and Stroke (NINDS) | 0NIH | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 36 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | This study will evaluate the safety and effectiveness of combination therapy with peginterferon alfa-2b and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. In studies of patients with hepatitis C alone, interferon alfa-2b plus ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon alfa-2b is a compound that results from attaching a polyethylene glycol molecule to interferon alfa-2b. This compound stays in the blood longer than unmodified interferon alfa-2b, causing a higher blood concentration and thus maintaining activity against the hepatitis C virus.
HIV-infected patients 21 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2 1/2-year study. Candidates will be screened with blood and urine tests and possibly a liver biopsy, if a recent one is not available. The liver biopsy is done to determine the severity of liver disease. For this test, patients are admitted to the NIH Clinical Center for 1 to 2 days. A sedative is injected into an arm vein, the skin in the area over the biopsy site is numbed with a local anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. A chest X-ray, electrocardiogram (EKG) and liver ultrasound are also done. Within 4 weeks of the screening tests, candidates who appear eligible for the study will have a physical examination, medical history and repeat blood tests. Women who can become pregnant will have serial pregnancy tests throughout the study.
Patients who meet the study criteria and decide to participate will begin treatment with weekly injections under the skin of peginterferon alfa-2b and take ribavirin pills twice a day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Clinic visits will be scheduled as follows:
* Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV.
* Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56 and 64 - Blood and urine tests will be done to determine the side effects of treatment and its effect on the HCV infection.
* Week 48 or end of treatment - Treatment will stop after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients will return to the clinic for a routine test. | Hepatitis C infection occurs in one-third of all HIV-infected individuals. Liver disease has become more clinically significant among patients coinfected with HIV and HCV. Several studies have shown that coinfected individuals develop earlier and severe liver disease. Interferon with ribavirin has become the therapy of choice among people with non-genotype 1a. This is a pilot study to address the relationship of clinical response to combination therapy to the virologic and immunologic parameters. The study will also address the safety and efficacy of the peginterferon alfa-2b among HIV- infected individuals. The predictive ability of baseline HCV viral load, rate of decline of HCV viral load, HIV viral load and CD4 counts to the clinical response of chronic hepatitis to peginterferon and ribavirin will also be studied. Approximately sixty patients who are infected with both HIV and HCV and also have evidence of fibrosis will receive peginterferon alfa-2b and ribavirin for 48 weeks. In order to enroll sixty patients for this study, we will be screening a total of 180 patients. During the 72 weeks study these patients will be monitored for HCV viral load, and other HIV viral load and CD4 counts. Viral kinetics will also be monitored closely and the slope of second, slower phase decline of HCV viral load, which corresponds to the rate of infected cell death presumably may lead to sustained hepatitis C virologic response. The results of the study will enable us to better delineate the possible predictors of sustained response to peginterferon and ribavirin. The safety and tolerability of a combination therapy with peginterferon and ribavirin among HIV-infected individuals on antiretroviral therapy will further define the standard therapy of chronic hepatitis C in HIV-infected individuals. | Hepatitis C HIV Infections | Liver Disease Virologic Response Immune Mechanisms Cirrhosis Eradication HIV Hepatitis C | null | 1 | arm 1: Weekly Injection of peginterferon alfa-2b and weight based ribavirin (1-1.2g/day) for 48 weeks | [
0
] | 2 | [
0,
0
] | intervention 1: Weekly injections for 48 weeks of a dose of 1.5mcg/Kg per week subcutaneously intervention 2: Weight based Ribavirin dosing 1-1.2grams/day in divided (twice daily) doses for a total duration of 48 weeks. | intervention 1: Peginterferon alfa-2b intervention 2: Ribavirin | 1 | Bethesda | Maryland | United States | -77.10026 | 38.98067 | 36 | 0 | 0 | 0 | NCT00018031 | 1COMPLETED | 2009-04-01 | 2001-06-01 | National Institute of Allergy and Infectious Diseases (NIAID) | 0NIH | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 51 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | null | RATIONALE: Giving low doses of chemotherapy, such as melphalan and fludarabine, and a monoclonal antibody, such as alemtuzumab, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well fludarabine, melphalan, alemtuzumab, and peripheral stem cell transplant work in treating patients with hematologic cancer. | OBJECTIVES:
Overall survival-12 months
Overall survival-24 months
Acute Graft-versus-Host Disease Matched Related patients-up to 4 months post transplant
Acute Graft-versus-Host Disease Unrelated and Mismatched related patients- up to 4 months post transplant
Chronic Graft-versus-Host Disease Matched Related patients- up to 2 years post transplant
Chronic Graft-versus-host disease Unrelated and Mismatched related patients- up to 2 years post transplant
* OUTLINE: Patients are stratified according to donor type (HLA-matched related vs HLA-matched unrelated, single HLA-allele disparate related, or unmatched) (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06).
Patients receive a nonmyeloablative regimen comprising alemtuzumab IV over 8 hours on days -8 to -5, fludarabine IV over 30 minutes on days -8 to -4, and melphalan IV over 30 minutes on days -3 and -2. Allogeneic peripheral blood stem cells or bone marrow is infused on day 0.
Patients receive graft-versus host disease prophylaxis comprising cyclosporine IV every 12 hours beginning on day -1 and continuing orally as tolerated until day 100.
Patients are followed every 6 weeks for 6 months, every 3 months for 6 months, every 3-6 months for 1 year, and then annually thereafter or as clinically indicated.
PROJECTED ACCRUAL: A maximum of 50 patients (25 HLA-matched related and 25 HLA-mismatched related or matched unrelated) will be accrued for this study within 2 years (HLA-mismatched related or matched unrelated donor stratum closed to accrual as of 1/11/06). | Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms | recurrent childhood acute lymphoblastic leukemia recurrent adult Hodgkin lymphoma refractory multiple myeloma stage II multiple myeloma stage III multiple myeloma recurrent childhood lymphoblastic lymphoma recurrent childhood acute myeloid leukemia recurrent adult acute myeloid leukemia recurrent adult acute lymphoblastic leukemia relapsing chronic myelogenous leukemia refractory chronic lymphocytic leukemia recurrent/refractory childhood Hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse large cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent adult Burkitt lymphoma previously treated myelodysplastic syndromes recurrent childhood small noncleaved cell lymphoma recurrent childhood large cell lymphoma recurrent mantle cell lymphoma Waldenström macroglobulinemia childhood chronic myelogenous leukemia atypical chronic myeloid leukemia, BCR-ABL1 negative myelodysplastic/myeloproliferative neoplasm, unclassifiable recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma adult acute myeloid leukemia with 11q23 (MLL) abnormalities childhood myelodysplastic syndromes | null | 1 | arm 1: This is a stratified single-armed phase II study designed to investigate the safety and efficacy of hematopoietic cell allografts administered after nonmyeloablative cytoreduction. | [
0
] | 6 | [
2,
0,
0,
0,
3,
3
] | intervention 1: Consenting individuals will receive pretransplant immunosuppressive cytoreduction, which will consist of 4 days of Campath-1H, 5 days of fludarabine, and two days of melphalan. All therapy should be completed approximately 24-36 hours before administration of the primary allograft.
Campath-1H (20mg/dose/day) will be administered for each of four days from day -8 to day -5, inclusive. Each dose will be infused intravenously over 8 hours. intervention 2: Patients will be treated with Cyclosporine as prophylaxis against GvHD. Cyclosporine will be initiated at least 1 day prior to transplant at a dose of 1.5 mg / kg IV q12h (3 mg / kg / day = total daily dose). Dose will thereafter be adjusted to maintain a trough serum level of 200-300 ng /ml. Cyclosporine will be administered intravenously until the patient tolerates full alimentation, at which time conversion to oral dosing to sustain therapeutic levels will be initiated according to standard BMT service guidelines. intervention 3: Fludarabine, 25mg/m2/d will be administered for each of five days from day -8 to day -4, inclusive. Each dose will be infused intravenously over 30 minutes. intervention 4: Melphalan will be administered intravenously over 30 minutes on each of two days from day -3 to day -2, inclusive. The dose for recipients of HLA-matched related grafts will be 50 mg/m2/day x 2. The dose for recipients of HLA-matched unrelated and HLA-single allele disparate related or unrelated marrow or PBSC transplants will be 70 mg/m2/day x 2. intervention 5: None intervention 6: None | intervention 1: alemtuzumab intervention 2: cyclosporine intervention 3: fludarabine phosphate intervention 4: melphalan intervention 5: allogeneic bone marrow transplantation intervention 6: peripheral blood stem cell transplantation | 1 | New York | New York | United States | -74.00597 | 40.71427 | 50 | 0 | 0 | 0 | NCT00027560 | 1COMPLETED | 2009-04-01 | 2001-07-01 | Memorial Sloan Kettering Cancer Center | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 32 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | true | RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bevacizumab with docetaxel may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying bevacizumab and docetaxel to see how well they work compared to bevacizumab alone in treating patients with metastatic pancreatic cancer. | OBJECTIVES:
* Determine the progression-free survival of patients with previously treated metastatic pancreatic adenocarcinoma treated with bevacizumab with or without docetaxel.
* Determine the objective response rate and overall survival of patients treated with these regimens.
* Determine the incidence of thromboembolic events in patients treated with these regimens.
OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and docetaxel IV over 1 hour on days 1, 8, and 15.
* Arm II: Patients receive bevacizumab as in arm I. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 46 patients (23 per treatment arm) will be accrued for this study. | Pancreatic Cancer | adenocarcinoma of the pancreas recurrent pancreatic cancer stage IV pancreatic cancer | null | 2 | arm 1: bevacizumab 10 mg/kg by intravenous infusion over 30-90 minutes once every 2 weeks until disease progression, unacceptable toxicity or patient preference. arm 2: rhuMAB-VEGF,bevacizumab: 10 mg/kg by intravenous infusion over 30-90 minutes once every 2 weeks docetaxel, Taxotere: 35 mg/m2 given intravenously over 1 hour on days 1, 8, and 15 of each 28 day cycle. Treatment continued until evidence of disease progression, unacceptable toxicity, or patient preference. | [
0,
0
] | 2 | [
0,
0
] | intervention 1: None intervention 2: None | intervention 1: rhuMAB-VEGF intervention 2: docetaxel | 1 | Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238 | 32 | 0 | 0 | 0 | NCT00066677 | 6TERMINATED | 2009-04-01 | 2003-10-01 | Fox Chase Cancer Center | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 46 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 2MALE | false | BAY 43-9006 (Sorafenib) is an experimental cancer drug produced by Bayer Health Care Corporation. It represents a new class of anticancer agents known as bi-aryl ureas. This study will investigate its effect on prostate cancer and its side effects. Researchers expect to enroll a maximum of 46 men with prostate cancer for this study. The duration of the study will depend on its results.
Before beginning to take the drug, patients will be admitted to the hospital for 2 days, have a medical examination and give blood samples, and have a tumor or bone marrow biopsy. On the first day of the study, patients will begin taking the drug as 2 tablets twice daily, morning and evening. Blood will be taken throughout the day to determine the drug's level in the bloodstream.
Patients will be discharged from the hospital on the second day, and will continue to take the drug twice daily until instructed to stop. During each of the first 4 weeks, patients will be required to have their blood pressure checked. At the end of the first 4 weeks, patients will have a physical examination and blood tests, as well as a second tumor or bone marrow biopsy.
After the first 4 weeks, patients will continue with their drug regimen. At the end of each 4-week cycle, patients will have a physical examination and blood tests. Patients will also have x-Rays, computed tomography (CT) scans, and/or magnetic resonance imaging (MRIs) at every other 4-week examination or as required. Patients will be asked to keep a diary recording the time and amount of their medication for this study. | BAY 43-9006 (Sorafenib) is a potent inhibitor of wild-type and mutant b-Raf and c-Raf kinase isoforms in vitro. In addition, this agent also inhibits p38, c-kit, vascular endothelial growth factor receptor 2 (VEGFR-2) and platelet-derived growth factor receptor beta (PDGFR-beta) affecting tumor growth as well as possibly promoting apoptosis by events downstream of c-Raf. At this time, over 500 patients have been treated with this drug with tolerable side effects.
The primary objective of this study is to determine if BAY 43-9006 (Sorafenib) is associated with a 50% 4 month probability of progression free survival in patients with metastatic androgen independent prostate cancer (AIPC) as determined by clinical, radiographic, and prostatic specific antigen (PSA) criteria.
The secondary objective of this study will be demonstration of biologic effect by the drug in the patient and on the tumor (when possible). Correlative studies will be conducted on serially obtained tissue biopsies, bone marrow biopsies, and white blood cell collections. These laboratory correlates will include elucidation of activation of components of the Raf-extracellular-signal regulated kinase (ERK)-methyl ethyl ketone (MEK) and angiogenesis pathways using protein microarray technologies developed by the National Cancer Institute (NCI)/Food and Drug Administration (FDA) clinical proteomics program.
Per Amendment D, a secondary objective of this study will also be to determine the time to progression measured by clinical and radiographic criteria. The 22 patients treated on the first stage of this protocol will be retrospectively evaluated with respect to this secondary endpoint possible. Please refer to the statistics section for further details.
The combination of correlated clinical and laboratory endpoints with emphasis on molecular signaling will provide new information on the anti-tumor effects helping to characterize its role in the treatment of androgen independent prostate cancer (AIPC). | Prostate Cancer | Hormone-Refractory Proteomics Angiogenesis VEGFR Prostate Cancer Metastatic Prostate Cancer | Prot_000.pdf:
1
NCI Protocol #:
CC Protocol #: 04-C-0262 (Version I)
CTEP # 6594
A Phase II Study of BAY 43-9006 (Sorafenib) in Metastatic, Androgen-Independent Prostate Cancer
Principal Investigator:
William L. Dahut, M.D., MOB/CCR/NCI
Protocol chairperson:
William L. Dahut, M.D., MOB/CCR/NCI
Co-Investigators:
Elise C. Kohn, M.D., MOB/CCR/NCI
William D. Figg, Pharm.D., MPS/CTB/CCR/NCI
James Gulley, M.D.-Ph.D., LTIB/CCR/NCI
Philip M. Arlen, M.D., LTIB/CCR/NCI
Howard Parnes, M.D., DCP/PUCR/NCI
David Kohler, Pharm.D., PD/CCR/NIH
Peter Pinto, M.D., UOB/CCR/NCI
Statistician:
Seth M. Steinberg, Ph.D., BDMS/CCR/NCI
Research Nurses:
Lea Latham, B.S.N.-R.N., MOB/CCR/NCI
Study Conducted by:
Genitourinary/Gynecologic Malignancies Clinic
Medical Oncology Branch
National Cancer Institute
Clinical Center (Bldg 10)
National Institutes of Health
Bethesda, MD 20892
Drug Monitor:
John Wright, M.D.-Ph.D., CTEP/CCR/NCI
Drug Sponsor:
CTEP
NCI Supplied Agent:
BAY 43-9006 (NSC724772)
Protocol Version Date: 11/18/2008
BAY43-9006 IND #:
38583
2
Prior to Day 0
Baseline CT Scan (chest, abdomen, pelvis)
Baseline bone scan
Baseline electrocardiogram (within 30 days of enrollment)
Baseline PSA
Baseline laboratory studies (chemistry, blood profile)
H&P
Pathologic confirmation
Tumor biopsy and/or bone marrow biopsy and aspiration
C1D1-C1D28
Begin BAY 43-9006 400 mg bid
Begin PK studies
C2D1
Return to Clinic
H&P
PSA #2
Tumor biopsy and/or bone marrow biopsy and aspiration #2 prior
Start cycle 2 day 1 BAY 43-9006
C2D1-C2D28
Continue BAY 43-9006 400 mg bid
C3D1 prior to therapy
Return to clinic
Restaging CT Scan (Chest/Abdomen/Pelvis)
Restaging Bone scan
PSA #3
If no evidence of progressive disease, begin C3D1
3
PRÈCIS
BAY 43-9006 (sorafenib) is a potent inhibitor of wild-type and mutant b-Raf and c-Raf kinase isoforms in
vitro. In addition, this agent also inhibits p38, c-kit, VEGFR-2 and PDGFR-E affecting tumor growth as well
as possibly promoting apoptosis by events downstream of c-Raf. At this time, over 500 patients have
been treated with this drug with tolerable side effects.
The primary objective of this study is to determine if BAY 43-9006 is associated with a 50% 4 month
probability of progression free survival in patients with metastatic AIPC as determined by clinical,
radiographic, and PSA criteria.
The secondary objective of this study will be demonstration of biologic effect by the drug in the patient and
on the tumor (when possible). Correlative studies will be conducted on serially obtained tissue biopsies,
bone marrow biopsies, and white blood cell collections. These laboratory correlates will include
elucidation of activation of components of the Raf-ERK-MEK and angiogenesis pathways using protein
microarray technologies developed by the NCI/FDA clinical proteomics program.
Per Amendment D, a secondary objective of this study will also be to determine the time to progression
measured by clinical and radiographic criteria. The 22 patients treated on the first stage of this protocol will
be retrospectively evaluated with respect to this secondary endpoint if possible. Please refer to the
statistics section for further details.
The combination of correlated clinical and laboratory endpoints with emphasis on molecular signaling will
provide new information on the anti-tumor effects helping to characterize its role in the treatment of AIPC.
4
TABLE OF CONTENTS
SCHEMA......................................................................................................................................................................2
PRÈCIS.........................................................................................................................................................................3
TABLE OF CONTENTS ……………………………………………………………………………………………..4
1.
OBJECTIVES…………………………………………………………………………………………….….6
2.
BACKGROUND………………………………………………………………………………………….….6
2.1
ANDROGEN-INDEPENDENT PROSTATE CANCER (AIPC)...................................................................................6
2.2
BAY 43-9006 (SORAFENIB).............................................................................................................................6
TUMOR MODEL……………………………………………………………………………………………………10
2.3
RATIONALE....................................................................................................................................................11
3.
PATIENT SELECTION……………………………………………………………………………...........11
3.1
ELIGIBILITY CRITERIA.................................................................................................................................11
3.2
EXCLUSION CRITERIA ..................................................................................................................................12
3.3
INCLUSION OF WOMEN AND MINORITIES....................................................................................................13
3.4
BASELINE EVALUATION................................................................................................................................13
3.5
PATIENT REGISTRATION..............................................................................................................................13
4.
TREATMENT PLAN……………………………………………………………………………...............14
4.1
BAY 43-9006 (SORAFENIB) ADMINISTRATION............................................................................................14
4.2
SUPPORTIVE CARE GUIDELINES ..................................................................................................................14
4.3
DURATION OF THERAPY...............................................................................................................................14
5.
DOSING DELAYS/DOSE MODIFICATIONS………………………………………………………….15
6.
PHARMACEUTICAL INFORMATION………………………………………………………………...16
7.
CORRELATIVE/SPECIAL STUDIES…………………………………………………………………...18
8.
STUDY CALENDAR………………………………………………………………………………………23
9.
MEASUREMENT OF EFFECT…………….……………………………………………………………24
9.1
DEFINITIONS .................................................................................................................................................24
9.2
GUIDELINES FOR EVALUATION OF MEASURABLE DISEASE........................................................................24
9.3
RESPONSE CRITERIA ....................................................................................................................................25
9.4
CONFIRMATORY MEASUREMENT/DURATION OF RESPONSE ......................................................................27
9.6
PROGRESSION-FREE SURVIVAL ...................................................................................................................28
9.7
RESPONSE REVIEW- N/A .............................................................................................................................28
10.
REGULATORY AND REPORTING
REQUIREMENTS…………….………………………………...28
10.1
EXPEDITED ADVERSE EVENT REPORTING..............................................................................................29
10.1.1
Expedited Reporting Guidelines ..........................................................................................................29
10.1.2
Expedited Adverse Event Reporting Exclusions- N/A ........................................................................30
10.1.3
Secondary AML/MDS.........................................................................................................................30
10.2
DATA REPORTING....................................................................................................................................30
10.3
CTEP MULTICENTER GUIDELINES- N/A................................................................................................30
10.4
COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT (CRADA)/CLINICAL TRIALS
AGREEMENT (CTA)................................................................................................................................................30
5
11.
STATISTICAL
CONSIDERATIONS………………………………………………………………………………………………...31
12.
HUMAN SUBJECTS PROTECTIONS…………………………………………………………………..33
13.
DATA AND SAFETY MONITORING PLAN…………………………………………………………...34
APPENDIX A………………………………………………………………………………………………...............38
APPENDIX B: NCI/FDA PROTEOMICS PROGRAM STANDARD OPERATING PROCEDURE FOR
TISSUE CORE COLLECTION- NEEDLE BIOPSY – CRYOPRESERVATION IN OCT…………………...39
FROZEN SECTION SLIDES..........................................................................................................................................40
SHIPPING SLIDES OR FROZEN TISSUE........................................................................................................................40
APPENDIX C: CYTOCHROME P450 3A4 METABOLIZED DRUGS………………………………………...41
6
1.
OBJECTIVES
1.1
Primary Objective
The primary objective of this study is to determine if BAY 43-9006 is associated with a 50% 4 month
probability of progression free survival in patients with metastatic AIPC as determined by clinical,
radiographic and PSA criteria.
1.2
Secondary Objectives
x
Measurement of overall response rate and overall survival
x
Per Amendment D, a secondary objective of this study is to determine whether BAY 43-9006,
when used to treat metastatic AIPC, is associated with 50% of patients progression free at 4
months by clinical and radiographic criteria. The 22 patients treated on the first stage of this
protocol will be retrospectively evaluated with respect to this secondary endpoint. Please refer to
the statistics section for further details.
x
Demonstration of biologic effect by BAY 43-9006 in the patient and on the tumor (when possible)
via correlative studies will be conducted on serially obtained tissue biopsies, bone marrow
biopsies, and white blood cell collections. Laboratory correlates will include elucidation of
activation of components of the Raf-ERK-MEK and angiogenesis pathways using protein
microarray technologies developed by the NCI/FDA clinical proteomics program.
x
Measurement of the pharmacokinetics of BAY 43-9006 in human patients with prostate cancer.
x
Description of the prostate specific antigen (PSA) response rate to therapy with BAY 43-9006.
2.
BACKGROUND
2.1
Androgen-Independent Prostate Cancer (AIPC)
Prostate adenocarcinoma is the most common malignancy in American men and the second leading
cause of cancer related deaths [1, 2]. According to the SEER database, 42% of patients have either
metastatic disease or will eventually progress following local therapy. Whereas androgen ablation therapy
is an effective initial modality, androgen independence and progression of disease eventually occurred in
all patients with metastatic prostate cancer [3, 4]. The utilization of second line hormonal agents is
generally associated with low response rates, and has no documented survival benefit.
Chemotherapies have been extensively evaluated in patients with metastatic androgen independent
prostate cancer (AIPC) since the 1970s. The initial studies showed low response rates and high toxicities.
Recently, however, with the development of new agents targeting prostate cancer both on the cellular and
molecular level, promising results have been emerging. The agents, including docetaxel, mitoxantrone,
estramustine, vinblastine and etoposide, either as a single agent or as a combination therapy, have
produced significant PSA responses in 30-80% of patients with median progression free survival of 3-5
months [5]. Chemotherapeutic agents also showed benefits in pain control, and/or quality of life, with
estramustine/docetaxel combination showing the most promise. In our prior trial of thalidomide in a similar
patient population, the median time to treatment failure was 2.2 months. However, the benefit in overall
survival is still unknown. There is no standard therapy for patients in this population which has been
shown to have an impact on survival. Therefore, new therapeutic modalities are needed in patients with
advanced AIPC.
2.2
BAY 43-9006 (Sorafenib)
BAY 43-9006 represents a novel class of anticancer agents known as bi-aryl ureas. It is a potent inhibitor
of wild-type and mutant b-Raf and c-Raf kinase isoforms in vitro. In addition, this agent also inhibits p38,
c-kit, VEGFR-2 and PDGFR-E affecting tumor growth as well as possibly promoting apoptosis by events
downstream of c-Raf. At this time, over 500 patients have been treated with this drug with tolerable side
effects [6].
Activation of the Ras oncogene signaling pathway is considered to be an important mechanism by which
human cancer develops. Raf kinase is a protein involved in the Ras signal transduction pathway. Ras
regulates several pathways which synergistically induce cellular transformation, including the
7
Raf/MEK/ERK cascade and the rac and rho pathways [7, 8]. In particular, Ras activates the Raf/MEK
pathway by first localizing Raf to the plasma membrane, where Raf initiates a mitogenic kinase cascade.
Activated Raf phosphorylates and activates MEK which in turn phosphorylates and activates ERK.
Activated ERK then translocates from the cytoplasm into the nucleus and modulates gene expression via
the phosphorylation of transcription factors. Thus activation of Raf kinase, via activation of Ras, is thought
to play an important role in carcinogenesis.
In particular, B-Raf, a serine/threonine kinase, has been shown to be activated in a number of human
tumor types including melanoma, ovarian and papillary thyroid carcinomas [9-15]. A survey of 43 cancer
cell lines showed that all B-Raf mutations resided in exons 11 or 15. Remarkably, 80% of these B-Raf
mutations represent a single nucleotide change of T-A at nucleotide 1796 resulting in a valine to glutamic
acid change at residue 599 (V599E, exon 15) in the CR3 domain (ATP binding and substrate recognition)
which in turn confers constitutive kinase activity [10, 11].
In Vitro Activity
The ability of BAY 43-9006 to inhibit a number of kinases was evaluated [6]. The in vitro biochemical and
cellular profile of BAY 43-9006 is summarized below:
Biochemical Assay
IC50 (μM)
c-Raf b
0.002/0.006
b-Raf wild-type
0.025
b-Raf V599E mutant
0.038
VEGFR-2 (human)
0.090
VEGFR-2 (murine)
0.006
VEGFR-3 (murine)
0.010
PDGFR-ȕ (murine)
0.028
Flt-3
0.058
c-KIT
0.068
FGFR-1
0.580
p38Į
0.038
Cellular Mechanismc
IC50 (μM)
MDA-MB-231 MEK phosphorylation (Human
Breast)
0.04
BxPC-3 MEK phosphorylation (Human
Pancreatic)
1.00
LOX ERK phosphorylation (Human Melanoma)
0.80
b-Raf ER MEK activation (Human Chimera,
3T3 cells)
2.30
VEGFR-2 phosphorylation (Human, 3T3 cells)
0.03
VEGFR-3 phosphorylation (Mouse, 293 cells)
0.10
PDGFR-ȕ phosphorylation (Human, AoSMC)d
0.02
Cellular Proliferation
IC50 (μM)
MDA-MB-231 (10% FCS)e
2.60
MDA-MB-231 (0.1% FCS)
0.10
VEGF-HUVEC (2.0% FCS)f
3.00
8
PDGFR-ȕ AoSMCd (0.1% BSA)g
0.23
a Recombinant enzyme assay
b Raf kinase activated with Lck (truncated/full length c-Raf)
c Mechanistic cellular assays all performed in 0.1% BSA
d Human aortic smooth muscle cells
e Fetal calf serum
f Human umbilical vein endothelial cells
g Bovine serum albumin
In vitro kinase assays demonstrated that BAY 43-9006 is a potent inhibitor of wildtype and mutant (V599E)
B-Raf and c-Raf Kinase isoforms in vitro [6]. In addition, BAY 43-9006 did not inhibit human EGFR or
Her2 kinases at 10 PM. Nor were PKC-Į, PKC-ȕ, PKC-Ȗ, and PKA (rat, rabbit and bovine sources) kinase
activity inhibited in vitro. BAY 43-9006 demonstrated an IC50 of 780 nM against p59 (bovine) Fyn kinase
(Src family of protein tyrosine kinases). In non-kinase targets BAY 43-9006 had moderate potency against
the adenosine A3, dopamine D1, and muscarinic M3 receptors with IC50 of 1.6 PM, 2.0 PM, and 3.1 PM,
respectively. BAY 43-9006 did not inhibit MEK-1, ERK-1, EGFR, HER2/neu, c-met, PKA, PKB, Cdk-
1/cyclin B, pim-1, GSK 3-b, CK-2, PKC-Į (r), PKC-ȕ (r), PKC-Ȗ at concentrations as high as 10 μM. In
summary, BAY 43-9006 showed 100-fold more selectivity for Raf kinase relative to other target proteins.
BAY 43-9006 also inhibited in vitro several receptor tyrosine kinases (RTKs) that are involved in tumor
progression; human VEGFR-2, murine VEGFR-2, murine VEGFR-3, murine PDGFR-ȕ, Flt-3, c-KIT, and
p38Į (MAPK family). In cellular assays, BAY 43-9006 was found to be a potent inhibitor of human and
murine VEGFR-2, murine VEGFR-3, and murine PDGFR-ȕ receptor phosphorylation [6].
VEGF and PDGF receptors are involved in the mechanism of tumor angiogenesis [16, 17]. PDGF
receptors may also play a role in patients with chronic myeloproliferative cancers [18]. Flt-3 is important in
acute myelogenous leukemia [13] and c-Kit plays a critical role in gastrointestinal stromal tumors [19].
In Vivo Activity
BAY 43-9006 has demonstrated in vivo anti-tumor efficacy as a single agent against a broad range of
human tumor xenografts as summarized in the following table. The models evaluated include HCT-116
and DLD-1 colon tumor xenografts, MX-1 mammary tumor xenograft, NCI-H460 and A549 NSCLC
xenografts, MiaPaCa-2 pancreatic tumor xenografts, and SK-OV-3 ovarian tumor xenografts. In this table,
compound efficacy is expressed as percent tumor growth inhibition (TGI) and is calculated as ((1-(T/C))
*100, where T and C represent the mean tumor size in the Treated and Control groups respectively at the
first measurement after the end of treatment.
9
BAY 43-9006 Demonstrates Broad Spectrum Anti-Tumor Efficacy in
Preclinical Xenograft Models
Tumor Type
Model
Dose (mg/kg/dose
free base equiv.)1
Percent TGI
((1-(T/C))*100)
Colon
HCT-116
10
30
100
45
64
68
Colon
DLD-1
15
30
60
31
66
75
NSCLC
NCI-H460
10
30
27
56
NSCLC
A549
30
60
60
68
Mammary
MX-1
30
60
51
67
Pancreatic
Mia-PaCa-2
10
30
100
45
66
73
Ovarian
SK-OV-3
10
30
100
58
64
81
1 Compound dosed as BAY 43-9006 or equivalent
dose levels of tosylate salt, BAY 54-9085
The majority of the initial anti-tumor efficacy evaluations in vivo were conducted in the HCT116 colon
tumor model since the tumorigenicity of this cell line was previously shown to be dependent on K-Ras
activation. Additional studies indicated that prolonged anti-tumor efficacy could be attained by extending
the duration of treatment and that, in this tumor model, BAY 43-9006 was able to arrest tumor growth even
if therapy was initiated against a substantially greater tumor burden.
BAY 43-9006 also showed significant oral activity against two additional human tumor xenograft models
that contain K-Ras mutations: MiaPaCa-2 pancreatic carcinoma and H460 non-small cell lung carcinoma.
The anti-tumor efficacy of BAY 43-9006 was also evaluated against the human SKOV-3 ovarian tumor cell
line that contains a wild-type Ras but over-expresses both the EGF and Her2 growth factor receptors.
These receptors also signal through the Ras/Raf/MEK pathway.
In human tumor xenografts, MDA-MB-231 (breast) and Colo-205 (colon), there was a dramatic reduction
of tumor neo-vascularization [6]. Recent data also indicated that inhibition of c-Raf may promote cell
death in endothelial cells as a downstream event of VEGFR-2 stimulation [20].
Taken together, data suggests that BAY 43-9006 may be of therapeutic value not only in human tumors
containing Ras gene mutations, but also in tumors over-expressing growth factor receptors in the
Ras/Raf/MEK pathway, and by inhibiting tumor angiogenesis or neo-vascularization through inhibition of
VEGFR-2, VEGFR-3, and/or PDGFR-ȕ.
10
The ability of BAY 43-9006 (or its tosylate salt, BAY 54-9085) to be combined with paclitaxel, irinotecan,
gemcitabine, or cisplatin was evaluated in preclinical in vivo models. In these studies, the focus was to
evaluate if the co-administration of BAY 43-9006 would adversely affect the tolerance or anti-tumor
efficacy of the ‘standard of care’ agent. The general health of mice was monitored and mortality was
recorded daily. Tumor dimensions and body weights were recorded twice a week starting with the first day
of treatment. Treatments producing greater than 20% lethality and/or 20% net body weight loss were
considered ‘toxic’. The results of these combinability analyses are summarized below:
Combinability of Concurrent Treatment with BAY 43-9006 and
Clinically Established Agents
Combination
Agent
Tumor Model
Combinability
Y/N
Paclitaxel
NCI-H460 NSCLC
MX-1 Mammary
Yes
Yes
Irinotecan
DLD-1 Colon
Yes
Gemcitabine
MiaPaCa-2 Pancreatic
Yes
Cisplatin
NCI-H23 NSCLC
Yes
BAY 43-9006 can be safely combined with a variety of standard cytotoxic cancer chemotherapy agents,
including paclitaxel, irinotecan, gemcitabine and cisplatin with no significant increase in the toxicity
associated with those agents and without diminishing their anti-tumor efficacy in preclinical models.
Clinical Experience
BAY 43-9006 has been evaluated in multiple Phase 1 and Phase 2 studies in a variety of tumor types. To
date, over 500 patients have been treated with single agent BAY 43-9006. The Phase 1 single agent
clinical plan has focused on characterizing the safety and pharmacokinetic profile BAY 43-9006 in several
different dosing regimens. All Phase 1 patients had a variety of advanced refractory solid tumors, and
some of the patients stayed on trial for more than one year. Four different regimens have been tested:
continuous treatment, 4 weeks on/ 1 week off, 3 weeks on /1 week off, and 1 week on/ 1 week off.
Patients have received doses ranging from 50 mg once weekly to 1600 mg daily of BAY 43-9006 on
intermittent and continuous schedules. The 800 mg bid continuous administration cohort has exceeded
maximum tolerated dose (MTD) in all tested schedules. The 600 mg bid cohort exceeded the MTD in all
but the less dose intensive regimen of 1 week on / 1 week off. The most frequent drug-related adverse
events were hand-foot skin reaction, dermatitis, rash, fatigue, anorexia and diarrhea. The most common
dose limiting toxicities (DLTs) in the phase I trials were hand-foot syndrome, fatigue, pain, diarrhea,
elevated alkaline phosphatase, and abdominal pain/cramping. DLTs were rarely attriubuted to the
following: hypertension weight loss, anorexia, pancreatitis, elevated amylase and lipase without
pancreatitis,
There was an increase in the number of serious adverse events, discontinuations due to adverse events,
and a number of skin toxicities at the higher dose levels 600 mg bid. Therefore, 400 mg bid was selected
as the recommended dose for Phase 2.
Currently, the Phase 2 program includes studies designed to explore anti-tumor efficacy in certain tumor
types and to gain additional experience with pharmacokinetics and safety. Thus far, Phase 2 studies have
enrolled over 300 patients with a variety of tumor types including colorectal, renal cell, hepatocellular,
pancreatic, and thyroid cancer and melanoma as well as several less common tumors.
In general, available information from the ongoing Phase 2 studies reveal toxicities that are similar to the
Phase 1 data. Again, the five most frequent drug-related toxicities observed include hand-foot skin
11
reaction, rash, anorexia, diarrhea, and fatigue. When all available data from the various studies/schedules
are combined, the incidence of greater than grade 3 treatment emergent skin toxicity (e.g. hand-foot
syndrome and “dermatology/skin reaction”) for an initial dose of 400 mg bid and 600 mg bid, was 0% and
30%, respectively. Anti-tumor activity was observed in both Phase 1 and 2 studies.
Pharmacokinetics
Pharmacokinetic studies in humans shows that BAY 43-9006 undergoes metabolism to a few primary
metabolites, some of which may be active [6]. No data are available at this writing to describe the
pharmacokinetics of repetitive dosing of BAY 43-9006 in patients. However, up to 36 hours after a single
dose, BAY 43-9006 continues to be the predominant species detected. In vitro liver microsomal
degradation studies data indicate that BAY 43-90006 is primarily metabolized by CYP 3A4. Ongoing
studies are being pursued by the Sponsor to evaluate drug-drug interaction potential of BAY 43-9006 with
agents that alter function of CYP2C19, CYP2D6, and CYP3A4. Moderate fat meals do not affect
bioavailability of BAY 43-9006; it is in fact recommended to be administered with or around meals.
Approximately 19% of dose is excreted in urine and 76% in feces.
2.3
Rationale
Specific to prostatic adenocarcinomas, strong epithelial staining for Ras oncoproteins has been seen with
a significant difference in expression levels between normal and tumor cells. Furthermore, an inverse
correlation between Ras positivity and degree of differentiation and survival has been reported [21, 22].
Such findings suggest that functional activation of wild-type Ras might contribute to prostate
tumorigenesis.
Bakin and colleagues [23, 24] demonstrated that manipulation of Ras-related signaling affected sensitivity
to hormonal interventions in vitro. This pathway is involved in the mediation of responses to a number of
growth factors as well angiogenic factors. More recently, Fu and colleagues have been able to
demonstrate that when Raf kinase inhibitor protein (RKIP) is transfected into C4-2B cells (malignant
prostatic rat epithelial cells derived from LNCaP cells with a metastatic phenotype), invasion was
decreased and development of lung metastases in animal models was no longer seen suggesting that this
pathway is associated with suppression of tumor metastases [25].
In addition to activity on Raf-associated signaling, BAY 43-9006 has been described to affect human
VEGFR-2, murine VEGFR-2, murine VEGFR-3, murine PDGFR-ȕ, Flt-3, c-KIT, and p38Į (MAPK family).
Multiple reports in the available literature report VEGF expression in most prostatic carcinomas [26] and
expression of VEGFR may relate to migratory and invasive ability. Furthermore, in vitro models have
suggested that activation of p38-MAPK active pro-apoptotic pathway activity in prostate cancer [27].
While the remainder of the targets listed above have not been well characterized in prostate cancer, their
impact on the angiogenic cascade is of interest in prostate cancer as several groups have proposed
manipulation of angiogenic signaling as a therapeutic target [28].
Given the potential role of the Ras-Raf pathway in metastatic prostate cancer in addition to the known in
vivo and in vitro activity of the agent, we propose the execution of a phase II trial to measure the efficacy
of this compound in preventing progression of AIPC. At this time little data exists for this agent in AIPC.
This study represents the first formal inquiry into this matter.
3.
PATIENT SELECTION
3.1
Eligibility Criteria
3.1.1
Patients must have histopathological confirmation of prostate cancer by the Laboratory of
Pathology of the NCI or Pathology Department of the National Naval Medical Center prior to entering this
study. Patients whose pathology specimens are no longer available may be enrolled in the trial if the
patient has a clinical course consistent with prostate cancer and available documentation from an outside
pathology laboratory of the diagnosis. In cases where original tissue blocks or archival biopsy material is
available, all efforts should be made to have the material forwarded to the research team for use in
correlative studies.
3.1.2
Patients must have metastatic progressive androgen-independent prostate cancer. There must
12
be radiographic evidence of disease after primary treatment with either surgery or radiotherapy
that has continued to progress despite hormonal agents. Progression requires that a measurable
lesion is expanding, new lesions have appeared, and/or that PSA is continuing to rise on
successive measurements. Patients on flutamide must have disease progression at least 4 weeks
after withdrawal. Patients on bicalutamide or nilutamide must have progression at least 6 weeks
after withdrawal.
3.1.3
Patients may have had no more than 1 previous cytoxic chemotherapeutic line.
3.1.4
Because no dosing or adverse event data are currently available on the use of BAY 43-9006 in
patients <18 years of age, children are excluded from this study.
3.1.5
Patients must have a life expectancy of more than 3 months.
3.1.6
Patients must have a performance status of 0 to 2 according to the ECOG criteria.
3.1.7
Patient must have adequate organ function as defined below:
Leukocytes
>3,000/ȝl
absolute neutrophil count
>1,500/ȝl
Platelets
>100,000/ȝl
total bilirubin
1.5 X institutional upper limits of normal
AST(SGOT) and ALT(SGPT)
<2.5 X institutional upper limit of normal
creatinine
OR
Creatinine clearance
1.5 X institutional upper limits of normal
>60 mL/min/1.73 m2 for patients with creatinine
levels above institutional normal.
3.1.8
Patients must have recovered from any acute toxicity related to prior therapy, including surgery.
Toxicity should be grade 1 or returned to baseline.
3.1.9
Hormonal profile: all patients who have not undergone bilateral surgical castration must continue
suppression of testosterone production by appropriate usage of GnRH agonists.
3.1.10 Patients must not have other invasive malignancies (within the past two years with the exception
of non-melanoma skin cancers or non-invasive bladder cancer).
3.1.11 Patients must be able to understand and sign an informed consent form.
3.1.12 Concurrent use of bisphosphonates will be allowed for patients with known bone metastases
3.1.13 Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin) , NSAIDs,
and other maintenance medications prior to study entry will be allowed to continue their supportive
therapies.
3.1.14 The effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose
are unknown. For this reason and because Raf-kinase inhibitors are known to be teratogenic, men must
agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) prior to
study entry and for the duration of study participation.
3.2
Exclusion Criteria
3.2.1
Patients who have had chemotherapy or radiotherapy (including radioisotopes) within 4 weeks (6
weeks for nitrosoureas or mitomycin C; >3 months for suramin) prior to entering the study or those who
have not recovered from adverse events due to agents administered more than 4 weeks earlier.
3.2.2
Patients may not be receiving any other investigational agents.
3.2.3
Patients with known brain metastases are excluded from this clinical trial because of their poor
13
prognosis and because they often develop progressive neurologic dysfunction that would confound the
evaluation of neurologic and other adverse events.
3.2.4
History of allergic reactions attributed to compounds of similar chemical or biologic composition to
BAY 43-9006
3.2.5
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.
3.2.6
Hypertension as defined by systolic blood pressure in excess of 170 mmHg or diastolic pressure
in excess of 100 mmHg. Patients with a history of hypertension that is well controlled on medication will
not be excluded. Patients may not be on either verapamil or diltiazem while on study. Use of calcium
channel blocker should be discouraged.
3.2.7
Patients with immune deficiency are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral
therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006.
Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when
indicated.
3.2.8
History of bleeding diathesis
3.2.9
Patients on therapeutic anticoagulation are at increased risk from bleeding while on BAY 43-9006.
Prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed
provided that the requirements for PT, INR or PTT are met: PT < 1.1 x institutional upper limit of normal;
INR < 1.1; PTT within the institutional limits of normal. These requirements will only be made upon those
patients on warfarin.
3.3
Inclusion of Women and Minorities
Men of all races and ethnic groups are eligible for this trial. Women are excluded by the nature of the
disease.
3.4
Baseline evaluation
3.4.1
Imaging Studies (Baseline- obtained within one month prior to enrollment): Technetium-99 Bone
Scintigraphy, Chest X-ray, CT scan of chest, abdomen and pelvis
3.4.2
Laboratory Evaluation (Baseline- obtained within 16 days prior to enrollment)
3.4.2.1 Hematological Profile: CBC with differential and platelet count, PT, aPTT, fibrinogen
3.4.2.2 Biochemical Profile: electrolytes, BUN, creatinine, AST, ALT, total bilirubin, calcium,
phosphorus, albumin, magnesium, uric acid, C-reaction protein, albumin, amylase, lipase,
testosterone level.
3.4.2.3 Tumor Marker Profile: PSA (baseline within 7 days prior to enrollment), acid phosphatase
(if PSA <4 ng/mL, for research purposes only)
3.4.2.4 Electrocardiogram (performed within 30 days prior to enrollment); Patients with a history
of myocardial infarction or cardiac arrhythmias will undergo evaluation by cardiology.
3.5
Patient Registration
3.5.1
Authorized physicians or designees must telephone information concerning an eligible candidate
to the Orkand personnel (Orkand is the current data management contract company for the Center for
Cancer Research of the NCI) by fax at (301) 480-0757 between the hours of 8:30am and 5:00pm, Monday
through Friday.
3.5.2
At the time of enrollment, eligibility criteria will be queried. Protocol specific eligibility checklist will
be developed by the Orkand staff and reviewed by the principal investigator.
14
3.5.3
The Orkand personnel are to be called at the time any patient is taken off the study
4.
TREATMENT PLAN
This study will be executed in a two-stage optimal design as described by Simon et al [29]. In the first
stage, 22 patients will be enrolled and evaluated for progression. If 8 patients show disease stability
beyond 4 months accrual will continue to the full 46 patients. If among the first 22 patients, 7 or fewer are
able to be progression free at the 4 month evaluation, then no further patients will be enrolled and the
study will close to accrual. Should 18 or more patients remain progression free at 4 months, BAY 43-9006
will be considered worthy of further development in clinical trials. If 8-17 patients are progression free at 4
months, the study set will be considered insufficient. Under the null hypothesis (30% progression free at 4
months), the probability of being able to stop accrual after 22 patients have been evaluated at 4 months is
67%.
The study was originally designed to have a two-stage design with 22 and then up to a total of 46 patients
evaluating progression using PSA criteria. The results from the first stage were inadequate to justify
accrual to the second stage. However, per amendment D, waiver of the stopping rule is requested to allow
for accrual to the second stage.
4.1
BAY 43-9006 (Sorafenib) Administration
At the outset of the study, the patient will be admitted to the inpatient service for a period of approximately
24 hours to complete research studies including biopsies and PK measurements. Otherwise, treatment
will be administered on an outpatient basis. Reported adverse events and potential risks are described in
Section 6. Appropriate dose modifications for BAY 43-9006 are described in Section 5. No investigational
or commercial agents or therapies other than those described below may be administered with the intent
to treat the patient’s malignancy.
BAY 43-9006 is supplied as 200-mg tablets and is administered orally twice a day. Patients are to swallow
the tablets whole with approximately 250 ml (8 oz.) of water, each morning and evening (i.e., 12-hourly).
Tablets may be taken with or without food. BAY 43-9006 will be given as self-administered oral doses of
400 mg bid continuously throughout the 28 day cycle. Patients will be asked to administer the drug at
approximately 08:00 and 20:00 hours. Patients will be asked to maintain a diary to document
consumption of BAY 43-9006 as out lined in section 6 and 12.6.7.
Patients will be required to have weekly blood pressure monitoring for the first 4 weeks of the study at a
healthcare facility given the risk of hypertension from BAY 43-9006. This will be logged into the patient’s
study diary during the first 4 weeks of treatment.
4.2
Supportive Care Guidelines
4.2.1
No premedications will be used with the initiation of therapy.
4.2.2
Nausea
Should patients develop persistent nausea, they will be given appropriate antiemetic therapy
following clinical center guidelines starting with prochlorperazine 10 mg PO/IV q8h prn.
4.2.3
Hand-Foot Syndrome
o
Treatment with topical emollients (such as Aquaphor) for symptom relief is permitted.
o
Topical and/or oral steroids or antihistamine agents may be used.
o
Vitamin B6 (pyridoxine; 50 - 150 mg orally each day) may also be used.
4.3
Duration of Therapy
In the absence of treatment delays due to adverse event(s), treatment may continue until one of the
following criteria applies:
o
Disease progression
15
o
Intercurrent illness that prevents further administration of treatment
o
Unacceptable adverse event(s)
o
Patient decides to withdraw from the study, or
o
General or specific changes in the patient’s condition render the patient
unacceptable for further treatment in the judgment of the investigator.
o
Subject death
5.
DOSING DELAYS/DOSE MODIFICATIONS
Toxicities will be described using CTCAE v3. The following adjustment will only apply if the toxicities
reported are attributed by the investigator to be related to BAY 43-9006 therapy.
For Grade 1 toxicity, treatment with BAY 43-9006 will not be interrupted. For symptoms that last more
than 7 days and have been found to be intolerable to the patient, the dose of BAY 43-9006 may be
reduced by 200 mg/day (i.e.200 mg qAM and 400 mg qPM as the initial reduction).
For Grade 2 toxicity
For nausea, vomiting and diarrhea, maintain dosing with symptomatic treatment. The dose of
BAY 43-9006 may be repeated if emesis occurs within 30 minutes of taking the tablet(s) OR all
the tablets are seen in the emesis.
For persistent nausea, vomiting or diarrhea despite symptomatic treatment that remains
unacceptable (intolerable) to the patient, reduce dose by 200 mg/day (i.e.200 mg qAM and 400
mg qPM as the initial reduction).
For other grade 2 toxicities, the dose does not need to be reduced unless side effects become
intolerable to the patient.
If patients are receiving 200 mg bid at the time of occurrence/recurrence of toxicity, change the
schedule of administration to 200 mg qd. Reductions below this dose/schedule will not be
allowed.
Patients with intolerable or limiting toxicity while taking 200 mg qd will be removed from study. .
For Grade 3 clinical toxicity, or Grade 3/Grade 4 metabolic/hematologic toxicityHold BAY 43-9006
and reevaluate the patient at least weekly until toxicity improves to Grade 1 or pre-treatment
baseline. Grade 3 metabolic toxicities which can be corrected to Grade 1 or pre-treatment
baseline within 48 hours will not necessitate a dose reduction. For Grade 4 metabolic toxicity or
Grade 3/4 hematologic toxicity the dose of BAY 43-9006 will be reduced by 200 mg/day. .
Treatment will be discontinued in patients who experience toxicity grade 3 or 4 that does not resolve
to grade 1 or baseline within 3 weeks.
If patients are receiving 200 mg bid at the time of occurrence/recurrence of toxicity, change the
schedule of administration to 200 mg qd. Reductions below this dose/schedule will not be
allowed.
Patients with intolerable or limiting toxicity while taking 200 mg qd will be removed from study.
For Grade 4 clinical toxicity
Patients who had clinical grade 4 toxicity (except pulmonary embolism without significant hypoxia
and hemodynamic instability) will be taken off study permanently.
5.1
Hypertension
Given that hypertension is one of the major toxicities that may be experienced, all patients should
have blood pressure measured and recorded weekly during the first 4 weeks and as needed,
thereafter.
Grade of Event (CTCAE v.3)
Management/ Next Dose
grade 1
No dose modification
grade 2 asymptomatic and diastolic
BP < 110 mm Hg
Begin (additional) anti-hypertensive therapy and
continue agent.
grade 2 symptomatic/ persistent
OR
diastolic BP 110 mm Hg
OR
grade 3
1. Agent should be held until symptoms resolve and
diastolic BP 100 mm Hg; treat patient with anti-
hypertensives and when BAY 43-9006 is restarted,
reduce dose level as described above*
2. If diastolic BP not controlled ( 100) on therapy,
reduce dose again**
grade 4
Discontinue protocol therapy
* May be able to resume full dose later.
** Patients requiring > 2 dose reductions should go off protocol therapy.
Current CTCAE definitions used by CTEP:
x
Grade 1: asymptomatic, transient (< 24 hours) increase by > 20 mmHg (diastolic) or to
o
>150/100 if previously WNL; intervention not indicated
x
Grade 2: recurrent or persistent (> 24 hours) or symptomatic increase by > 20 mmHg
o
(diastolic) or to > 150/100 if previously WNL; monotherapy may be indicated
x
Grade 3: requiring more than one drug or more intensive therapy than previously
x
Grade 4: life threatening (e.g. hypertensive crisis)
5.1.1 Recommended antihypertensive therapy
Patients requiring additional antihypertensive therapy while on BAY 43-9006 should be
started on a beta blocker, diuretic, angiotensin converting enzyme inhibitor (ACE-I) or an
angiotensin II receptor blocker (ARB). Doses should be advanced as needed until the
patient is unable to tolerate the antihypertensive medication due to side effects. If further
medication is required a beta-blocker should be initiated and doses advanced. Calcium
channel blockers should be avoided.
5.1.2
For severe hypertension, hypertensive urgency/emergency
BAY 43-9006 should be held and the patient should be admitted. An EKG should be
obtained and, if appropriate, cardiology should be consulted. Inpatient therapy for
hypertension should be initiated.
5.1.3
Therapy may be continued if the hypertension is successfully controlled with
additional medication. However, for hypertension that persists despite additional medical
therapy or becomes symptomatic, therapy will be held as described above. If therapy is
held for 4 weeks, the patient will be taken off of study.
5.2 GI Perforation (NOS)
If a patient experiences GI perforation while on study of any grade, patient must be taken
off the study.
6.
PHARMACEUTICAL INFORMATION
6.1 BAY 43-9006 (Sorafenib, NSC 724772, IND 38583)
6.1.1
Source: BAY 43-9006 will be supplied by the Bayer Health Care Corporation and distributed by
CTEP
16
17
6.1.2
Chemical name and identification
Chemical Name: 4–-pyridine-2 carboxylic acid methylamide-4-methylbenzensulfonate.
Other Names: BAY 54-9085 is the tosylate salt of BAY 43-9006; sorafenib
Classification: Kinase inhibitor (Raf, VEGF-R, and PDGF-R)
Mechanism of Action: The Ras/Raf signaling pathway is an important mediator of responses to
growth signals and angiogenic factors. This pathway is often aberrantly activated in human tumors
due to presence of activated Ras, mutant b-Raf, or over expression of growth factor receptors.
BAY 43-9006 is a potent inhibitor of c-Raf, and wild-type and mutant b-Raf in vitro. Additionally,
further characterization of BAY 43-9006 tosylate revealed that this agent inhibits several receptor
tyrosine kinases (RTKs) that are involved in tumor progression (VEGF-R, PDGF-R, Flt3, and c-
KIT) and p38Į, a member of the MAPK family.
Molecular Formula:
C12H16CIF3N4O3 X C7H8O3S
M.W.:
BAY 43-9006 tosylate: 637 Daltons; BAY 43-9006 (free base): 465 Daltons
Approximate Solubility: 0.19 mg/100 mL in 0.1 N HCl, 453 mg/100 mL in Ethanol, and 2971 mg/100
mL in PEG 400.
How Supplied:
BAY 43-9006 tosylate is supplied as an immediate-release film-coated, round,
and salmon color tablet containing 200 mg of the free base, BAY 43-9006, and
the
excipients
croscarmellose
sodium,
microcrystalline
cellulose,
hydroxypropylmethylcellulose, sodium lauryl sulfate, and magnesium stearate.
The film-coat consists of hydroxypropylmethyl cellulose, polyethylene glycol,
tiranium dioxide and red iron oxide. The film coating has no effect on the rate of
release of the active BAY 43-9006 tosylate.
BAY 43-9006 tosylate 200 mg tablets are supplied in bottles of 140 tablets.
Storage:
Store at controlled room temperature (15ºC – 25ºC). Storage conditions should
not exceed 25ºC.
Stability:
Stability studies with the 200 mg dosage form are ongoing. The current shelf life
is 24 months when stored at controlled room temperature.
Route of Administration: Oral
Reported Adverse Events and Potential Risks:
Body as a whole:
fatigue, flu-like syndromes, fever, arthralgia
Gastrointestinal:
diarrhea, pancreatitis, elevated amylase/lipase, abdominal
pain/cramping, nausea, flatulence, dyspepsia
Hepatic:
increased bilirubin, ALT, AST, GGT, LDH, and alkaline
phosphatase
Metabolic and Nutritional:
anorexia
Skin:
hand-foot syndrome, characterized by palmar and plantar
erythema; rash/desquamation, hypersensitivity reactions, dry
skin, alopecia, nail changes, vitiligo, itching
Cardiovascular:
cardiac arrhythmias
Other:
voice changes
The following adverse events have been reported on trials but with the relationship to BAY 43-9006 still
undetermined: arthritis, brain stem stroke, dyspnea, hypertension, increase PT and PTT, and weight loss.
Method of Administration:
BAY 43-9006 tosylate should be taken with at least 250 mL of water and
can be given without regards to meals. Food does not appear to have a
18
clear effect on BAY 43-9006 tosylate pharmacokinetics.
Potential Drug Interactions:
BAY-9006 tosylate is metabolized by the P450 CYP3A enzyme and has
been shown in preclinical studies to inhibit multiple CYP isoforms.
Therefore, it is possible that BAY-9006 tosylate may interact with drugs
that are metabolized by the P450 CYP isoenzymes or with drugs that
inhibit CYP 3A. Close monitoring is recommended for patients taking
agents with narrow therapeutic indices and metabolized by the liver,
such as warfarin, phenytoin, quinidine, carbamazepine, phenobarbital,
cyclosporine, and digoxin. Additionally, BAY-9006 tosylate is 97% to
99% protein bound; however, no drug interactions have been reported in
studies, thus far.
Availability
BAY 43-9006 is an investigational agent supplied to investigators by the Division of Cancer Treatment and
Diagnosis (DCTD), NCI.
Agent Ordering
NCI-supplied agents may be requested by the Principal Investigator (or their authorized designees) at
each participating institution. Pharmaceutical Management Branch (PMB) policy requires that the agent
be shipped directly to the institution where the patient is to be treated. PMB does not permit the transfer of
agents between institutions (unless prior approval from PMB is obtained). Completed Clinical Drug
Requests (NIH-986) should be submitted to the PMB by fax (301) 480-4612 or mailed to the
Pharmaceutical Management Branch, CTEP, DCTD, NCI, 9000 Rockville Pike, EPN Rm. 7149, Bethesda,
MD 20892.
Agent Accountability
The investigator, or a responsible party designated by the investigator, must maintain a careful record of
the inventory and disposition of all drugs received from DCTD using the NCI Drug Accountability Record
Form (DARF). BAY 43-9006, as an oral self-administered investigational agent, will be properly
accounted for, handled, and disposed in accordance with CCR Policy # Clin-1 “Policy on Documenting,
Handling and Disposing of Oral Investigational Agents that are Self-Administered by NCI CCR patients.”
The Standard Operating Procedure # Clin-1 “Standard Operating Procedure for Conducting and
Documenting Drug Accountability for Oral Investigational Agents that are Self Administered by Patients at
the CCR” identifies all activities associated with drug accountability for orally self administered
investigational agents. Study drug may be repackaged by the Clinical Center Pharmacy Dept. and
dispensed in light-resistant HDPE containers that contain up to a 28-day supply of BAY 43-9006..
Patients will be instructed to document on a study diary the daily intake of BAY 43-9006, including the time
the dose is taken, and whether or not any doses are missed. They will bring the study diary and any
unused drug to their clinic appointments. Clinic staff will (1) collect all “old” [i.e., empty bottle(s), partial
bottle(s) or full bottle(s)] of study drug; (2) perform a capsule count and record the results on the approved
CCR Pill Count Case Report Form which is to be maintained in the research record; (3) dispense the
partial and full bottle(s) of BAY 43-9006 to the patient. Unused study drug is to be returned to the
research nurse who will dispose of it according to the SOP.
7.
CORRELATIVE/SPECIAL STUDIES
7.1
Tissue analysis for molecular endpoints
Given the nature of this pharmacologic intervention, characterization of the actual biological manipulation
will be critical in understanding the biological effects seen following administration. Tissue samples will be
analyzed to achieve this goal.
The collection of correlative studies is designed to characterize a baseline molecular profile as well as a
treatment-induced molecular profile. Raf mutational analysis will allow for retrospective analysis of
responsiveness in the presence or absence of mutations. Proteomic analysis will provide profiles of
signaling pathways pre-treatment and on treatment so as to understand how this agent affects a variety of
19
important signaling cascades associated with its reported molecular targets. In particular, primary
endoints address key events in survival, proliferation, and angiogenesis which will affected either directly
or downstream of Raf or VEGFR/PDGFR targets. Pharmacokinetic anlaysis will provide insight into
dosing efficacy as it realtes to both biological activity and clinical response.
Correlative laboratory studies for this trial will be conducted in the Clinical Pharmacology Section of Dr.
William D. Figg at the NCI and by Dr. Elise C. Kohn. All patients will have leukocyte collections (by
standard buffy coat preparation) to evaluate for tumor and gene expression alterations related to drug
therapy. Patients with accessible disease will have tumor biopsies before and during treatment for
molecular analysis described below.
Tumor Biopsies
Bone Marrow
Archival Tissue
Leukocytes
Proteomic pathway
analysis
Proteomic pathway
analysis
B-Raf genomic analysis
Proteomic pathway
analysis
B-Raf mutational
screening
Cross-validation with
tumor biopsy
Cross-validation with
tumor biopsy
7.1.1
Accessible tumor biopsy
Biopsies of accessible tumors will be required prior to initiation of therapy and prior to starting
cycle 2 as described. Patients should avoid the use of aspirin or non-steroidal anti-
inflammatory drugs for 1 week prior to biopsy to ensure safety. Accessible tumors will be
defined as those masses which can be safely accessed by a core needle biopsy while posing
minimal risk to the patient. These lesions may be cutaneous or palpable or demonstrable under
CT or ultrasound guidance. Determination of accessibility and safety will be made jointly by an
investigator and a staff member from Special Procedures. Accessible tumors will be defined as
those masses which can be safely accessed by a core needle biopsy under CT or ultrasound
guidance or while posing minimal risk to the patient. Laser capture microdissection and cell
lysates will be prepared for protein microarrays with targets as identified below. Garreth Peters
(pager 104-4587-7 or 301-402-4622) or Dr. Edwin Posadas (phone 301-451-4982 pager 104-
6563) should be contacted to arrange for sample collection. Samples should be preserved in
OCT according to the NCI/FDA clinical proteomics program SOP (appendix B). Samples should
be barcoded and stored in liquid nitrogen until the time of preparation for microdissection.
Biopsy specimens will be used for tissue lysate array analysis in the proteomics laboratory (see
section 7.2) for signal pathway profiling before and during treatment as well as Raf mutation
detection via TLA.
7.1.2.
Bone marrow biopsy and aspiration
In addition to attempting to obtain tumor biopsies, attempts will be made to determine effect in
both bone marrow and in white blood cells. Bone metastases are a common event in metastatic
prostate cancer affecting about 80% of patients. In limited series, bone marrow trephines and
aspirations were shown to yield metastatic tumor cells in 75% of cases using traditional
histopathologic techniques [30]. Given the fact that patients often have bone as their sole site of
metastasis and the relative difficulty of obtaining soft tissue biopsies for direct tumor sampling,
bone marrow aspiration and biopsy may be a powerful tool in assessing biological response both
in the tumor and in the tumor microenvironment. This question will be addressed using protein
microarrays in conjunction with immunohistochemistry on these samples.
Marrow cores and aspirate collection will not be mandated, but will be requested of all patients. In
addition, given the activity of BAY 43-9006 on angiogenic pathways and receptor tyrosine kinases,
markers of angiogenesis including VEGFR and PDGFR and associated signals will be
characterized as well. These results will be compared to findings obtained for tumor biopsy
analysis to describe the correlation of these findings.
Bone marrow specimens should be obtained from the posterior iliac crest when possible.
Aspiration should precede trephine biopsy collection. A total of 2-3 ml of marrow will be aspirated
into a heparainzed syringe with no heparin remaining in the syringe at the time of collection. The
20
aspirate should be preserved in 0.5 ml aliquots stored in cyropresevation (Nunc) vials and will be
stored in the laboratory of Dr. W. Douglas Figg until processing. The samples should be
immediately frozen and stored at – 80 C until thawed for analysis. Biopsy material should be
collected by a representative of Dr. Figg’s laboratory. Garreth Peters (pager 104-4587-7 or 301-
402-3622) should be notified for sample collection.
Trephine biopsies (bone marrow core biopsies) should be immediately preserved in OCT,
barcoded, and stored in liquid nitrogen until the time of utilization.
Bone marrow biopsies will be lysed and printed on protein lysate arrays and analyzed as
described below (section 7.2).
7.1.3
Leukocyte analysis
In addition to either direct tumor or bone marrow analysis, leukocytes will be isolated by buffy coat
and lysed for correlative analysis of the Ras/Raf pathway elements, angiogenic markers, and RTK
makers using the same protein microarrays proposed above as a surrogate to the bone marrow
and tumor analysis. Approximately 10 ml of blood will be drawn using a CPT collection tube
(Becton Dickinson). The blood will be centrifuged and the buffy coat layer of white blood cells will
be removed, washed in cold PBS and pelleted by centrifugation. The DNA will be processed
using a column purification technique (Qiagen), or the buffy coat pellet will be frozen for future
DNA extraction.
7.1.3
Archival tissue
Archival tissue blocks will be collected for genomic DNA extraction for B-Raf mutational analysis
in the laboratory of Dr. Paul Meltzer. This process will be streamlined using screening methods
described in section 7.6.
21
7.2
Pharmacoproteomic analysis
7.2.1
The primary targets of pharmacoproteomic modulation to be measured were defined
based upon the preclinical signaling data. They are listed below
Survival/Proliferation
Angiogenesis
Apoptosis
Other
AKT
p-AKT
eNOS
p-eNOS
PARP
Cleaved-PARP
PSA
ERK 1 / 2
p-ERK 1 / 2
PDGFRE
p-PDGFRE
Caspase 9
Cleaved
Caspase-9
Cyclin D1
CD31
Caspase 3
Cleaved
Caspase-3
7.2.2
Should additional tissue or TLA arrays be available, the following targets will be
characterized. These will include but are not limited to the following:
Survival/Proliferation
Angiogenesis
Apoptosis
Other
mTOR
p-mTOR
D-smooth muscle actin
p53
PSMA
EGFR
p-EGFR
Pyk2
p-Pyk2
GSK3ß
p-GSK3ß
Cytokeratin-1
Src
p-Src
VEGFR-2
p-bad
NFkB
p-NFkB
p-Bcl-2
STAT1
p-STAT1
TGFa
p38
Phospho-p38
Jak1
pJak1
IkB
p-IkB
IGFR
7.2.3.
Provided that the following antibodies be validated for usage and adequate tissue or TLA
arrays be available, the following additional targets will be characterized:
Survival/Proliferation
Angiogenesis
Apoptosis
PCNA
DvE3 complex
Bad
Fos
CD34
Annexin V
Raf
VEGFR-1
Bcl-2
Ras
bFGF
CREB
vWF
Rho
Factor VIII
Jun
pJun
pIkB
Any unused tissue collected during the study will be saved for future studies, including
assessment of the differences in gene expression/protein profiles in pre- and post-treatment using
cDNA and protein microarray analyses in addition to other genomic and proteomic technologies.
Consent for such procedures will be procured at the time of study enrollment.
22
7.4 Imaging studies
Non-invasive imaging has become a standard tool in the clinic to monitor primary and metastatic solid
tumors. CT scan and bone scan will be performed on all patients at study entry and after every 2 cycles to
assess clinical response to BAY 43-9006.
7.5 Assessment of the pharmacokinetic parameters of BAY 43-9006
Blood samples will be obtained serially from prior to ingestion until 24 hours post-dose at the following
time points: immediately pre-dose, and at 0.25, 0.50, 1, 2, 4, 6, 8, 12, and 24 hours after ingestion, and
then at each clinic visit. In the event that inpatient admission is not possible, PKs may be done on an
outpatient basis. When outpatient PKs are being collected an hour 12 PK will not be required. The Clinical
Pharmacology Research Core of Dr. William D. Figg will coordinate rapid acquisition and evaluation of
patient samples. The pharmacokinetic characteristics of BAY 43-9006 in patients with AIPC will be
evaluated using the WinNonlin software (Pharsight, Mountain View, CA). The maximum concentration,
time to maximum concentration, the area under the curve extrapolated to infinity, and the apparent
terminal half-life will be calculated. Pharmacodynamic study will address any correlation in BAY 43-9006
concentration with disease response and/or toxicities.
7.6
B-Raf mutation analysis
It has recently been found that B-Raf is commonly mutated in human tumors. To determine if BAY 43-
9006 preferentially inhibits tumors with mutant B-Raf, mutational analysis of B-Raf using the following
paradigm:
Initial screening for B-Raf mutation will be executed by protein lysate array analysis. The most frequently
observed mutation in B-Raf is the V599E [31] amino acid substitution. Dr. Meltzer’s group has developed
a monoclonal antibody specific to this mutation (unpublished data). Lysate arrays will be optimized with
this monoclonal antibody and then will be used to assess expression of this BRAF mutation. . Detection of
this protein product will prompt allele specific PCR analysis of this region of the tumor genome using a
recut from the tumor biopsies obtained for the protocol. No germline analysis will be done. Additionally,
once a cohort of responders has been identified, genomic DNA will be extracted from tissue blocks for
allele specific PCR in the other commonly mutated region, T1769A.
7.7
Labeling, Storage, and Tracking
x All labels used must be freezer-proof.
x Barcode labels will be used in this study. A sample of the barcode will
be provided to the processing laboratory by Dr. Figg’s laboratory
before use because some DNA processing laboratories have
encountered scanning incompatibility due to inclusion of hidden digits
in barcode labels.
x Label each collection tube with the following information:
- unique sample I.D.
- study I.D. (NCI protocol number, etc.)
x All data associated with samples is entered into the Clinical
Pharmacology Program’s “Patient Sample Database Management
System” (PSDMS) - Labrador. This is a secure program that can only
be accessed by authorized users in Dr. Figg’s lab. PSDMS creates a
unique barcode ID for every sample and sample box which cannot be
traced back to patients without PSDMS access
23
x The data recorded for each sample includes the patient ID, name, trial
name/protocol number, time drawn, cycle time point, dose, material
type, as well as box and freezer location. There are patient
demographics that can be obtained to correlate with the samples
through the PSDMS system. For each sample, there are associated
processing notes (i.e., delay in sample processing, storage conditions
on the ward, etc.). Bar-coded samples are stored in bar-coded boxes in
a locked freezer at either -20 or -85qC according to stability
requirements. These freezers are located onsite in Dr. Figg’s lab and
offsite at NCI Frederick Central Repository Services (Fisher
Bioservices) in Frederick, MD. Samples will be stored until requested
by the researcher assigned to the protocol (however, those requests
must come from a member of Dr. Figg’s laboratory with PSDMS
access/clearance). All requests are monitored and tracked in the
PSDMS system. All researchers are required to sign a form stating that
the samples are only to be used for research purposes associated with
this trial (as per the IRB approved protocol – that protocol is stored in
the PSDMS system) and that any unused samples must be returned to
Dr. Figg’s laboratory.
x After collection, blood samples must be refrigerated (+ 4°C) or frozen
(see chart below) at the site of collection and transported to the central
reference laboratory or designated DNA processing laboratory as soon
as possible.
Option
Storage
Temperatur
e at
Treatment
Site
Maximum
Duration of
Storage at
Treatment
Site
Transport
Temperature
Delivery
Time
1
+ 4°C
(fridge)
24 hours
0 - 4°C (ice
blocks)
24 hours
2
+ 4°C
(fridge)
24 hours
Less than -20°C
(dry ice)
24-72
hours
x Samples must not be thawed and then re-frozen at any point.
Protocol Completion/Sample Destruction
x Once primary research objectives for the protocol are achieved,
intramural researchers can request access to remaining samples
providing they have an IRB approved protocol and patient consent.
24
x Samples, and associated data, will be stored permanently unless the
patient withdraws consent. If researchers have samples remaining once
they have completed all studies associated with the protocol, they must
be returned to Dr. Figg’s laboratory.
The PI will report destroyed samples to the IRB if samples become unsalvageable
because of environmental factors (ex. broken freezer or lack of dry ice in a shipping
container) or if a patient withdraws consent. Samples will also be reported as lost if they
are lost in transit between facilities or misplaced by a researcher. Dr. Figg’s laboratory
will report any freezer problems, lost samples or other problems associated with samples
to the IRB, the NCI Clinical Director, and the office of the CCR, NCI.
25
8.
STUDY CALENDAR
Schedules shown in the Study Calendar below are provided as an example and should be modified
as appropriate (+/- 1-2 days to allow for clinic variations around federal holidays).
Baseline evaluations are to be conducted within 1 week prior to administration of protocol therapy. Scans
and x-rays must be done 4 weeks prior to the start of therapy. In the event that the patient’s condition is
deteriorating, laboratory evaluations should be repeated within 48 hours prior to initiation of the next cycle
of therapy.
Pre-
Study
C1D1
C1D2-
28
C2D1
C3D1
C4D1
C5D1
C6D1
C7D1
Q4
weeks
Q12
weeks
Off
Study
c
BAY 43-9006
X
X
X
X
X
X
X
X
X
X
Informed consent
X
Demographics
X
Medical history
X
X
X
X
X
X
X
X
X
X
X
Concurrent Meds
X
X
X
X
X
X
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
Performance status
X
X
X
X
X
X
X
X
X
X
X
CBC w/diff, plts, PT, PTT
X
X
X
X
X
X
X
X
X
X
X
Serum chemistry
b
X
X
X
X
X
X
X
X
X
X
X
PSA
X
X
X
X
X
X
X
X
X
X
X
EKG (as indicated)
X
Adverse event evaluation
X
X
X
X
X
X
X
X
X
X
Tumor measurements
X
X
X
X
X
Radiological Evaluation
X
X
X
X
X
X
Tumor Biopsy OR Bone
Marrow Biopsy and Aspirate
X
X
Other correlative studies
X
X
a: BAY 43-9006: Dose as assigned; route/schedule.
b: Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, LDH, phosphorus, potassium,
total protein, SGOT(AST), SGPT(ALT), sodium, amylase, lipase
c: Off-study evaluation. Two consecutive measurements taken 4 weeks apart must be used to document progressive disease if the patient
is removed from study for this reason.
26
9.
MEASUREMENT OF EFFECT
For the purposes of this study, patients should be reevaluated for response every 8 weeks for the first 6
months of the study. After 6 months, CT and bone scans should be obtained at least every 3 months to
monitor disease status while on BAY 43-9006. In addition to a baseline scan, confirmatory scans should
also be 4 weeks following initial documentation of objective response.
9.1
Definitions
Response and progression will be evaluated in this study using the new international criteria proposed by
the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000].
Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the
RECIST criteria. Note: Lesions are either measurable or non-measurable using the criteria provided
below. The term “evaluable” in reference to measurability will not be used because it does not provide
additional meaning or accuracy.
9.1.1
Measurable disease
Measurable lesions are defined as those that can be accurately measured in at least
one dimension (longest diameter to be recorded) as >20 mm with conventional
techniques (CT, MRI, x-ray) or as >10 mm with spiral CT scan. All tumor
measurements must be recorded in millimeters (or decimal fractions of centimeters).
9.1.2
Non-measurable disease
All other lesions (or sites of disease), including small lesions (longest diameter <20
mm with conventional techniques or <10 mm using spiral CT scan), are considered
non-measurable disease. Bone lesions, leptomeningeal disease, ascites,
pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast
disease, abdominal masses (not followed by CT or MRI), and cystic lesions are all
non-measurable.
9.1.3
Target lesions
All measurable lesions up to a maximum of five lesions per organ and 10 lesions in
total, representative of all involved organs, should be identified as target lesions and
recorded and measured at baseline. Target lesions should be selected on the basis
of their size (lesions with the longest diameter) and their suitability for accurate
repeated measurements (either by imaging techniques or clinically). A sum of the
longest diameter (LD) for all target lesions will be calculated and reported as the
baseline sum LD. The baseline sum LD will be used as reference by which to
characterize the objective tumor response.
9.1.4
Non-target lesions
All other lesions (or sites of disease) should be identified as non-target lesions and
should also be recorded at baseline. Non-target lesions include measurable lesions
that exceed the maximum numbers per organ or total of all involved organs as well as
non-measurable lesions. Measurements of these lesions are not required, but the
presence or absence of each should be noted throughout follow-up.
9.2
Guidelines for Evaluation of Measurable Disease
All measurements should be taken and recorded in metric notation using a ruler or calipers. All baseline
evaluations should be performed as closely as possible to the beginning of treatment and never more than
4 weeks before the beginning of the treatment.
Note: Tumor lesions that are situated in a previously irradiated area might or might not be considered
measurable.
The same method of assessment and the same technique should be used to characterize each identified
and reported lesion at baseline and during follow-up. Imaging-based evaluation is preferred to evaluation
27
by clinical examination when both methods have been used to assess the antitumor effect of a treatment.
Clinical lesions. Clinical lesions will only be considered measurable when they are superficial (e.g., skin
nodules and palpable lymph nodes). In the case of skin lesions, documentation by color photography,
including a ruler to estimate the size of the lesion, is recommended.
Chest x-ray. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined
and surrounded by aerated lung. However, CT is preferable.
Conventional CT and MRI. These techniques should be performed with cuts of 10 mm or less in slice
thickness contiguously. Spiral CT should be performed using a 5 mm contiguous reconstruction algorithm.
This applies to tumors of the chest, abdomen, and pelvis. Head and neck tumors and those of extremities
usually require specific protocols.
Ultrasound (US). When the primary endpoint of the study is objective response evaluation, US should
not be used to measure tumor lesions. It is, however, a possible alternative to clinical measurements of
superficial palpable lymph nodes, subcutaneous lesions, and thyroid nodules. US might also be useful to
confirm the complete disappearance of superficial lesions usually assessed by clinical examination.
Endoscopy, Laparoscopy. The utilization of these techniques for objective tumor evaluation has not yet
been fully and widely validated. Their uses in this specific context require sophisticated equipment and a
high level of expertise that may only be available in some centers. Therefore, the utilization of such
techniques for objective tumor response should be restricted to validation purposes in reference centers.
However, such techniques may be useful to confirm complete pathological response when biopsies are
obtained.
Cytology, Histology. These techniques can be used to differentiate between partial responses (PR) and
complete responses (CR) in rare cases (e.g., residual lesions in tumor types, such as germ cell tumors,
where known residual benign tumors can remain).
The cytological confirmation of the neoplastic origin of any effusion that appears or worsens during
treatment when the measurable tumor has met criteria for response or stable disease is mandatory to
differentiate between response or stable disease (an effusion may be a side effect of the treatment) and
progressive disease.
9.3
Response Criteria
9.3.1
Evaluation of target lesions
Complete Response (CR): Disappearance of all target lesions
Partial Response (PR):
At least a 30% decrease in the sum of the longest
diameter (LD) of target lesions, taking as reference
the baseline sum LD
Progressive Disease (PD):
At least a 20% increase in the sum of the LD of
target lesions, taking as reference the smallest sum
LD recorded since the treatment started or the
appearance of one or more new lesions
Stable Disease (SD):
Neither sufficient shrinkage to qualify for PR nor
sufficient increase to qualify for PD, taking as
reference the smallest sum LD since the treatment
started
9.3.2
Evaluation of non-target lesions
28
Complete Response (CR):
Disappearance of all non-target lesions and
normalization of tumor marker level
Incomplete Response/
Stable Disease (SD):
Persistence of one or more non-target lesion(s)
and/or maintenance of tumor marker level above the
normal limits
Progressive Disease (PD):
Appearance of one or more new lesions and/or
unequivocal progression of existing non-target
lesions
Although a clear progression of “non-target” lesions only is exceptional, in such
circumstances the opinion of the treating physician should prevail, and the
progression status should be confirmed at a later time by the review panel (or study
chair).
Note: If tumor markers are initially above the upper normal limit, they must normalize
for a patient to be considered in complete clinical response.
9.3.3
Evaluation of best overall response
The best overall response is the best response recorded from the start of the
treatment until disease progression/recurrence (taking as reference for progressive
disease the smallest measurements recorded since the treatment started). The
patient's best response assignment will depend on the achievement of both
measurement and confirmation criteria (see section 9.3.1).
29
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Incomplete
response/SD
No
PR
PR
Non-PD
No
PR
SD
Non-PD
No
SD
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
Note:
&
Patients with a global deterioration of health status requiring discontinuation of
treatment without objective evidence of disease progression at that time should be
classified as having “symptomatic deterioration.” Every effort should be made to
document the objective progression, even after discontinuation of treatment.
&
In some circumstances, it may be difficult to distinguish residual disease from normal
tissue. When the evaluation of complete response depends on this determination, it
is recommended that the residual lesion be investigated (fine needle aspirate/biopsy)
before confirming the complete response status.
9.4
Confirmatory Measurement/Duration of Response
9.4.1
Confirmation
To be assigned a status of PR or CR, changes in tumor measurements must be
confirmed by repeat assessments that should be 4 weeks after the criteria for
response are first met. In the case of SD, follow-up measurements must have met
the SD criteria at least once after study entry at a minimum interval 8 weeks (see
section 9.3.3).
9.4.2
Duration of overall response
The duration of overall response is measured from the time measurement criteria are
met for CR or PR (whichever is first recorded) until the first date that recurrent or
progressive disease is objectively documented (taking as reference for progressive
disease the smallest measurements recorded since the treatment started).
The duration of overall CR is measured from the time measurement criteria are first
met for CR until the first date that recurrent disease is objectively documented.
30
9.4.3
Duration of Stable Disease
Stable disease is measured from the start of the treatment until the criteria for
progression are met, taking as reference the smallest measurements recorded since
the treatment started.
9.5
Biochemical Response Criteria –PSA measurements (PSA Consensus Criteria) (Bubley et al.
1999)
9.5.1
PSA Decline of 50%
A decline of PSA of at least 50% (confirmed by a second value at least 4 weeks after the first)
with no other evidence of disease progression.
9.5.2. PSA Progression (all progression dates require to be confirmed by a second value after
the first no sooner than 4 weeks after the initial measurement)
A 50% increase in PSA over nadir (confirmed by a second reading four weeks later) in patients
whose PSA has fallen by at least 50%. PSA increase must be at least 5ng/ml.
9.5.2.1 A 25% increase in PSA over nadir (confirmed by a second reading) in patients
whose PSA has not fallen by at least 50%. PSA increase must be at least 5ng/ml.
9.5.2.2 A 25% increase in PSA over baseline in patients whose PSA has not decreased.
PSA increase must be at least 5ng/ml.
9.5.3
Time to PSA Progression
The time between the first day of treatment to the day of PSA progression as described in 9.5.2.
the day of progression is defined as the first study day when the PSA level meets progression
criteria (not the day of verification).
9.5.4 Per amendment D, Biochemical Response Criteria will continue to be measured as a
primary endpoint, however patients may continue to receive BAY 43-9006 as long as they do not
have clear evidence of radiographic or clinical progression.
9.6
Progression-Free Survival
The primary objective of this study is to determine whether BAY 43-9006, when used to treat metastatic
androgen independent prostate cancer (AIPC), is associated with 50% of patients progression free at 4
months by PSA and clinical criteria. Patient monitoring studies and definitions of response are defined
above. Please refer to the statistics section for further details.
Per Amendment D, a secondary objective of this study is to determine whether BAY 43-9006, when used
to treat metastatic AIPC, is associated with 50% of patients progression free at 4 months by clinical and
radiographic criteria. The 22 patients treated on the first stage of this protocol will be retrospectively
evaluated with respect to this secondary endpoint. Please refer to the statistics section for further details.
9.7
Response Review- N/A
10.
REGULATORY AND REPORTING REQUIREMENTS
Expedited adverse event (AE) reporting for this study is via AdEERS (Adverse Event Expedited Reporting
System), accessed via the secure CTEP web site
https://webapps.ctep.nci.nih.gov/openapps/plsql/gadeers_main$.startup). The reporting procedures to be
followed are presented in the “NCI Guidelines: Expedited Adverse Event Reporting Requirements for NCI
Investigational Agents” which can be downloaded from the CTEP web site
(http://ctep.cancer.gov/reporting/adeers.html).
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse
31
Events (CTCAE) version 3.0 will be utilized for adverse event reporting. All appropriate treatment areas
should have access to a copy of the CTCAE version 3.0. A list of adverse events that have occurred or
might occur (Reported Adverse Events and Potential Risks) can be found in Section 6 (Pharmaceutical
Information). A copy of the CTCAE version 3.0 can be downloaded from the CTEP web site
(http://ctep.cancer.gov/reporting/ctc.html).
10.1
Expedited Adverse Event Reporting
(AE; formerly known as Adverse Drug Reaction)
Expedited reports are submitted to CTEP via the secure AdEERS application accessed via the CTEP web
site (https://webapps.ctep.nci.nih.gov/openapps/plsql/gadeers_main$.startup) and to the NCI IRB. Those
AEs that do not require expedited reporting must be reported in routine (CDUS) study data submissions.
AEs reported through AdEERS must also be reported in routine study data submissions.
10.1.1 Expedited Reporting Guidelines
Phase 2 and 3 Trials Utilizing an Agent under a CTEP IND: AdEERS Reporting Requirements for
Adverse Events That Occur Within 30 Days1 of the Last Dose of the Investigational Agent
Grade 1
Grade 2
Grade 2
Grade 3
Grade 3
Grades
4 & 5
2
Grades
4 & 5
2
Unexpected
Expected
Unexpected
and
Expected
Unex-
pected
Expected
with
Hospitali-
zation
without
Hospitali-
zation
with
Hospitali-
zation
without
Hospitali-
zation
Unex-
pected
Expected
Unrelated
Unlikely
Not
Required
Not
Required
Not
Required
10
Calendar
Days
Not
Required
10
Calendar
Days
Not
Required
10
Calendar
Days
10
Calendar
Days
Possible
Probable
Definite
Not
Required
10
Calendar
Days
Not
Required
10
Calendar
Days
10
Calendar
Days
10
Calendar
Days
Not
Required
24-Hour;
5 Calendar
Days
10
Calendar
Days
1 Adverse events with attribution of possible, probable, or definite that occur greater than 30 days after the last
dose of treatment with an agent under a CTEP IND require reporting as follows:
AdEERS 24-hour notification followed by complete report within 5 calendar days for:
x
Grade 4 and Grade 5 unexpected events
AdEERS 10 calendar day report:
x
Grade 3 unexpected events with hospitalization or prolongation of hospitalization
x
Grade 5 expected events
2 Although an AdEERS 24-hour notification is not required for death clearly related to progressive disease, a full report is
required as outlined in the table.
December 15, 2004
Note: All deaths on study must be reported using expedited reporting regardless of causality.
Attribution to treatment or other cause should be provided.
x
Expedited AE reporting timelines defined:
¾ “24 hours; 5 calendar days” – The investigator must initially report the AE via AdEERS within
24 hours of learning of the event followed by a complete AdEERS report within 5 calendar
days of the initial 24-hour report.
¾ “10 calendar days” - A complete AdEERS report on the AE must be submitted within 10
calendar days of the investigator learning of the event.
x
Any medical event equivalent to CTCAE grade 3, 4, or 5 that precipitates hospitalization (or
prolongation of existing hospitalization) must be reported regardless of attribution and designation
as expected or unexpected with the exception of any events identified as protocol-specific
32
expedited adverse event reporting exclusions.
x
Any event that results in persistent or significant disabilities/incapacities, congenital anomalies, or
birth defects must be reported via AdEERS if the event occurs following treatment with an agent
under a CTEP IND.
x
Use the NCI protocol number and the protocol-specific patient ID provided during trial registration
on all reports.
10.1.2 Expedited Adverse Event Reporting Exclusions- N/A
10.1.3 Secondary AML/MDS
Investigators are required to report cases of secondary AML/MDS occurring on or following treatment on
NCI-sponsored chemotherapy protocols using the NCI/CTEP Secondary AML/MDS Report Form. This
form can be downloaded from the CTEP web site (http://ctep.cancer.gov/reporting/index.html). Second
malignancies and non-AML/MDS secondary malignancies (e.g., endometrial cancer in a breast cancer
patient receiving tamoxifen) should NOT be reported via AdEERS but should be submitted as part of the
study results via routine CDUS reporting.
10.2
Data Reporting
This study will be monitored by the Clinical Data Update System (CDUS) version 3.0. Cumulative CDUS
data will be submitted quarterly to CTEP by electronic means. Reports are due January 31, April 30, July
31, and October 31. Instructions for submitting data using the CDUS can be found on the CTEP web site
(http://ctep.cancer.gov/reporting/cdus.html).
10.3
CTEP Multicenter Guidelines- N/A
10.4
Cooperative Research and Development Agreement (CRADA)/Clinical Trials Agreement
(CTA)
The agent(s) supplied by CTEP, DCTD, NCI used in this protocol is/are provided to the NCI under a
Collaborative Agreement (CRADA, CTA) between the Pharmaceutical Company(ies) (hereinafter referred
to as ACollaborator(s)@) and the NCI Division of Cancer Treatment and Diagnosis. Therefore, the
following obligations/guidelines, in addition to the provisions in the AIntellectual Property Option to
Collaborator@ contained within the terms of award, apply to the use of the Agent(s) in this study:
1. Agent(s) may not be used for any purpose outside the scope of this protocol, nor can
Agent(s) be transferred or licensed to any party not participating in the clinical study.
Collaborator(s) data for Agent(s) are confidential and proprietary to Collaborator(s) and
shall be maintained as such by the investigators. The protocol documents for studies
utilizing investigational Agents contain confidential information and should not be shared
or distributed without the permission of the NCI. If a copy of this protocol is requested by
a patient or patient’s family member participating on the study, the individual should sign a
confidentiality agreement. A suitable model agreement can be downloaded from:
http://ctep.cancer.gov
2. For a clinical protocol where there is an investigational Agent used in combination with
(an)other investigational Agent(s), each the subject of different collaborative agreements ,
the access to and use of data by each Collaborator shall be as follows (data pertaining to
such combination use shall hereinafter be referred to as "Multi-Party Data.@):
a.
NCI must provide all Collaborators with prior written notice regarding the
existence and nature of any agreements governing their collaboration with NIH,
the design of the proposed combination protocol, and the existence of any
obligations that would tend to restrict NCI's participation in the proposed
combination protocol.
33
b.
Each Collaborator shall agree to permit use of the Multi-Party Data from the
clinical trial by any other Collaborator solely to the extent necessary to allow said
other Collaborator to develop, obtain regulatory approval or commercialize its own
investigational Agent.
c.
Any Collaborator having the right to use the Multi-Party Data from these trials
must agree in writing prior to the commencement of the trials that it will use the
Multi-Party Data solely for development, regulatory approval, and
commercialization of its own investigational Agent.
3.
Clinical Trial Data and Results and Raw Data developed under a collaborative agreement will be
made available exclusively to Collaborator(s), the NCI, and the FDA, as appropriate. All data
made available will comply with HIPAA regulations
4.
When a Collaborator wishes to initiate a data request, the request should first be sent to the NCI,
who will then notify the appropriate investigators (Group Chair for Cooperative Group studies, or
PI for other studies) of Collaborator's wish to contact them.
5.
Any data provided to Collaborator(s) for Phase 3 studies must be in accordance with the
guidelines and policies of the responsible Data Monitoring Committee (DMC), if there is a DMC for
this clinical trial.
6.
Any manuscripts reporting the results of this clinical trial must be provided to CTEP for immediate
delivery to Collaborator(s) for advisory review and comment prior to submission for publication.
Collaborator(s) will have 30 days from the date of receipt for review. Collaborator shall have the
right to request that publication be delayed for up to an additional 30 days in order to ensure that
Collaborator’s confidential and proprietary data, in addition to Collaborator(s)’s intellectual
property rights, are protected. Copies of abstracts must be provided to CTEP for forwarding to
Collaborator(s) for courtesy review as soon as possible and preferably at least three (3) days prior
to submission, but in any case, prior to presentation at the meeting or publication in the
proceedings. Press releases and other media presentations must also be forwarded to CTEP prior
to release. Copies of any manuscript, abstract and/or press release/ media presentation should be
sent to:
Regulatory Affairs Branch, CTEP, DCTD, NCI
Executive Plaza North, Suite 7111
Bethesda, Maryland 20892
FAX 301-402-1584
Email: anshers@ctep.nci.nih.gov
The Regulatory Affairs Branch will then distribute them to Collaborator(s). No publication,
manuscript or other form of public disclosure shall contain any of Collaborators
confidential/ proprietary information.
11.
STATISTICAL CONSIDERATIONS
11.1
Study Design/Endpoints
The study was originally designed to have a two-stage design with 22 and then up to a total of 46 patients
evaluating progression using PSA criteria. The results from the first stage were inadequate to justify
accrual to the second stage. However, per amendment D, waiver of the stopping rule is requested to allow
for accrual to the second stage.
The primary objective of this study is to determine whether BAY 43-9006, when used to treat metastatic
AIPC, is associated with having 50% of patients progression free at 4 months by clinical, radiographic and
PSA criteria. The secondary objective of this study is to determine the time to progression measured by
34
clinical and radiographic criteria. If this is found to be the case, then this agent will be considered
potentially useful when combined with other anticancer agents to be tested in later trials. Data from
previous trials of NCI patients with similar eligibility requirements demonstrated a 2.1 month median
progression free survival when using thalidomide (n=63) [32]. Median progression free survival on
ketoconazole alone is expected to be 4 months based on previous trials[33]. Ketoconazole is recognized
as a standard therapy alterative to cytotoxic chemotherapy in the setting of failure of primary hormonal
therapy with GnRH agonists and anti-androgen therapy. The Eastern Cooperative Oncology Group is
currently sponsoring a phase III clinical trial comparing ketoconazole to the combination of estramustine
and docetaxel. Median progression free survival on ketoconazole alone is expected to be 4 months based
on previous trials [34, 35]. Based on these results, it would be useful to demonstrate whether BAY 43-
9006 is able to induce progression free survival in 50% of patients at the 4 month (approximately day 113
evaluation) time point.
The study will be conducted as a two-stage optimal design (Simon 1989)[29]. Using alpha=0.10 and
beta=0.10 as acceptable error probabilities, the trial will target 50% as the desirable proportion of patients
who are still without progression by clinical, radiographic and PSA criteria at the 4th monthly evaluation
(p1=0.50; see section 9.5.1 for details), and will be considered inadequate if only a fraction consistent with
30% are without progression by the same evaluation time (p0=0.30).
Initially, 22 patients will be enrolled and evaluated for progression. The enrollment will be
temporarily halted after the 22nd patient unless we know that 8 patients have passed the 4 month
point without progression. If 8 or more of the first 22 patients enrolled on the trial have not
progressed as defined in Section 9.3 and 9.4 at the 4th evaluation (day 113, approximately), then
enrollment will continue until 46 patients have been enrolled. If, among the first 22 patients
enrolled, 7 or fewer are able to be progression free at the 4 month evaluation, then the original
design specified that no further patients will be enrolled once such a determination has been
made. If 18 or more of the total cohort of 46 patients have been found to be progression free at 4
months, then this will indicate an adequate progression free probability to be worthy of further
consideration in future trials. On the other hand, if 8-17 of 46 are progression free at 4 months,
this will be considered insufficient. Under the null hypothesis (30% progression free at 4 months),
the probability of being able to stop accrual after 22 patients have been evaluated at 4 months is
67%. However, under amendment D, the stopping rule will be waived due to potential benefit
identified in patients during the first stage, despite failure to meet criteria established for continuing
accrual. The total set of 46 patients will be evaluated with respect to progression free survival,
using clinical, radiographic and PSA criteria to primarily focus on 4 month progression free
survival. In addition, progression free survival evaluated by clinical and radiographic measures
only will be determined on all evaluable patients from whom this may be determined.
Given the difficulties in interpreting progression free rates in our patients compared to historical data, the
response rate will be included as a secondary clinical endpoint.
In addition to evaluation of the proportion progression free at 4 months, the progression free
survival will also be analyzed via a Kaplan-Meier curve. This will be done for both progression
free survival evaluated by clinical, radiographic and PSA criteria, as well as secondarily based
only on clinical and radiographic criteria. This latter, secondary, evaluation will be based on all
patients who are able to be assessed by these criteria in either the first (retrospectively) or second
stage of accrual.
11.2
Sample Size/Accrual Rate
Based on previous efforts in recruiting patients with this disease onto trials at the NCI, it is anticipated that
30 patients per year may be able to enroll onto this protocol. Thus, it is expected that accrual to this trial
can be completed in approximately 1.5 years if all 46 patients are to be enrolled
11.3
Stratification Factors
35
There are no stratification factors
11.4
Analysis of Secondary Endpoints
Proteomic, PSA, pharmacokinetic, and molecular endpoints will be evaluated on the protocol in all
available enrolled patients. These will all be considered exploratory analyses, and will not have their
statistical results adjusted for multiple comparisons. However, all interesting findings will be carefully
interpreted as hypothesis generating.
11.5 Reporting and Exclusions
11.5.1 Evaluation of toxicity. All patients will be evaluable for toxicity from the time of their first
treatment with BAY 43-9006
11.5.2 Evaluation of response. All patients included in the study must be assessed for response to
treatment, even if there are major protocol treatment deviations or if they are ineligible. Each patient will
be assigned one of the following categories: 1) complete response, 2) partial response, 3) stable disease,
4) progressive disease, 5) early death from malignant disease, 6) early death from toxicity, 7) early death
because of other cause, or 9) unknown (not assessable, insufficient data). [Note: By arbitrary convention,
category 9 usually designates the “unknown” status of any type of data in a clinical database.]
All of the patients who met the eligibility criteria (with the possible exception of those who received no
study medication) should be included in the main analysis of the response rate. Patients in response
categories 4-9 should be considered as failing to respond to treatment (disease progression). Thus, an
incorrect treatment schedule or drug administration does not result in exclusion from the analysis of the
response rate. Precise definitions for categories 4-9 will be protocol specific.
12.
HUMAN SUBJECTS PROTECTIONS
12.1
Rationale for subject selection
Subjects treated on this study, will be individuals with metastatic prostate cancer, which has recurred (or
persisted) after appropriate standard treatment. Individuals of any race or ethnic group will be eligible for
this study. Eligibility assessment will be based solely on the patient’s medical status. Recruitment of
patients onto this study, will be through standard CCR mechanisms. No special recruitment efforts will be
conducted.
12.2
Evaluation of benefits and risks/discomforts
The potential benefit to a patient that goes onto study, is a reduction in the bulk of their tumor and
improvement in their bony lesions, which may or may not have favorable impact on symptoms and/or
survival. Potential risks include the possible occurrence of any of a range of side effects, that are listed in
the Consent Document (Please refer to http://ctep.cancer.gov/reporting/adeers.html to review the up-to-
date expected adverse event list for BAY 43-9006). The procedure for protecting against or minimizing
risks, will be to medically evaluate patients on a regular basis as described in Section 9.
12.3
Risks to patients in relation to anticipated benefits
12.3.1 For patients with androgen-independent prostate cancer, median survival is in the range
of 12-18 months. Potential risks include the possible occurrence of any of a range of side effects
listed in section 6. Please refer to http://ctep.cancer.gov/reporting/adeers.html to review the up-to-
date expected adverse event list for BAY 43-9006.
12.3.2 Risk of serial biopsies: All care will be taken to minimize risks that may be incurred by
tumor sampling. However, there are procedure-related risks (such as bleeding, infection and
visceral injury) that will be explained fully during informed consent. If patients suffer any physical
injury as a result of the biopsies, immediate medical treatment is available at the NIH’s Clinical
Center in Bethesda, Maryland. Although no compensation is available, any injury will be fully
36
evaluated and treated in keeping with the benefits or care to which patients are entitled under
applicable regulations.
12.4
Consent process
Patients will meet with an associate or principal investigator on the trial in the Prostate Cancer Clinic,
during the initial evaluation for this study. During that meeting, the investigator will inform patients of the
purpose, alternatives, treatment plan, research objectives and follow-up of this trial. The investigator will
then provide a copy of the IRB-approved informed consent document that is included in this protocol. The
patient will be allowed to take as much time as he wishes, in deciding whether or not he wishes to
participate. If a prolonged period of time expires during the decision making process (several weeks, as
an example), it may be necessary to reassess the patient for protocol eligibility. A copy of the signed
informed consent will be placed in the patient's medical record and the original held in the Protocol Office.
12.5
All patients must have a signed informed consent form and an on-study (confirmation of eligibility)
form filled out and signed by a participating investigator before entering on the study.
12.6
Patient Records and Quality Assurance
Quality assurance complete records must be maintained on each patient treated on the protocol. These
records should include primary documentation (e.g.: laboratory report slips, X-ray reports, scan reports,
pathology reports, physicians notes, etc.) which confirm that:
12.6.1 The patient met all eligibility criteria
12.6.2 Signed informed consent was obtained prior to treatment
12.6.3 Treatment was given according to protocol (dated notes about doses given,
complications, and clinical outcomes).
12.6.4 Toxicity was assessed according to protocol (laboratory report slips, etc.)
12.6.5 Response was assessed according to protocol (X-ray, scan, lab reports, date noted on
clinical assessment, as appropriate).
12.6.6 Drug Accountability
The unused BAY 43-9006 (partial bottles, empty bottles, and full bottles) will be returned for drug
accountability at each clinic visit. An oral study agent case report form will be used to document
drug accountability for each patient on this study. Unused agent, which is not returned to the
patient for the next dose cycle, will be disposed of according to the Procedure of Disposal of
Returned Oral agents.
12.6.7 Patients will use a diary to document daily drug intake and adverse events.
13.
Data and Safety Monitoring Plan
A complete CDUS report will be submitted to CTEP on a quarterly basis. Response data will be on a
quarterly basis as well. All adverse drug reactions will be reported to the NCI Institutional Review Board
(IRB) within 10 working days of the date of occurrence. Safety information from patients enrolled onto the
study will be gathered and reported. Any unusual toxicity will be explored for possible causative
mechanisms. The safety of the repetitive biopsy procedure will also be determined and reported.
13.1
Any unanticipated or unknown treatment- or drug-related toxicity(ies) and life-threatening and
lethal toxicity(ies) will be reported according to the DCT’s Guidelines for Reporting Adverse Drug
Reactions to the Investigational Drug Branch (301-230-2330; Fax 301-230-0159) within 24 hours, with a
copy sent to the NCI-IRB. All fatal events (NCI/CTEP grade V toxicity) will require a written report from the
37
Principal or Associate Investigator will follow within 10 working days. A written report, within 10 working
days, should be sent on CTEP ADR forms to:
Investigational Drug Branch
PO Box 30012
Bethesda, MD 20824
Clinical Associates and/or senior staff should notify the Principal Investigator at 301-435-8183 (Dr. Dahut),
Bldg.10, Rm 12N226 of the occurrence of such toxicity.
13.2
Adverse events listed in section 6 do not require ADEERS reporting except as otherwise
mandated by the guidelines (e.g., grade 3 with hospitalization, grade 4 or 5). The occurrence of any new
toxicity (not in the above list), regardless of grade, and all life threatening events (NCI/CTEP grade IV
toxicity) will be reported to the Drug Monitor, Investigational Drug Branch, CTEP, and the NCI IRB within
24 hours. An ADR form may be required. The Principal Investigator, Study Coordinator, or an Associate
Investigator will be responsible for completing the ADR form and for notifying the NCI’s Institutional
Review Board.
A summary of the ongoing study will be submitted to the NCI’s Institutional Review Board at 12 month
intervals and a final report will be sent within six months of study completion at the request of the
Institutional Review Board using the CTEP study summary form. The status reported will be submitted
and presented at upcoming NCI meetings as requested
38
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Goktas, S. and E.D. Crawford, Optimal hormonal therapy for advanced prostatic carcinoma.
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Beedassy, A. and G. Cardi, Chemotherapy in advanced prostate cancer. Semin Oncol, 1999.
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Pollock, P.M. and P.S. Meltzer, A genome-based strategy uncovers frequent BRAF mutations in
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Sawyers, C.L., Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid
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treatment of KIT-positive malignancies. J Clin Oncol, 2002. 20(6): p. 1692-703.
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Alavi, A., et al., Role of Raf in vascular protection from distinct apoptotic stimuli. Science, 2003.
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Bakin, R.E., et al., Constitutive activation of the Ras/mitogen-activated protein kinase signaling
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Bakin, R.E., et al., Attenuation of Ras signaling restores androgen sensitivity to hormone-
refractory C4-2 prostate cancer cells. Cancer Res, 2003. 63(8): p. 1975-80.
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Fu, Z., et al., Effects of raf kinase inhibitor protein expression on suppression of prostate cancer
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VEGF and its receptors. Anticancer Res, 2003. 23(5A): p. 3917-22.
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Wu, J., K. Haugk, and S.R. Plymate, Activation of pro-apoptotic p38-MAPK pathway in the
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Nicholson, B. and D. Theodorescu, Angiogenesis and prostate cancer tumor growth. J Cell
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Simon, R., Optimal two-stage designs for phase II clinical trials. Control Clin Trials, 1989. 10(1): p.
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Brown, R.S., et al., The comparative values of bone marrow aspirate and trephine for obtaining
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Pollock, P.M., et al., High frequency of BRAF mutations in nevi. Nat Genet, 2003. 33(1): p. 19-20.
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Figg, W.D., et al., A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients
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Figg, W.D., et al., A randomized, phase II trial of ketoconazole plus alendronate versus
ketoconazole alone in patients with androgen independent prostate cancer and bone metastases.
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Walczak, J.R. and M.A. Carducci, Phase 3 randomized trial evaluating second-line hormonal
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Small, E.J., et al., Ketoconazole retains activity in advanced prostate cancer patients with
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40
APPENDIX A
Performance Status Criteria
ECOG Performance Status Scale
Karnofsky Performance Scale
Grade
Descriptions
Percent
Description
100
Normal, no complaints, no evidence of
disease.
0
Normal activity. Fully active, able to
carry on all pre-disease performance
without restriction.
90
Able to carry on normal activity; minor
signs or symptoms of disease.
80
Normal activity with effort; some signs
or symptoms of disease.
1
Symptoms, but ambulatory.
Restricted in physically strenuous
activity, but ambulatory and able to
carry out work of a light or sedentary
nature (e.g., light housework, office
work).
70
Cares for self, unable to carry on normal
activity or to do active work.
60
Requires occasional assistance, but is
able to care for most of his/her needs.
2
In bed <50% of the time. Ambulatory
and capable of all self-care, but
unable to carry out any work activities.
Up and about more than 50% of
waking hours.
50
Requires considerable assistance and
frequent medical care.
40
Disabled, requires special care and
assistance.
3
In bed >50% of the time. Capable of
only limited self-care, confined to bed
or chair more than 50% of waking
hours.
30
Severely disabled, hospitalization
indicated. Death not imminent.
20
Very sick, hospitalization indicated.
Death not imminent.
4
100% bedridden. Completely
disabled. Cannot carry on any self-
care. Totally confined to bed or chair.
10
Moribund, fatal processes progressing
rapidly.
5
Dead.
0
Dead.
41
Appendix B: NCI/FDA Proteomics Program Standard Operating Procedure for Tissue Core
Collection- Needle Biopsy – Cryopreservation in OCT
Principle:
Core needle biopsies are used to sample tissue from a specific, defined location. These biopsies may
consist of normal, pre-malignant and malignant tissue due to the multi-level tissue sample that is obtained.
This type of sample is ideal for studying the micro-tumor environment.
Rapid freezing of the sample is required to prevent degradation of the proteins or RNA. Optimal Cutting
Temperature (OCT) compound is an alcohol polymer that is liquid at room temperature and a solid at –
20oC. This polymer is used to cryo-protect the tissue and provide a medium for cryo-sectioning.
Materials:
Cryomolds (Sakura Finetek Ca.t # 4728)
OCT (Sakura Finetek Cat. # 4583)
Dry ice
Ultra cold freezer (-700 to -800C)
Needle: 16 or 18 gauge
Permanent marker
Sterile forceps
Sterile Glass slides
Aluminum foil or 50ml Falcon tubes
Procedure:
1. Prepare all supplies prior to the biopsy procedure to avoid delay once the specimen has been
obtained.
2. Label the handle and the front surface of the cryomold with the sample or patient’s identifying
information.
3. Perform core needle biopsy.
4. Pick the core from the biopsy needle onto a sterile glass slide.
5. Fill cryomold about 1/3 full with OCT. Place the cryomold in dry ice to partially freeze the OCT.
The OCT should be jelly-like, not completely frozen.
6. Carefully lift the core biopsy by both ends with sterile forceps. Do not stretch the biopsy or it
will break.
7. Lay the biopsy as straight as possible in the OCT. Once the sample touches the OCT, you cannot
reposition it or the sample will break apart.
8. Quickly add OCT on top of the biopsy, completely covering the sample.
9. Ensure the sample is level and freeze immediately in dry ice.
10. Store wrapped in aluminum foil or in a 50ml Falcon tube at –70oC.
Note:
Do not lay the biopsy on frozen OCT and cover it with liquid OCT. The OCT will not fuse and will split into
two sections when cutting the frozen tissue sections.
42
Frozen Section Slides
1. Frozen sections for proteomic analysis should be cut at 5-8um on plain, uncoated glass
microscope slides.
2. The tissue section should be placed as close as possible to the center of the slide. Do not place
the frozen section at the end of the slide.
3. Two tissue sections from the same biopsy may be placed on the same glass slide if space
permits.
4. Do not allow the tissue section to air on the slide. Freeze immediately on dry ice or at –80oC.
Shipping Slides or Frozen Tissue
1. Ship slides/tissue in OCT on dry ice Monday through Thursday only.
2. Tissue should be embedded in OCT prior to shipment. Refer to procedure steps 5-10.
3. Seal slide box in a plastic bag with dessicant (such as Drierite crystals). Seal tissue in a 50ml
polypropylene Falcon tube, wrap in aluminum foil or place in a plastic bag.
4. Place dry ice on top of the plastic bag containing the slides/tissue.
5. Place any special instructions/inventory/shipping documents in the box.
6. Seal the box with tape.
7. Ship to:
Ginny Espina
National Cancer Institute
9000 Rockville Pike
Bldg 10 Room B1B53
Bethesda, MD 20892
301-435-7763
43
Appendix C: Cytochrome P450 3A4 Metabolized Drugs
Substrates
Acetaminophen
Dapsone
Levobupivicaine
Risperidone
Alfentanil
Dehydroepiandrostendione
Lidocaine
Ritonavir**
Alosetron
Delavirdine
Loratadine
Salmeterol
Alprazolam
Desmethyldiazepam
Losartan
Saquinavir
Amiodarone
Dexamethasone
Lovastatin
Sertindole
Amitriptyline (minor)
Dextromethorphan (minor)
Methadone
Sertraline
Amlodipine
Diazepam (minor)
Mibefradil
Sibutramine
Anastrozole
Digitoxin
Miconazole
Sildenafil citrate
Androsterone
Diltiazem
Midazolam
Simvastatin
Antipyrine
Disopyramide
Mifepristone
Sirolimus
Astemizole
Docetaxel
Mirtazapine
Sufentanil
Atorvastatin
Dofetilide (minor)
Montelukast
Tacrolimus
Benzphetamine
Dolasteron
Navelbine
Tamoxifen
Bepridil
Donepezil
Nefazodone
Temazepam
Bexarotene
Doxorubicin
Nelfinavir
Teniposide
Bromazepam
Doxycycline
Nevirapine
Terfenadine
Bromocriptine
Dronabinol
Nicardipine
Testosterone
Budesonide
Enalapril
Nifedipine
Tetrahydrocannabinol
Bupropion (weak)
Erythromycin
Niludipine
Theophylline
Buspirone
Estradiol
Nimodipine
Tiagabine
Busulfan
Ethenyl estradiol
Nisoldipine
Tolterodine
Caffeine
Ethosuximide
Nitrendipine
Toremifene
Cannabinoids
Etoposide
Omeprazole
(sulfonation)
Trazodone
Carbamazepine
Exemestane
Ondasetron
Tertinoin
Cerivastatin
Felodipine
Oral contraceptives
Triazolam
Cevimeline
Fentanyl
Orphenadrine
Troglitazone
Chlorpromazine
Fexofenadine
Paclitaxel
Troleandomycin
Cimetidine
Finasteride
Pantoprazole
Venlafaxine
Cisapride
Fluoxetine
Pimozide
Verapamil
Citalopram
Flutamide
Pioglitazone
Vinblastine
Clarithromycin
Glyburide
Pravastatin
Vincristine
Clindamycin
Granisetron
Prednisone
Warfarin
Clomipramine
Halofantrine
Progesterone
Yohimbine
Clonazepam
Hydrocortisone
Proguanil
Zaleplon (minor)
Clozapine
Hydroxyarginine
Propafenone
Zatoestron
Cocaine
Ifosfamide
Quercetin
Zileuton
Codeine
Imipramine
Quetiapine
Ziprasidone
Cortisol
Indinavir
Quinidine
Zolpidem
Cortisone
Isradipine
Quinine
Zonisamide
Cyclobenzaprine
Itraconazole
Repaglinide
Cyclophosphamide
Ketoconazole
Retinoic acid
Cyclosporine
Lansoprazole (minor)
Rifampin
Inducers
Carbamazepine
Nelfinavir
Primidone
Sulfadimidine
Dexamethasone
Nevirapine
Progesterone
Sulfinpyrazone
Ethosuximide
Oxcarbazepine
Rifabutin
Troglitazone
Glucocorticoids
Phenobarbital
Rifampin
Griseofulvin
Phenylbutazone
Rofecoxib (minor)
Nafcillin
Phenytoin
St. John’s Wort
44
Inhibitors
Amiodarone
Disulfiram
Mibefradil
Ranitidine
Anastrozole
Entacapone
Miconazole (moderate)
Ritonavir**
Azithromycin
Erythromycin
Nefazodone
Saquinavir
Cannabinoids
Ethenyl estradiol
Nelfinavir
Sertindole
Cimetidine
Fluconazole (weak)
Nevirapine
Sertraline
Clarithromycin
Fluoxetine
Norfloxacin
Troglitazone
Clotrimazole
Fluvoxamine
Norfluoxetine
Troleandomycin
Cyclosporine
Gestodene
Omeprazole (weak)
Valproic acid (weak)
Danazole
Grapefruit Juice
Oxiconazole
Verapamil
Delavirdine
Indinavir
Paroxetine (weak)
Zarfirlukast
Dexamethasone
Isoniazid
Propoxyphene
Zileuton
Dimethyldithiocarbamate
Itraconazole**
Quinidine
Diltiazem
Ketoconazole**
Quinin
Dirithromycin
Metronidazole
Quinupristin and
dalfopristin
** Contraindications
From Drug Information Handbook 8th Edition
| 2 | arm 1: The first stage was to rule out the probability of 4 month progression free survival.
Patients were given 400 mg BAY 43-9006 orally twice daily in 28 day cycles. arm 2: Due to prostatic specific antigen and radiographic discordance during the first stage, the protocol was amended to allow accrual to a second stage.
Patients were given 400 mg BAY 43-9006 orally twice daily in 28 day cycles. | [
0,
0
] | 1 | [
0
] | intervention 1: 400 mg BAY 43-9006 orally twice daily in 28 day cycles. | intervention 1: BAY 43-9006 | 1 | Bethesda | Maryland | United States | -77.10026 | 38.98067 | 46 | 0 | 0 | 0 | NCT00090545 | 1COMPLETED | 2009-04-01 | 2004-09-01 | National Cancer Institute (NCI) | 0NIH | true | false | false | https://cdn.clinicaltrials.gov/large-docs/45/NCT00090545/Prot_000.pdf | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3,
4
] | 190 | RANDOMIZED | PARALLEL | 0TREATMENT | 2DOUBLE | false | 0ALL | true | Maraviroc (UK-427,857), a selective and reversible CCR5 co-receptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients in the United States, maraviroc (UK-427,857) is approved for use as part of combination antiretroviral treatment in treatment-experienced and treatment-naive adult subjects. At least 50% of treatment-experienced patients are infected with R5-tropic HIV-1 exclusively. However, even in patients infected with a dual tropic (R5 + X4) phenotype, a large proportion of the virus population still uses CCR5 exclusively. Thus, the purpose of this study is to evaluate the antiretroviral activity, and safety, of maraviroc (UK-427,857) (in combination with other agents) in HIV infected, treatment experienced patients who are failing their current antiretroviral regimen and not infected with R5-tropic virus exclusively. This study will involve more than 200 centers globally to achieve a total randomized subject population of 192 subjects. Patients will be randomly (1:1:1) assigned to one of three groups: Optimized Background Therapy \[OBT (3-6 drugs based on treatment history and resistance testing)\] + maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone. Randomization was stratified by Enfuvirtide use in OBT (yes/no) and Screening HIV-1 RNA level (viral load) (\<100,000/≥ 100, 000 copies per milliliter \[copies per mL\]). The study will enroll over approximately a 9 month period with 48 weeks of treatment. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 24 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will also be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24 and 48. | (i) Subjects remained on their assigned therapy for 48 weeks, unless the subject was discontinued early for protocol-defined treatment failure or other reasons such as adverse event, loss to follow-up, withdrawal of consent, or death.
(ii) If a subject met the criteria for treatment failure or discontinued for another reason (eg, pregnancy, adverse event) and required an alternative regimen, the subject was followed until the Week 48 visit according to protocol guidelines. The new regimen, selected by the Investigator based on the results of resistance testing at the time of failure, had to be recorded in the CRF.
(iii) Open-label maraviroc (UK-427,857) was provided by the sponsor, until it was commercially available, to subjects who completed 48 weeks of therapy and for whom it was medically appropriate to continue therapy with maraviroc (UK-427,857). | HIV Infections | null | 3 | arm 1: None arm 2: None arm 3: None | [
0,
0,
0
] | 5 | [
0,
0,
0,
0,
0
] | intervention 1: OBT (3-6 drugs based on treatment history and resistance testing) intervention 2: maraviroc (UK-427,857) 150 mg taken once daily intervention 3: OBT (3-6 drugs based on treatment history and resistance testing) intervention 4: maraviroc (UK-427,857) 150 mg taken twice daily intervention 5: OBT (3-6 drugs based on treatment history and resistance testing) | intervention 1: Optimized Background Therapy (OBT) intervention 2: maraviroc (UK-427,857) intervention 3: Optimized Background Therapy (OBT) intervention 4: maraviroc (UK-427,857) intervention 5: Optimized Background Therapy (OBT) | 77 | Birmingham | Alabama | United States | -86.80249 | 33.52066
Phoenix | Arizona | United States | -112.07404 | 33.44838
Beverly Hills | California | United States | -118.40036 | 34.07362
Fountain Valley | California | United States | -117.95367 | 33.70918
Hayward | California | United States | -122.0808 | 37.66882
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Los Angeles | California | United States | -118.24368 | 34.05223
Newport Beach | California | United States | -117.92895 | 33.61891
Oakland | California | United States | -122.2708 | 37.80437
San Francisco | California | United States | -122.41942 | 37.77493
San Francisco | California | United States | -122.41942 | 37.77493
San Francisco | California | United States | -122.41942 | 37.77493
Union City | California | United States | -122.01913 | 37.59577
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Washington D.C. | District of Columbia | United States | -77.03637 | 38.89511
Miami | Florida | United States | -80.19366 | 25.77427
North Miami Beach | Florida | United States | -80.16255 | 25.93315
Orlando | Florida | United States | -81.37924 | 28.53834
Orlando | Florida | United States | -81.37924 | 28.53834
Sarasota | Florida | United States | -82.53065 | 27.33643
Tampa | Florida | United States | -82.45843 | 27.94752
Vero Beach | Florida | United States | -80.39727 | 27.63864
Atlanta | Georgia | United States | -84.38798 | 33.749
Springfield | Massachusetts | United States | -72.58981 | 42.10148
Santa Fe | New Mexico | United States | -105.9378 | 35.68698
Albany | New York | United States | -73.75623 | 42.65258
Brooklyn | New York | United States | -73.94958 | 40.6501
Manhasset | New York | United States | -73.69957 | 40.79788
New York | New York | United States | -74.00597 | 40.71427
Stony Brook | New York | United States | -73.14094 | 40.92565
Stony Brook | New York | United States | -73.14094 | 40.92565
The Bronx | New York | United States | -73.86641 | 40.84985
The Bronx | New York | United States | -73.86641 | 40.84985
Huntersville | North Carolina | United States | -80.84285 | 35.41069
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238
Columbia | South Carolina | United States | -81.03481 | 34.00071
Dallas | Texas | United States | -96.80667 | 32.78306
Dallas | Texas | United States | -96.80667 | 32.78306
Annandale | Virginia | United States | -77.19637 | 38.83039
Puyallup | Washington | United States | -122.2929 | 47.18538
Tacoma | Washington | United States | -122.44429 | 47.25288
Vancouver | Washington | United States | -122.66149 | 45.63873
Darlinghurst | New South Wales | Australia | 151.21925 | -33.87939
Surry Hills | New South Wales | Australia | 151.21282 | -33.88374
Herston | Queensland | Australia | 153.01852 | -27.44453
Carlton | Victoria | Australia | 144.96667 | -37.8
Melbourne | Victoria | Australia | 144.96332 | -37.814
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Brussels | N/A | Belgium | 4.34878 | 50.85045
Liège | N/A | Belgium | 5.56749 | 50.63373
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Toronto | Ontario | Canada | -79.39864 | 43.70643
Toronto | Ontario | Canada | -79.39864 | 43.70643
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Montreal | Quebec | Canada | -73.58781 | 45.50884
Berlin | N/A | Germany | 13.41053 | 52.52437
Cologne | N/A | Germany | 6.95 | 50.93333
Hamburg | N/A | Germany | 9.99302 | 53.55073
Hamburg | N/A | Germany | 9.99302 | 53.55073
Hamburg | N/A | Germany | 9.99302 | 53.55073
Utrecht | N/A | Netherlands | 5.12222 | 52.09083
Elche | Alicante | Spain | -0.70107 | 38.26218
Badalona | Barcelona | Spain | 2.24741 | 41.45004
Barcelona | Barcelona | Spain | 2.15899 | 41.38879
Córdoba | Cordoba | Spain | -4.77275 | 37.89155
Madrid | Madrid | Spain | -3.70256 | 40.4165
Madrid | Madrid | Spain | -3.70256 | 40.4165
Zurich | N/A | Switzerland | 8.55 | 47.36667
Brighton | N/A | United Kingdom | -0.13947 | 50.82838
Edinburgh | N/A | United Kingdom | -3.19648 | 55.95206
London | N/A | United Kingdom | -0.12574 | 51.50853
London | N/A | United Kingdom | -0.12574 | 51.50853 | 186 | 0 | 0 | 0 | NCT00098748 | 1COMPLETED | 2009-04-01 | 2004-11-01 | ViiV Healthcare | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
0
] | 56 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | true | This study will investigate long-term, low-dose growth hormone administration in HIV-infected patients with reduced growth hormone (GH) secretion and increased visceral adiposity. We hypothesize that low-dose growth hormone will reduce visceral fat. Secondary endpoints will include measures of insulin-like growth factor-1 (IGF-1), glucose homeostasis, lipids, blood pressure,bone density, cardiovascular risk and safety parameters. | This study will investigate long-term, low-dose growth hormone administration in HIV-infected patients with reduced growth hormone (GH) secretion and increased visceral adiposity. We hypothesize that low-dose growth hormone will reduce visceral fat preferentially over subcutaneous fat, and increase lean body mass. Secondary endpoints will include measures of IGF-1, glucose homeostasis, lipids, blood pressure,bone density, cardiovascular risk and safety parameters. Dosing of growth hormone will be based on patients' IGF-1 levels and will not exceed 6mcg/kg/day. | AIDS HIV Infections | HIV lipodystrophy growth hormone visceral fat IGF-I Treatment Experienced | null | 2 | arm 1: recombinant human growth hormone subcutaneously once a day arm 2: placebo subcutaneously once a day | [
1,
2
] | 2 | [
0,
0
] | intervention 1: growth hormone dosed by weight and IGF-1 level,subcutaneously once a day, 18 months intervention 2: placebo subcutaneously once a day, 18 months | intervention 1: recombinant human growth hormone intervention 2: placebo | 1 | Boston | Massachusetts | United States | -71.05977 | 42.35843 | 55 | 0 | 0 | 0 | NCT00100698 | 1COMPLETED | 2009-04-01 | 2004-01-01 | Massachusetts General Hospital | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 17 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | false | This study will test whether an experimental drug called Revlimid (lenalidomide) can reduce tumor size and prolong survival in patients with metastatic melanoma (melanoma that has spread beyond the original tumor site). It will also examine the toxicity and blood effects of Revlimid.
Patients 18 years of age and older with stage IV ocular melanoma may be eligible for this study. Candidates are screened with a medical history and physical and examination, blood and urine tests, electrocardiogram, chest x-ray, computed tomography (CT) scan and other imaging scans if needed, such as a bone scan, magnetic resonance imaging (MRI), ultrasound, or positron emission tomography (PET).
Participants are admitted to the National Institutes of Health (NIH) Clinical Center for 24 hours for their first oral dose of Revlimid. During the hospital stay, blood is drawn before the dose is given and again at 0.25, 0.5, 1, 2, 4, 6, 9, 12 and 24 hours after dosing to see how the body handles the drug. If the drug is well tolerated, patients are sent home with a 21-day supply of drug to take once a day for 21 days, then go off drug 7 days. This regimen constitutes one 28-day treatment cycle. Treatment cycles may continue for up to 2 years.
Patients keep a daily diary of side effects and have blood drawn once a week. The drug dose may be adjusted according to the laboratory test results. If unacceptable toxicity occurs, treatment may be stopped.
Patients who agree to be biopsied undergo this procedure before treatment begins and at the end of treatment cycles 3 and 6. A small area of skin is numbed with medicine and a small piece of tumor is removed with a needle or by a small cut in the tumor. The tissue is examined under a microscope.
Patients return to NIH after the first month of treatment and then every 3 months to evaluate their tumors and treatment of side effects. The visits include a physical examination, x-rays and scans to evaluate tumors. Visits are scheduled every 3 months while on treatment; then every 3 months for 2 years afterwards; then every 4 months for 1 year; and as needed after that. Patients will have a brain magnetic resonance imaging scan once a year to watch for new tumor areas. | Background:
* Patients with stage IV ocular melanoma have very few available treatment options and an overall poor prognosis.
* Pre-clinical and early clinical evidence suggest that lenalidomide has activity against solid tumors.
* This trial is designed to evaluate the safety and efficacy of two different doses of a novel antiangiogenic and immunomodulatory agent, lenalidomide (Revlimid ).
Objectives:
Primary Objectives:
* Determine the response rate to lenalidomide at two dose levels for patients with Stage IV ocular melanoma.
* To determine the toxicity of lenalidomide at two dose levels in this setting.
Secondary Objectives:
* To determine the progression free and overall survival of patients with Stage IV ocular melanoma treated with lenalidomide.
* When easily accessible, obtain tissue at baseline and during therapy to evaluate the effects of these agents on pathways, thought to be modulated by lenalidomide in pre-clinical studies.
* To determine the pharmacokinetics of lenalidomide at these two doses in patients with Stage IV ocular melanoma.
* To determine if there is a dose level with potentially superior efficacy and acceptable toxicity.
Eligibility:
* Patients \> 18 years of age with stage IV ocular melanoma, who have measurable disease.
* Patient must be Eastern Cooperative Oncology Group (ECOG) performance status of = 2 and a life expectancy of more than 3 months.
* Patients must have adequate organ function.
* Patients must not have had prior surgery, chemotherapy, hormonal therapy, radiation therapy, or biological therapy for at least 4 weeks prior to starting study medication.
* Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration of chemotherapy.
* Patients must not have an acute, critical illness,.
* All patients who are sexually active and able to conceive will be required to use contraception during treatment with lenalidomide
Design:
* A phase II trial in which patients are randomized to 2 dose levels of lenalidomide administered for 21 days every 28 days for 2 years.
* 76 patients (allowing for up to 3 inevaluable patients per dose level) will be enrolled over 4 to 5 years.
* The objective of the trial will be to determine in each of the two groups of patients (5 mg and 25 mg dose levels) whether, CC5013 is able to be associated with a response rate (partial response (PR) + complete response (CR)) that can rule out 10% (p0=0.10) in favor of an improved response rate of 30% (p1=0.30). | Melanoma | Response Rate Toxicity Progression-Free Survival Overall Survival Pharmacokinetic Ocular Melanoma | null | 2 | arm 1: oral dose (1 capsule) lenalidomide 25 mg per day 7 days a week for 3 weeks arm 2: oral dose (1 capsule) lenalidomide 5 mg per day 7 days a week for 3 weeks | [
0,
0
] | 1 | [
0
] | intervention 1: oral dose (1 capsule) 25 mg per day 7 days a week for cohort 1 oral dose (1 capsule) 5 mg per day 7 days a week for cohort 2 | intervention 1: Revlimid | 1 | Bethesda | Maryland | United States | -77.10026 | 38.98067 | 17 | 0 | 0 | 0 | NCT00109005 | 1COMPLETED | 2009-04-01 | 2005-04-01 | National Cancer Institute (NCI) | 0NIH | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
0
] | 43 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | false | The purpose of this study is to determine whether FDG-PET is capable of detecting atherosclerotic plaque inflammation and monitoring the effects of statins on plaque inflammation. The usefulness of FDG-PET in risk stratification is also investigated. | There is increasing evidence that inflammation plays a role in progression and destabilization of atherosclerotic plaque. However, currently, no non-invasive method is available for detecting plaque inflammation in clinical practice. FDG-PET can visualize activated metabolic levels of not only tumor cells but also inflammatory cells. Thus, it is possible that FDG-PET can detect atherosclerotic plaque inflammation and that, if so, FDG-PET can monitor the direct effect of statins on plaque inflammation. Additionally, monitoring the plaque inflammation by FDG-PET may be useful for determining the risk stratification of atherosclerotic patients.
Originally, we sought to compare patients with FDG-positive plaque with patients with plaque but not with FDG uptake, patients with FDG-positive plaque receiving statin therapy, and patients with FDG-positive plaque receiving diet management therapy. However, because patient number enrolled in the study was too small, the comparison was performed between FDG-positive patients with and without any statin therapy. | Atherosclerosis | atherosclerosis inflammation statins PET carotid ultrasonography | null | 2 | arm 1: Patients with FDG-positive plaque who received simvastatin and diet therapy arm 2: Patients FDG-positive plaque who received diet therapy alone | [
0,
4
] | 1 | [
0
] | intervention 1: simvastatin 5-10 mg/day | intervention 1: simvastatin | 1 | Kurume | N/A | Japan | 130.51667 | 33.31667 | 43 | 0 | 0 | 0 | NCT00114504 | 1COMPLETED | 2009-04-01 | 2004-09-01 | Kurume University | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 20 | RANDOMIZED | PARALLEL | 0TREATMENT | 3TRIPLE | false | 0ALL | true | The purpose of this study is to determine whether left ventricular function improves more rapidly with deferoxamine (DFO) and deferiprone (L1) combination therapy than with DFO monotherapy in patients with thalassemia and decreased ejection fractions. Secondary aims include evaluating changes in myocardial iron burden using T2\* and estimating the relative incidence and severity of chelator-induced toxicity. | DESIGN NARRATIVE:
Participants will be randomized to 1 year of treatment with L1/DFO combination therapy or DFO monotherapy. At baseline, 6 months, and 1 year on therapy, cardiac function will be assessed by MRI measurement of left ventricular ejection fraction (LVEF), T2\*, Holter monitoring, and electrocardiography. Additional monitoring for safety includes weekly blood testing, monthly visits, and periodic eye and ear exams. | Cardiovascular Diseases Heart Diseases Beta-Thalassemia | null | 2 | arm 1: Deferoxamine (DFO) and deferiprone (L1) combination therapy arm 2: Deferoxamine (DFO) monotherapy | [
0,
1
] | 2 | [
0,
0
] | intervention 1: Deferoxamine will be given daily for 12-24h/day 7 days a week either subcutaneous or intravenous at up to 50-60 mg/kg/day. intervention 2: The dose of L1, 75mg/kg in three divided oral doses, is the maximum dose at which toxicity has been tested in prospective trials | intervention 1: Deferoxamine intervention 2: Deferiprone (L1) | 6 | Los Angeles | California | United States | -118.24368 | 34.05223
Oakland | California | United States | -122.2708 | 37.80437
Chicago | Illinois | United States | -87.65005 | 41.85003
Boston | Massachusetts | United States | -71.05977 | 42.35843
New York | New York | United States | -74.00597 | 40.71427
Philadelphia | Pennsylvania | United States | -75.16362 | 39.95238 | 20 | 0 | 0 | 0 | NCT00115349 | 6TERMINATED | 2009-04-01 | 2005-06-01 | Carelon Research | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
3
] | 435 | RANDOMIZED | PARALLEL | 0TREATMENT | 0NONE | false | 0ALL | null | This 2-arm study evaluated the efficacy and safety of 2 different treatment schedules of oral Xeloda with intravenous (IV) Eloxatin (oxaliplatin) and IV bevacizumab (Avastin) as a first-line treatment in patients with locally advanced or metastatic colorectal cancer. Patients were randomized to receive either: 1) Xeloda 850 mg/m\^2 orally twice a day (po bid) on Days 1-14, oxaliplatin 130 mg/m\^2 IV on Day 1, and Avastin 7.5 mg/kg IV on Day 1 of each 3-week cycle; or 2) Xeloda 1500 mg/m\^2 po bid on Days 1-7, oxaliplatin 85 mg/m\^2 IV on Day 1 and Avastin 5 mg/kg IV on Day 1 of each 2-week cycle. The anticipated time on study treatment was 1-2 years, and the target sample size was 100-500 individuals. | null | Colorectal Cancer | null | 2 | arm 1: None arm 2: None | [
0,
1
] | 6 | [
0,
0,
0,
0,
0,
0
] | intervention 1: 850 mg/m\^2 po bid on Days 1-14 of each 3-week cycle intervention 2: 130 mg/m\^2 IV on Day 1 of each 3-week cycle intervention 3: 7.5 mg/kg IV on Day 1 of each 3-week cycle intervention 4: 1500 mg/m\^2 po bid on Days 1-7 of each 2-week cycle intervention 5: 85 mg/m\^2 IV on Day 1 of each 2-week cycle intervention 6: 5 mg/kg IV on Day 1 of each 2-week cycle | intervention 1: capecitabine intervention 2: Oxaliplatin intervention 3: bevacizumab intervention 4: capecitabine intervention 5: Oxaliplatin intervention 6: bevacizumab | 0 | null | 419 | 0 | 0 | 0 | NCT00118755 | 1COMPLETED | 2009-04-01 | 2005-07-01 | Hoffmann-La Roche | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
3
] | 27 | RANDOMIZED | PARALLEL | 1PREVENTION | 3TRIPLE | false | 0ALL | true | Children with sickle cell anemia (SCA) seem to have higher energy needs than children who do not have the disease. This may be the reason why children and teenagers with sickle cell anemia tend to be smaller, weigh less, and have less fat and muscle than children and teens that do not have the disease.
This study is being done to find out if giving a supplement called glutamine will help children with sickle cell anemia by lowering their energy needs and improving their growth and strength. Children will be randomly assigned (like a flip of a coin) to one of two groups. One group will take glutamine and one group will take a placebo (a protein mixture that looks like glutamine but may not have the same effect in the body). No one will know which group is taking which supplement until the study has been completed. Children will be in the study for 12 months. | 1. The study will compare the effect of glutamine and placebo on resting energy expenditure (REE) in children with sickle cell anemia (SCA) by comparing the change in REE ratio between baseline and 12 months.
2. The study investigates the effect of oral glutamine and placebo on body composition in children with SCA by comparing the difference in body mass indexes (BMIs) and percent of body fat (DEXA Scan) between baseline and 12 months of treatment in the two groups.
3. This Study will investigate the effect of oral glutamine and placebo on growth in children with SCA by comparing the Z scores for one year before baseline to 1 year while on study.
4. This study will investigate the effect of oral glutamine and placebo in children with SCA by comparing the difference in the levels of plasma and red blood cell glutamine between baseline and 12 months of treatment in the two groups.
5. This study will investigate the clinical effects (strength and exercise endurance) of oral glutamine and placebo in children with SCA by comparing the difference between baseline and 12 months of treatment in the two groups.
6. This study will evaluate quality of life in children with SCA who have glutamine or placebo for 12 months.
7. This study will evaluate the changes in REE over time in a small group of patients that will have REE measurement at months 3, 6, and 9. This objective will be offered to all patients, but will be "additional studies" that are not required to participate in the protocol. | Anemia, Sickle Cell | Hemoglobin S Disease Sickle Cell Anemia | null | 2 | arm 1: Glutamine arm 2: None | [
0,
2
] | 2 | [
0,
0
] | intervention 1: 0.6 gm/kg of oral glutamine per day, in two doses for one year. intervention 2: Placebo | intervention 1: Glutamine intervention 2: Placebo | 1 | Memphis | Tennessee | United States | -90.04898 | 35.14953 | 25 | 0 | 0 | 0 | NCT00131508 | 6TERMINATED | 2009-04-01 | 2004-05-01 | St. Jude Children's Research Hospital | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 147 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | false | A well-known side-effect of cytostatics (drugs against malignancies) is a decrease in the number of white blood cells, especially of the so-called neutrophil granulocytes, which are very important for the defense against infections. Hence their decrease (called "neutropenia") leads to a predisposition to infections.
Since infections during neutropenia can be very dangerous, the patients are treated with antibiotics from the very first signs of such an infection (usually fever). If the antibiotics (drugs against bacteria) do not lead to a normalization of the body temperature within four days, a drug against fungi is added.
In the IDEA study, one half of the patients receive the antifungal drug voriconazole (as usual) only in case the antibiotics alone do not lead to a normalization of the body temperature (current standard of care). The other half of the patients receive voriconazole immediately after onset of fever (concomitantly with the antibiotics).
The research question is, whether in the "early-treatment" group fewer manifest fungal infections will be observed than in the "late-treatment" group. | null | Possible Fungal Infection | Neutropenia Fever of unknown origin Empirical treatment Voriconazole | null | 2 | arm 1: Voriconazole starts within 18 hours of onset of fever intravenously with a loading dose of 6 mg/kg q12h for the first two doses followed by 4 mg/kg q12h (maintenance dose). Switched to oral treatment (200 mg BID) is possible after at least four days. Treatment will be ended if the patient is afebrile (\< 38.0 °C) for 7 days with neutrophil counts \< 500/µL, or if the patient is afebrile (\< 38.0 °C) for 2 days with neutrophil counts \> 500/µL. arm 2: Treatment with voriconazole (for dosage see "early treatment arm") is initiated only if a patient is persistently febrile on day 5 after the onset of fever despite antibiotic treatment. | [
0,
5
] | 2 | [
0,
0
] | intervention 1: voriconazole, early treatment intervention 2: voriconazole, deferred treatment | intervention 1: voriconazole (Vfend) intervention 2: voriconazole (Vfend) | 28 | Augsburg | N/A | Germany | 10.89851 | 48.37154
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Berlin | N/A | Germany | 13.41053 | 52.52437
Bielefeld | N/A | Germany | 8.53333 | 52.03333
Bremen | N/A | Germany | 8.80717 | 53.07582
Chemnitz | N/A | Germany | 12.92922 | 50.8357
Cologne | N/A | Germany | 6.95 | 50.93333
Dresden | N/A | Germany | 13.73832 | 51.05089
Erlangen | N/A | Germany | 11.00783 | 49.59099
Essen | N/A | Germany | 7.01228 | 51.45657
Frankfurt (Oder) | N/A | Germany | 14.55062 | 52.34714
Freiburg im Breisgau | N/A | Germany | 7.85222 | 47.9959
Göttingen | N/A | Germany | 9.93228 | 51.53443
Hanover | N/A | Germany | 9.73322 | 52.37052
Homburg/Saar | N/A | Germany | N/A | N/A
Kiel | N/A | Germany | 10.13489 | 54.32133
Leipzig | N/A | Germany | 12.37129 | 51.33962
Ludwigshafen | N/A | Germany | 9.06138 | 47.81663
Lübeck | N/A | Germany | 10.68729 | 53.86893
Mainz | N/A | Germany | 8.2791 | 49.98419
München | N/A | Germany | 13.31243 | 51.60698
München | N/A | Germany | 13.31243 | 51.60698
Potsdam | N/A | Germany | 13.06566 | 52.39886
Stuttgart | N/A | Germany | 9.17702 | 48.78232
Trier | N/A | Germany | 6.63935 | 49.75565
Wiesbaden | N/A | Germany | 8.24932 | 50.08258
Würzburg | N/A | Germany | 9.95121 | 49.79391 | 147 | 0 | 0 | 0 | NCT00150345 | 1COMPLETED | 2009-04-01 | 2005-01-01 | Pfizer | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
3
] | 36 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | false | Thirty-six subjects with hyperlipidemia and metabolic syndrome and/or diabetes were randomized in a double-blind manner to either pravastatin 80 mg or atorvastatin 10 mg daily. Oxidative stress (dROMs assay that measures lipid hydroperoxides, plasma thiobarbituric acid reactive substances \[TBARS\], and aminothiol levels) and brachial artery flow-mediated dilation (FMD) were measured at baseline and after 12 weeks of statin therapy. | Individuals with a high cholesterol level, diabetes or metabolic syndrome (collection of abnormalities such as high blood pressure, high triglyceride levels \[fat\], obesity, high blood glucose level) have an increased risk of developing a hardening of the arteries and heart disease.
A group of medications called statins, commonly used worldwide to lower cholesterol levels, are known to reduce the risk of heart disease through their effects on reducing cholesterol levels. These medications also have effects beyond the lowering of cholesterol that may help mediate their beneficial effects on the heart and blood vessels.
These include a reduced production of molecules that harm the arteries such as reactive oxygen species (ROS) and increasing the number of stem cells that help repair vessels, called endothelial progenitor cells (EPCs).
Recent studies have shown that different statins might have different effects on protecting people from developing heart disease. These differences may be due to differences in these non-cholesterol lowering processes, and are the subject of this study.
Standard of Care:
The two statins that will be used in this study, pravastatin (Pravachol ®) and atorvastatin (Lipitor®), are approved for use in people with a high cholesterol level or heart disease. These medications are generally very well tolerated with minimal side effects. They are not approved for use in patients to increase the level of EPCs or to reduce the production of ROS, and therefore are considered experimental for this indication. Currently there are no drugs that are specifically approved for these indications.
How the Problem Will be Studied:
These statins will be given to patients who have high cholesterol and either diabetes or the metabolic syndrome once a day for 12 weeks. We, the investigators at Emory, will measure the level of EPCs and ROS before and during the administration of the statin. We will also investigate how well the blood vessels dilate in response to these medications by performing an imaging study of the forearm artery using ultrasound.
The study is blinded and there is an equal chance of receiving either atorvastatin 10mg or pravastatin 80mg which are likely to lower cholesterol level by a similar amount.
How Research Will Advance Scientific Knowledge:
The goal of this study is to determine if atorvastatin will increase the number of circulating EPCs and reduce the production of ROS more than pravastatin. This may help explain the differences between these drugs that have been observed in some recently published trials. | Diabetes Mellitus Metabolic Syndrome X Hypercholesterolemia | null | 2 | arm 1: None arm 2: None | [
0,
0
] | 2 | [
0,
0
] | intervention 1: 12 Weeks of Oral Atorvastatin 10 mg therapy. intervention 2: 12 Weeks of Oral Pravastatin 80 mg therapy. | intervention 1: Atorvastatin intervention 2: Pravastatin | 1 | Atlanta | Georgia | United States | -84.38798 | 33.749 | 36 | 0 | 0 | 0 | NCT00166036 | 1COMPLETED | 2009-04-01 | 2004-09-01 | Emory University | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
4
] | 57 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | false | To estimate the percentage of children with serum IGF-1 \> 2 standard deviation (compared to a child of the same gender and age and without growth hormone (GH) deficiency) 9 months and 12 months after initiation of GH treatment. | null | Fetal Growth Retardation | null | 1 | arm 1: None | [
0
] | 1 | [
0
] | intervention 1: 0.40 mg/kg/week dived in 7 daily subcutaneous injections during 2 years | intervention 1: Genotonorm (Somatropin) | 22 | Amiens | N/A | France | 2.3 | 49.9
Angers | N/A | France | -0.55202 | 47.47156
Besançon | N/A | France | 6.01815 | 47.24878
Bordeaux | N/A | France | -0.5805 | 44.84044
Bron | N/A | France | 4.91303 | 45.73865
Caen | N/A | France | -0.35912 | 49.18585
Dunkirk | N/A | France | 2.37681 | 51.0344
Lille | N/A | France | 3.05858 | 50.63297
Limoges | N/A | France | 1.24759 | 45.83362
Lorient | N/A | France | -3.37177 | 47.74817
Nice | N/A | France | 7.26608 | 43.70313
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Paris | N/A | France | 2.3488 | 48.85341
Rennes | N/A | France | -1.67429 | 48.11198
Rouen | N/A | France | 1.09932 | 49.44313
Strasbourg | N/A | France | 7.74553 | 48.58392
Tarbes | N/A | France | 0.07139 | 43.23407
Toulouse | N/A | France | 1.44367 | 43.60426
Toulouse | N/A | France | 1.44367 | 43.60426
Tours | N/A | France | 0.70398 | 47.39484
Vandœuvre-lès-Nancy | N/A | France | 6.17114 | 48.66115 | 57 | 0 | 0 | 0 | NCT00174252 | 1COMPLETED | 2009-04-01 | 2005-02-01 | Pfizer | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
[
5
] | 30 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | true | This is an 8-week open-label study aimed at assessing the effectiveness and tolerability of Quetiapine, in the treatment of preschool children aged 4 to 6 years with bipolar and bipolar spectrum disorder. This is an exploratory, pilot study, seeking to determine whether Quetiapine is efficacious and well tolerated in the treatment of preschoolers with pediatric bipolar and bipolar spectrum disorder in this age group. The study results will be used to generate hypotheses for a larger randomized controlled clinical trial with explicit hypotheses and sufficient statistical power. | Seroquel is a psychotropic agent that affects multiple neurotransmitter receptors in the brain: serotonin 5HT1A and 5HT2, dopamine D1 and D2, histamine H1 (IC50=30nM), and adrenergic receptors.
This is an 8-week open-label study aimed at assessing the effectiveness and tolerability of Quetiapine, in the treatment of preschool children aged 4 to 6 years with bipolar and bipolar spectrum disorder. This is an exploratory, pilot study, seeking to determine whether Quetiapine is efficacious and well tolerated in the treatment of preschoolers with pediatric bipolar and bipolar spectrum disorder in this age group. The study results will be used to generate hypotheses for a larger randomized controlled clinical trial with explicit hypotheses and sufficient statistical power. | Bipolar Disorder Mania | children bipolar disorder quetiapine preschoolers | null | 1 | arm 1: 2.5 - 5.0mg/kg PO BID quetiapine
Other Names:
Seroquel | [
0
] | 1 | [
0
] | intervention 1: 2.5 - 5.0mg/kg PO BID quetiapine | intervention 1: quetiapine | 0 | null | 30 | 0 | 0 | 0 | NCT00181883 | 1COMPLETED | 2009-04-01 | 2005-02-01 | Massachusetts General Hospital | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 86 | RANDOMIZED | PARALLEL | 0TREATMENT | 4QUADRUPLE | false | 0ALL | true | This study will compare two different antidepressant treatment regimens to determine which is more effective in reducing symptoms of bipolar depression. | Depression is a serious condition that is often difficult to diagnosis and treat. Bipolar disorder-related depression is especially complex because of the presence of mania symptoms. Lamotrigine and divalproex are commonly prescribed medications for depression. However, their effectiveness in treating bipolar depression has not been thoroughly evaluated. Studies have shown that combining lamotrigine with another antidepressant may be more effective in reducing depressive symptoms than lamotrigine alone. This study will provide participants with either lamotrigine alone or in combination with divalproex and will determine which regimen is more effective in reducing symptoms of bipolar depression.
Participants will be randomly assigned to a daily regimen of either lamotrigine and divalproex or lamotrigine and placebo for 8 months. Participants will be assessed at study entry, at two unspecified times during the study, and at the end of the study. During each assessment, participants will undergo a brief interview and complete a questionnaire about their depressive symptoms, any physical manifestations of their depression, and their overall level of functioning in daily activities. | Bipolar Disorder Depression | Lamotrigine Divalproex Antidepressant | null | 2 | arm 1: Participants will take active lamotrigine and active divalproex ER arm 2: Participants will take active lamotrigine and placebo | [
1,
2
] | 3 | [
0,
0,
0
] | intervention 1: If the participant is naive to LAM, LAM will be started at 25 mg every day for the first 2 weeks, then 50 mg per day for the next 2 weeks. The dose of LAM can be increased to 100 mg at week 5 and increased to maximum of 200 mg at week 6 based on symptoms, tolerability, and ratings of the rating scales. If the participant is already taking LAM, the dose will be increased to up to 200 mg using the same guide lines. Upon randomization the participant in the placebo comparator will have their dosage titrated to doubled since the potentiating effect of the Divalproex will no longer exist. It will remain at this dosage until the end of the study with the possibility of one adjustment for side effects. intervention 2: If the participant is naive to DIV and if LAM was initiated before the start of treatment with DIV, DIV can be started at any point of time in the study provided the participant has been on LAM for at least 2 weeks. DIV will be started at 500 mg and titrated by increments of 500 mg every 3 to 4 days until a therapeutic blood level is attained up to 2500 mg. intervention 3: During the randomized phase participants randomized to placebo comparator group will discontinue DIV and will start taking the placebo in the same fashion. | intervention 1: Lamotrigine intervention 2: Divalproex (DIV) ER intervention 3: Placebo | 0 | null | 86 | 0 | 0 | 0 | NCT00183469 | 1COMPLETED | 2009-04-01 | 2004-12-01 | The University of Texas Health Science Center at San Antonio | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
5
] | 17 | NA | SINGLE_GROUP | 0TREATMENT | 0NONE | true | 0ALL | false | Latanoprost is a commonly used treatment for glaucoma. Because of its mechanism of action, it is plausible that the age of a patient using the medication may affect its efficacy and time of onset.
We are going to study the effectiveness of Latanoprost in people of different ages, to see if it changes based on the age of the patient. | Latanoprost is a topical ocular hypotensive medication with a well established safety and efficacy profile. Its effect is mediated by an increase in uveoscleral outflow, due to enzymatic degradation of the extracellular matrix within the ciliary muscle. Since the amount of extracellular matrix within the human eye increases with age, and uveoscleral outflow decreases with age, it would be expected that there should be a difference in the efficacy of latanoprost in patients of different ages. This has not been demonstrated in studies assessing the overall effect of latanoprost across adult age groups using multivariate analysis. (Camras CB et al, 1996).
However, a difference in timing of onset of drug effect may get overlooked in clinical studies and in clinical practice as well, as patients tend to be seen from two to eight weeks after initiation of treatment, by which time any differences in response time may have already occurred and leveled off.
To our knowledge, there are no studies specifically looking at the timing of onset of drug effect of latanoprost in different age groups. Because of the theoretical plausibility of this effect based on the mechanism of action of latanoprost, this represents an opportunity to further elucidate the characteristics of this medication in a manner which has clinical and scientific relevance.
Our aim is thus to determine if there is a difference in timing of onset of the ocular hypotensive effect of latanoprost in glaucoma patients of different age groups. | Glaucoma | Latanoprost Glaucoma Intraocular pressure | null | 1 | arm 1: All participants will be taking Latanoprost; This study compares efficacy within age groups. | [
5
] | 1 | [
0
] | intervention 1: Latanoprost 0.005% ophthalmic solution QHS 8 weeks | intervention 1: Latanoprost 0.005% | 1 | New Haven | Connecticut | United States | -72.92816 | 41.30815 | 17 | 0 | 0 | 0 | NCT00224289 | 1COMPLETED | 2009-04-01 | 2005-03-01 | Yale University | 7OTHER | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
[
4
] | 112 | NON_RANDOMIZED | SINGLE_GROUP | 0TREATMENT | 0NONE | false | 0ALL | true | The purpose of this study is to examine the long-term safety and tolerability of human corticotropin-releasing factor (hCRF), XERECEPT®, in patients requiring dexamethasone (Decadron) to treat peritumoral brain edema. This open-label, extended-use study is open to all patients who participate in either of the blinded studies, NTI 0302, NTI 0303, or other designated studies, including patients who may have discontinued blinded study medication early but completed the protocol-stipulated follow-up periods. | XERECEPT® is not a potential treatment for cancer, but may reduce the edema associated with tumors and as a result, decrease neurological symptoms. | Brain Edema Brain Tumor | peritumoral brain edema edema malignant brain tumor astrocytoma brain tumor dexamethasone Decadron | null | 1 | arm 1: All patients will receive hCRF (XERECEPT) 2mg/day | [
0
] | 1 | [
0
] | intervention 1: 2mg/day | intervention 1: hCRF [XERECEPT (corticorelin acetate injection)] | 32 | Phoenix | Arizona | United States | -112.07404 | 33.44838
Newport Beach | California | United States | -117.92895 | 33.61891
Palo Alto | California | United States | -122.14302 | 37.44188
Sacramento | California | United States | -121.4944 | 38.58157
San Diego | California | United States | -117.16472 | 32.71571
Aurora | Colorado | United States | -104.83192 | 39.72943
Englewood | Colorado | United States | -104.98776 | 39.64777
Jacksonville | Florida | United States | -81.65565 | 30.33218
Orlando | Florida | United States | -81.37924 | 28.53834
Tampa | Florida | United States | -82.45843 | 27.94752
Atlanta | Georgia | United States | -84.38798 | 33.749
Chicago | Illinois | United States | -87.65005 | 41.85003
Evanston | Illinois | United States | -87.69006 | 42.04114
Boston | Massachusetts | United States | -71.05977 | 42.35843
Detroit | Michigan | United States | -83.04575 | 42.33143
Amherst | New York | United States | -78.79976 | 42.97839
New York | New York | United States | -74.00597 | 40.71427
New York | New York | United States | -74.00597 | 40.71427
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Cincinnati | Ohio | United States | -84.51439 | 39.12711
Columbus | Ohio | United States | -82.99879 | 39.96118
Portland | Oregon | United States | -122.67621 | 45.52345
Seattle | Washington | United States | -122.33207 | 47.60621
Madison | Wisconsin | United States | -89.40123 | 43.07305
Milwaukee | Wisconsin | United States | -87.90647 | 43.0389
Edmonton | Alberta | Canada | -113.46871 | 53.55014
Winnipeg | Manitoba | Canada | -97.14704 | 49.8844
Moncton | New Brunswick | Canada | -64.7965 | 46.09454
Halifax | Nova Scotia | Canada | -63.57688 | 44.64269
Kingston | Ontario | Canada | -76.48098 | 44.22976
Ottawa | Ontario | Canada | -75.69812 | 45.41117
Toronto | Ontario | Canada | -79.39864 | 43.70643 | 112 | 0 | 0 | 0 | NCT00226655 | 1COMPLETED | 2009-04-01 | 2005-07-01 | Celtic Pharma Development Services | 4INDUSTRY | false | false | false | null | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
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