sssohrab/ct-dosing-errors-benchmark · Datasets at Hugging Face

[ 4 ]

1,029

NON_RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

true

Objective and subjective musculoskeletal evaluations will be performed to determine differences in the ciprofloxacin versus non-quinolone treated pediatric patients so that we can tell what the natural occurrence of such musculoskeletal conditions is in the general pediatric population.

This study is classified as "interventional" due to study-specific medical examinations and interventions. Regarding the study drug intake, routine administration is observed only, there is no intervention in study drug administration.

Infectious Diseases

Pediatrics Safety Musculoskeletal System Neurologic Manifestations Joint Diseases Joint Deformities, Acquired

null

2

arm 1: Subjects receiving Ciprofloxacin (group followed-up for 5 years) arm 2: Subjects receiving non-quinolone antibiotic (group followed-up for 2 years)

[ 0, 1 ]

2

[ 0, 0 ]

intervention 1: Either as oral suspension, oral tablets or sequential intravenous (IV) - oral therapy or purely IV therapy according to label intervention 2: Common used dose and route

intervention 1: Ciprofloxacin intervention 2: Non-quinolone antibiotic

67

0

NCT00761462

[ 5 ]

203

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

true

0ALL

false

Randomized, placebo-controlled, double blind study. 203 subjects entered the study to compare the effect on occasional constipation of polyethylene glycol 3350 to placebo. Subjects took one of study treatments up to 7 days.

null

Constipation

Human Experimentation

null

2

arm 1: MiraLAX® (polyethylene glycol 3350 powder for solution) arm 2: MALTRIN 500® M500 (maltodextrin 500)

[ 1, 2 ]

2

[ 0, 10 ]

intervention 1: Polyethylene glycol 3350 powder for solution. Single dose (17 grams in 4 to 8 ounces of beverage) for 7 days. intervention 2: Maltodextrin 500 powder for solution, One single dose (one capful) in any 4 - 8 ounces beverage for 7 days.

intervention 1: Polyethylene glycol 3350 intervention 2: Placebo, maltodextrin 500 powder for solution

0

null

0

NCT00770432

[ 5 ]

58

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

false

The purpose of the study is to compare the efficacy and safety of Clobetasol propionate to that of its Vehicle in the treatment of mild to moderate plaque-type psoriasis.

The purpose of the study is to compare the efficacy and safety of Clobetasol propionate to that of its Vehicle in the treatment of mild to moderate plaque-type psoriasis. This is a multi-center, double blind, randomized, parallel designed study which consists of 2 weeks of treatment and a follow-up visit 2 weeks later.

Psoriasis

Psoriasis Plaque Type Psoriasis

null

2

arm 1: Topical foam formulation that includes clobetasol propionate (Steroid) arm 2: Vehicle foam is the same as the clobetasol propionate foam except it does not include the active drug.

[ 0, 2 ]

2

[ 0, 0 ]

intervention 1: Topical Clobetasol propionate foam intervention 2: Vehicle foam does not include the active drug.

intervention 1: Clobetasol propionate foam intervention 2: Vehicle foam

2

0

NCT00842153

[ 5 ]

59

RANDOMIZED

CROSSOVER

0TREATMENT

3TRIPLE

false

0ALL

null

This is a single-centre, randomised, double-blind, four-period, incomplete block, crossover study, with 8 days repeat dosing of intranasal Fluticasone Propionate (25, 50, 100, 200ug) and/or placebo in the Vienna Challenge Chamber in subjects with allergic rhinitis.

null

Rhinitis, Allergic, Perennial Allergic Rhinitis

fluticasone propionate Vienna Challenge Chamber glucocorticosteroids allergic rhinitis

null

5

arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None

[ 2, 0, 0, 0, 0 ]

2

[ 0, 0 ]

intervention 1: Corticosteriod, with anti-inflammatory effects intervention 2: Placebo comparator

intervention 1: Fluticasone propionate intervention 2: Placebo

1

Vienna | N/A | Austria | 16.37208 | 48.20849

0

NCT00848965

[ 3 ]

21

RANDOMIZED

CROSSOVER

0TREATMENT

0NONE

false

2MALE

false

Testosterone replacement treatment is the most effective way of treating hypogonadism in men. Acrux has a propriety testosterone replacement product, Testosterone MD-Lotion and this study will evaluate pharmacokinetics of testosterone MD-Lotion formulations.The study will also assess safety of the product.

null

Hypogonadism

null

4

arm 1: Applied once daily for 7 days to both axilla (1.5 mL to each axilla). All study participants are randomized to each of the 4 study treatments. arm 2: Applied once daily for 7 days to one axilla. All study participants are randomized to each of the 4 study treatments. arm 3: Applied once daily for 7 days to both axilla (1.5 mL to each axilla). All study participants are randomized to each of the 4 study treatments. arm 4: Applied once daily for 7 days by three doses to both axilla (2 x 1.5 mL to one axilla and 1 x 1.5 mL to the other axilla). All study participants are randomized to each of the 4 study treatments.

[ 0, 0, 0, 0 ]

1

[ 0 ]

intervention 1: Administered Topically

intervention 1: Testosterone MD-Lotion

4

0

NCT00857961

[ 2 ]

18

RANDOMIZED

PARALLEL

7BASIC_SCIENCE

4QUADRUPLE

true

0ALL

false

This study will characterize the pharmacokinetics of colchicine after an oral dosing regimen of 4.8 mg over 6 hours. In addition it will compare the electrocardiogram (ECG) changes, if any, from this dosing regimen to that of a single dose of moxifloxacin 400 mg, a positive control for the corrected QT interval (QTc) prolongation.

This study will characterize the pharmacokinetics of colchicine after an oral dosing regimen of 4.8 mg over 6 hours. In addition, it will determine whether or not there is a trend toward effect of this high dose regimen on the electrocardiogram (ECG), mainly the corrected QT interval (QTc), via comparison to a 400 mg dose of moxifloxacin, a positive control for QTc prolongation. Eighteen healthy, non-smoking, non-obese, non-pregnant adults between the ages of 18 to 55 years of age will be randomized in a double blind fashion to either the colchicine or moxifloxacin treatment groups. On the day prior to the study (Day -1), subjects will receive colchicine and moxifloxacin placebos according to the same schedule and conditions as will be present during the study, and baseline ECG's will be determined by 24 hour 12-lead Holter monitoring. On Day 1, after a minimum 10 hour overnight fast, subjects enrolled in the colchicine treatment group (N=15) will receive two 0.6 mg capsules (plus one dose moxifloxacin placebo) followed by an additional 0.6 mg colchicine dose (plus one dose moxifloxacin placebo) every hour for 6 additional doses; subjects in the moxifloxacin treatment group will receive placebo doses matching the colchicine treatment group over the first 5 hours, then 400 mg moxifloxacin (plus one dose colchicine placebo) at the 6 hour point. Fasting will continue for 4 hours after the first dose at which time a standardized meal will be served. Blood will be drawn from all participants at times sufficient to adequately define the pharmacokinetics of colchicine. During the study, continuous 24-hour ECG monitoring via 12-lead Holter monitor will be performed. Triplicate ECG records will be extracted from 5 minute observation periods throughout the 24 hours post dose. Finally, all study subjects will be monitored for adverse effects throughout the entire study period.

Pharmacokinetics

healthy

null

2

arm 1: None arm 2: None

[ 0, 1 ]

2

[ 0, 0 ]

intervention 1: two 0.6 mg capsules (1.2 mg dose) followed by an additional 0.6mg capsule every hour for 6 additional doses intervention 2: 400 mg capsule at the 6 hour point

intervention 1: Colchicine intervention 2: Moxifloxacin

1

Fargo | North Dakota | United States | -96.7898 | 46.87719

0

NCT01018420

[ 3, 4 ]

70

NON_RANDOMIZED

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

null

The purpose of this study is to assess the safety and the effects on liver iron of Deferasirox when given for a long treatment period in patients with transfusion dependent iron overload.

null

Liver Iron Overload

iron overload iron chelation therapy B-thalassemia

null

2

arm 1: Deferasirox group consists of all participants who were initially randomized to 10 and 20 mg/kg/day deferasirox orally daily in the main study and remained on the same treatment during the comparative prolongation study (NCT00379483) and at the beginning of the 5-year non-comparative study arm 2: Deferasirox Crossover group consists of participants who were initially randomized to 40 mg/kg/day deferoxamine (DFO)subcutaneously in the main study and comparative prolongation study and crossed over to 5mg/kg/day to 30 mg/kg/day deferasirox orally daily at the beginning of the 5-year non-comparative extension study

[ 0, 0 ]

2

[ 0, 0 ]

intervention 1: 10 mg/kg or 30 mg/kg orally daily intervention 2: 5 mg/kg or 30 mg/kg orally daily

intervention 1: Deferasirox intervention 2: Deferasirox

4

Cagliari | N/A | Italy | 9.11917 | 39.23054 Genova | N/A | Italy | 11.87211 | 45.21604 Milan | N/A | Italy | 9.18951 | 45.46427 Torino | N/A | Italy | 11.99138 | 44.88856

0

NCT01033747

[ 2, 3 ]

7

NON_RANDOMIZED

SINGLE_GROUP

0TREATMENT

0NONE

false

2MALE

false

The purpose of this study is to determine whether thalidomide is effective in the refractory epilepsy treatment.

Seven male patients with chronic, refractory epilepsy were included in the present study; in all cases antiepileptic treatment with multiple antiepileptic drugs had been unsuccessful in reducing the frequency or the intensity of seizures. Patients selected for this study were all males due to the high risk of thalidomide for teratogenicity in pregnant women; besides this drawback, thalidomide presents a fair tolerance profile in humans treated with low doses. Informed consent was obtained on each case by the patient and his legal guardian. The protocol was approved by the committees of research and ethics. Treatment with thalidomide at 200 mg dosage twice daily was administered during a twelve month period. Electroencephalograms were obtained prior and at six months of thalidomide therapy; number and intensity of seizures were individually recorded in a diary by a caregiver (in most cases the patient's mother); signs of neuropathy, a frequent side-effect of chronic thalidomide therapy, were evaluated along the treatment; drowsiness and sedation, which are also common side-effects, were also recorded. Patients were seen once a week during the treatment period at the Epilepsy Clinic of the National Institute of Neurology and Neurosurgery of Mexico. Once informed consent was obtained, all patients were given seizure diaries to be filled for three months before starting the treatment with thalidomide. Comparisons in the frequency of seizures were made on each patient by contrasting the three months previous to the beginning of thalidomide therapy with the twelve months of the drug trial. One patient (case 6) withdrew from the trial after seven months of thalidomide therapy due to sedation. Another patient (case 7) withdrew from the trial after 3 months of treatment due to exacerbation of seizures as narrated by his mother. The same schedule of antiepileptic therapy was taken by each patient during three months prior to thalidomide administration and continued it without modification along the trial; therefore, bias due to changes in the associated antiepileptic medications were prevented and each patient served as his own control; so that the effect of thalidomide on the frequency and intensity of seizures could be reasonably evaluated. Thalidomide was purchased by the National Institute of Neurology and Neurosurgery of Mexico at regular price in the pharmaceutical market. No pharmaceutical company participated in any form in this trial.

Refractory Epilepsy

Thalidomide Antiepileptic drugs Refractory epilepsy Sedative drugs

null

1

arm 1: Open-labeled preliminary trial

[ 0 ]

1

[ 0 ]

intervention 1: Thalidomide at 200 mg dosage bid was administered during a twelve month period.

intervention 1: 3-phthalimidoglutarimide (Thalidomide)

0

null

0

NCT01061866

[ 2 ]

84

RANDOMIZED

CROSSOVER

null

0NONE

true

0ALL

false

The purpose of this study is to assess the bioequivalence of a new oxycodone formulation (80 mg) relative to the original OxyContin® (OXY) formulation (80 mg) in the fasted state.

Oxycodone hydrochloride (oxycodone) is a semi-synthetic opioid analgesic that is effective in the relief of moderate to severe malignant and non-malignant pain.

Healthy

Healthy subjects Opioid Healthy volunteers

null

2

arm 1: Reformulated OXY 80 mg x 1 dose arm 2: Original OxyContin® (OXY) 80 mg x 1 dose

[ 0, 1 ]

2

[ 0, 0 ]

intervention 1: Reformulated OXY 80-mg tablet x 1 dose taken without food. intervention 2: Original OxyContin® (OXY) 80-mg tablet x 1 dose taken without food.

intervention 1: Reformulated OXY (oxycodone HCl) intervention 2: Original OxyContin® (OXY) (oxycodone HCl)

1

Honolulu | Hawaii | United States | -157.85833 | 21.30694

0

NCT01101191

[ 4 ]

354

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

false

The purpose of the extension phase is to evaluate the long-term safety and tolerability of buprenorphine transdermal system (BTDS). Subjects begin the extension phase on BTDS 5 mcg/h and may up- or down-titrate the dose \[up to BTDS 20 micrograms (mcg) / hour (h)\] depending on adequate pain relief and tolerability.

Buprenorphine is a synthetic opioid analgesic with over 25 years of international clinical experience indicating it to be safe and effective in a variety of therapeutic situations for the relief of moderate to severe pain.

Back Pain Lower Back Chronic

Low back pain Opioid Transdermal

null

1

arm 1: Buprenorphine transdermal patch

[ 0 ]

3

[ 0, 0, 0 ]

intervention 1: Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear. intervention 2: Buprenorphine transdermal patch 10 mcg/h applied for 7-day wear. intervention 3: Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear.

intervention 1: Buprenorphine transdermal patch intervention 2: Buprenorphine transdermal patch intervention 3: Buprenorphine transdermal patch

84

0

NCT01125917

[ 2 ]

172

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

true

1FEMALE

false

The purpose of this study is to examine and compare the uptake of levomefolate calcium (Metafolin, a registered vitamin supplement) and folic acid in the body during 24 weeks of treatment with a following folate elimination phase of 20 weeks in healthy volunteers seeking contraception. Yasmin (oral contraceptive containing drospirenone and ethinylestradiol) was co-administered over the entire period of 44 weeks.

null

Contraception

null

2

arm 1: Combination EE/DRSP/ Metafolin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin\] given orally in a cyclic regimen for 24 weeks (6 cycles) in combination with folic acid placebo tablets (encapsulated). Each treatment cycle consisting of once daily hormone and Metafolin treatment for 21-days followed by once daily hormone free, Metafolin only regimen for 7 days. This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone. arm 2: Yasmin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)\] in combination with folic acid tablets 0.4 mg (encapsulated), given orally in a cyclic regimen for 24 weeks (6 cycles). Each treatment cycle providing once daily hormone and folic acid treatment for 21 days followed by once daily hormone free, folic acid only regimen for 7 days (encapsulated). This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.

[ 0, 0 ]

2

[ 0, 0 ]

intervention 1: Combination EE/DRSP/ Metafolin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin\] given orally in a cyclic regimen for 24 weeks (6 cycles) in combination with folic acid placebo tablets (encapsulated). Each treatment cycle consisting of once daily hormone and Metafolin treatment for 21-days followed by once daily hormone free, Metafolin only regimen for 7 days. This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone. intervention 2: Yasmin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)\] in combination with folic acid tablets 0.4 mg (encapsulated), given orally in a cyclic regimen for 24 weeks (6 cycles). Each treatment cycle providing once daily hormone and folic acid treatment for 21 days followed by once daily hormone free, folic acid only regimen for 7 days (encapsulated). This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.

intervention 1: EE 0.03 mg/DRSP 3 mg/Metafolin + folic acid placebo intervention 2: EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid

1

Neu-Ulm | Bavaria | Germany | 10.01112 | 48.39279

0

NCT01258660

[ 3 ]

217

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

false

The objective of the study was to generate the data necessary to determine the gabapentin exposure produced by 4 dose levels of GEn (600 mg, 1200 mg, 1800 mg, and 2400 mg) or placebo, and the corresponding relief of symptoms in subjects with Restless Legs Syndrome (RLS).

This was a multicenter, randomized, double blind, placebo controlled, parallel group study, comparing 4 doses of GEn (XP13512) with placebo given once daily to subjects with RLS. Eligible subjects were randomized in equal numbers into 1 of 5 treatment groups (GEn 600 mg, 1200 mg, 1800 mg, or 2400 mg or placebo) for 12 weeks of treatment. Data from this study will be utilized as part of a larger pharmacokinetic (PK) pharmacodynamic (PD) analysis of data from several studies (XP084/RXP111495) that are part of the GEn RLS clinical development program. Safety and tolerability were also assessed.

Restless Legs Syndrome

null

5

arm 1: GEn (XP13512/GSK1838262) 600 mg arm 2: GEn (XP13512/GSK1838262) 1200 mg arm 3: GEn (XP13512/GSK1838262) 1800 mg arm 4: GEn (XP13512/GSK1838262) 2400 mg arm 5: Placebo

[ 0, 0, 0, 0, 2 ]

2

[ 0, 0 ]

intervention 1: Double-Blind Treatment Phase: 600 mg GEn (XP13512) orally, once daily for 3 days followed by 600 or 1200 mg on days 4-6, followed by 600 or 1200 or 1800 mg on days 7-9, followed by 600 or 1200 or 1800 or 2400 mg on days 10-84. Double-Blind Taper Phase: 600 or 1200 or 1800 mg GEn (XP13512) orally, once daily on days 85-86, followed by 600 mg or 1200 mg on days 87-88, followed by 600 mg on days 89-91 intervention 2: Placebo orally once daily

intervention 1: GEn (XP13512/GSK1838262) intervention 2: Placebo

1

Dallas | Texas | United States | -96.80667 | 32.78306

0

NCT01332305

[ 3 ]

26

RANDOMIZED

CROSSOVER

0TREATMENT

4QUADRUPLE

false

0ALL

true

This randomized, placebo-controlled, double-blind 4x4 crossover clinical trial was part of a larger NIH-funded study to evaluate the analgesic efficacy of three doses of chronic oral (PO) dextromethorphan compared to placebo in central neuropathic pain following spinal cord injury. Subjects' maximally tolerated doses (MTD) were first determined to establish individual dose-analgesic response relationships in a run-in period; following a washout period, subjects were then randomized to receive an order of four doses of dextromethorphan (including placebo) in a 4x4 Latin square cross-over design.

null

Central Neuropathic Pain Allodynia Spinal Cord Injury

chronic pain central neuropathic pain spinal cord injury dextromethorphan lidocaine combination therapy analgesia

null

4

arm 1: 0% MTD Dextromethorphan arm 2: 25% MTD Dextromethorphan arm 3: 50% MTD Dextromethorphan arm 4: 100% MTD Dextromethorphan

[ 2, 0, 0, 0 ]

1

[ 0 ]

intervention 1: 0, 25, 50 and 100% of maximum tolerated dose, each administered over a 4 week period

intervention 1: Dextromethorphan

1

Boston | Massachusetts | United States | -71.05977 | 42.35843

0

NCT01435798

[ 2 ]

9

NA

SINGLE_GROUP

2DIAGNOSTIC

0NONE

true

0ALL

false

This study will determine how florbetapir F 18 (18F-AV-45) radioactivity is distributed throughout the body.

null

Alzheimer Disease

Amyloid imaging Positron Emission Tomography 18F-AV-45 florbetapir F 18 Diagnostic imaging

null

1

arm 1: Healthy male or female subjects, between 18 and 85 years of age.

[ 0 ]

1

[ 0 ]

intervention 1: IV injection, 370MBq (10mCi), single dose

intervention 1: florbetapir F 18

1

Jenkintown | Pennsylvania | United States | -75.12517 | 40.09594

0

NCT01564706

[ 1 ]

32

NON_RANDOMIZED

PARALLEL

2DIAGNOSTIC

0NONE

true

0ALL

false

A preliminary study to test how florbetapir F 18 (18F-AV-45) acts in the brains and bodies of healthy elderly people and patients with Alzheimer's Disease (AD) by using a positron emission tomography (PET) scanner.

null

Alzheimer Disease

Amyloid imaging Positron Emission Tomography 18F-AV-45 florbetapir F 18 Diagnostic imaging

null

2

arm 1: Probable AD, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, with mild/moderate dementia (Mini-Mental State Examination (MMSE) from 10 to 24) arm 2: Cognitively normal with MMSE of 29 or higher; age 50 years or older

[ 0, 0 ]

1

[ 0 ]

intervention 1: IV injection, 370MBq (10mCi), single dose

intervention 1: florbetapir F 18

3

0

NCT01565291

[ 3 ]

225

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

1FEMALE

null

This study will assess the efficacy and safety of intravenous (IV) trastuzumab (Herceptin) and IV docetaxel (Taxotere), with or without oral capecitabine (Xeloda), in women with previously untreated HER2-positive advanced and/or metastatic breast cancer.

null

Breast Cancer

null

2

arm 1: Participants will receive dual therapy with Herceptin and Taxotere until disease progression, unmanageable toxicity, or withdrawal. arm 2: Participants will receive triple therapy with Herceptin, Taxotere, and Xeloda until disease progression, unmanageable toxicity, or withdrawal.

[ 0, 0 ]

3

[ 0, 0, 0 ]

intervention 1: Participants will receive oral Xeloda, 950 mg/m\^2 twice a day on Days 1 to 14 of each 21-day cycle. intervention 2: Participants will receive Taxotere, 75 milligrams per meter-squared (mg/m\^2) in the Herceptin + Taxotere + Xeloda arm or 100 mg/m\^2 in the Herceptin + Taxotere arm, via IV infusion on Day 1 of each 21-day cycle. The lower starting dose will be used in the triple-therapy arm. intervention 3: Participants will receive Herceptin, 6 milligrams per kilogram (mg/kg) via IV infusion, on Day 1 of each 21-day cycle. The first dose will be a loading dose of 8 mg/kg in Cycle 1; the dose of 6 mg/kg will be given from Cycle 2 onward.

intervention 1: Xeloda intervention 2: Taxotere intervention 3: Herceptin

51

Adelaide | N/A | Australia | 138.59863 | -34.92866 Brisbane | N/A | Australia | 153.02809 | -27.46794 Camperdown | N/A | Australia | 151.17642 | -33.88965 Geelong | N/A | Australia | 144.36069 | -38.14711 Melbourne | N/A | Australia | 144.96332 | -37.814 Melbourne | N/A | Australia | 144.96332 | -37.814 Perth | N/A | Australia | 115.8614 | -31.95224 Southport | N/A | Australia | 153.39796 | -27.96724 Porto Alegre | N/A | Brazil | -51.23019 | -30.03283 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 Ottawa | Ontario | Canada | -75.69812 | 45.41117 Québec | Quebec | Canada | -71.21454 | 46.81228 San José | N/A | Costa Rica | -84.08489 | 9.93388 Turku | N/A | Finland | 22.26869 | 60.45148 Besançon | N/A | France | 6.01815 | 47.24878 Grenoble | N/A | France | 5.71479 | 45.17869 Marseille | N/A | France | 5.38107 | 43.29695 Paris | N/A | France | 2.3488 | 48.85341 Pierre-Bénite | N/A | France | 4.82424 | 45.70359 Rennes | N/A | France | -1.67429 | 48.11198 Athens | N/A | Greece | 23.72784 | 37.98376 Heraklion | N/A | Greece | 25.14341 | 35.32787 Pátrai | N/A | Greece | 21.73444 | 38.24444 Guatemala City | N/A | Guatemala | -90.51327 | 14.64072 Legnago | N/A | Italy | 11.30227 | 45.19365 Noale | N/A | Italy | 12.06445 | 45.54596 Rozzano | N/A | Italy | 9.1559 | 45.38193 Trento | N/A | Italy | 11.12108 | 46.06787 Treviglio | N/A | Italy | 9.59102 | 45.52081 Distrito Federal | N/A | Mexico | -93.02694 | 16.59 Mérida | N/A | Mexico | -89.62318 | 20.967 Monterrey | N/A | Mexico | -100.31721 | 25.68435 Monterrey | N/A | Mexico | -100.31721 | 25.68435 Panama City | N/A | Panama | -79.51973 | 8.9936 Gdansk | N/A | Poland | 18.64912 | 54.35227 Szczecin | N/A | Poland | 14.55302 | 53.42894 Barcelona | N/A | Spain | 2.15899 | 41.38879 Lleida | N/A | Spain | 0.62218 | 41.61674 Sabadell, Barcelona | N/A | Spain | N/A | N/A Zaragoza | N/A | Spain | -0.87734 | 41.65606 Karlstad | N/A | Sweden | 13.50357 | 59.3793 Västerås | N/A | Sweden | 16.55276 | 59.61617 Ipswich | N/A | United Kingdom | 1.15545 | 52.05917 Leeds | N/A | United Kingdom | -1.54785 | 53.79648 Manchester | N/A | United Kingdom | -2.23743 | 53.48095 Northwood | N/A | United Kingdom | -0.42454 | 51.61162 Oxford | N/A | United Kingdom | -1.25596 | 51.75222 Southampton | N/A | United Kingdom | -1.40428 | 50.90395 Weston-super-Mare | N/A | United Kingdom | -2.97665 | 51.34603

0

NCT02748213

[ 5 ]

135

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

true

The antidepressant medications are among the most commonly prescribed pharmacological agents in patients with mood and anxiety disorder. Despite recent advances in antidepressant pharmacotherapy, there is a pressing need for substantial optimization and improvment of outcome of pharmacotherapy of psychiatric disorders by providing individualized and science-based treatment guidelines. Besides it is rather difficult in clinical practice to predict, which patient will response to a certain pharmacological treatment well and which one less so. Putative predictors of response to antidepressant include demographic and clinical characteristics, personality traits, biological markers and psychophysiological features. Recently the research studies shown that divergences in antidepressant efficacy may be related to genetic variations of patients. The pharmacogenetic studies have multiplied in recent decade due to the impact that such studies may have in everyday clinical practice once reliable predictors could be identified. The pharmacogenetic research using new DNA microarray-based technology can reasonably be expected to contribute to the prediction of likelihood of treatment response and risk of development of adverse side effects in individual patients in case of antidepressant treatment. By reducing costly treatment failures and the likelihood of serious adverse events, pharmacogenetic testing may help to improve the treatment possibilities for chronic diseases, reduce the burden prescription drug costs, and lower the costs of drug development. The further detailed investigation of peripheral gene expression profiles may help to identify responsible genes that underlie the process of development of affective disorders and open novel horizons for understanding molecular mechanisms of psychopharmacological treatment.

To participate in the study the subjects must be at least 18 years old and give a written informed consent after an oral and written explanation of the study aims and methods. The study sample will include the female and male patients with panic disorder or major depression diagnosis according to DSM-IV criteria. Patients will be recruited from the out- and inpatients services of the Psychiatric Clinic of the Tartu University Hospital. For the detailed assessment of clinical severity of specific disorder and treatment effects the disorder-specific rating scales: Montgomery-Asberg's Depression Rating Scale (MADRS), Clinical Global Impression scale (CGI) will be used. The adverse effects will be evaluated by letting the patients to fill the checklist of side-symptoms. In both patient groups (with panic disorder and major depression) an SSRI escitalopram (Cipralex) will be administrated for 12 weeks in flexible dose ranging between 10 - 20 mg/per day. At the end of week 12 the patients will defined as responders if the decrease in MADRS scores is at least 50% and score on the CGI improvement scale is 2 or less. The remitters will defined if the scores are less than 12 on the MADRS. Patients who do not meet these criteria will defined as non-responders and non-remitters respectively. Depressive patients, showing non-response to escitalopram monotherapy will given the combination of 20 mg of escitalopram and 150-300 mg of bupropion (Wellbutrin SR) for 6 weeks.

Major Depression

Treatment efficacy Safety

null

1

arm 1: No comparator

[ 0 ]

2

[ 0, 0 ]

intervention 1: escitalopram 10-20mg per day 12 weeks intervention 2: bupropion 150-300mg per day 6 weeks

intervention 1: escitalopram intervention 2: bupropion

1

Tartu | N/A | Estonia | 26.72509 | 58.38062

0

NCT03927950

[ 5 ]

318

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

null

Assess the efficacy \& tolerability of Vyvanse when children aged 6-12 years diagnosed with ADHD are dosed to optimal effect.

Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (lisdexamfetamine dimesylate) in Children aged 6-12 Diagnosed with ADHD

Attention Deficit Hyperactivity Disorder (ADHD)

null

1

arm 1: None

[ 0 ]

1

[ 0 ]

intervention 1: Vyvanse™ 20mg once daily at 7 a.m.; dose increased weekly by 10mg until an acceptable response is achieved. Titration may proceed to a maximum daily dose 70mg/day.

intervention 1: Vyvanse (lisdexamfetamine dimesylate)

46

0

NCT00500071

[ 4 ]

217

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

null

To assess efficacy and safety of SPD503(guanfacine hydrochloride) in subjects with ADHD and oppositional symptoms.

null

ADHD

null

2

arm 1: None arm 2: None

[ 0, 2 ]

2

[ 0, 0 ]

intervention 1: Subjects will start at 1mg tablet each morning and will subsequently be titrated (in 1 mg weekly increments) to optimal dose based upon tolerance and response to investigational product (not to exceed 4 mg/day). intervention 2: Placebo

intervention 1: SPD503 (Guanfacine hydrochloride) intervention 2: Placebo

34

0

NCT00367835

[ 3 ]

234

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

0ALL

false

A Phase II trial to demonstrate the safety and efficacy of PTK 0796 in the treatment of complicated skin and skin structure infections (cSSSI).

The pharmacologic profile of PTK 0796 in humans suggests that it has the potential to be used safely and effectively for this indication. Data from in vitro and animal studies support this hypothesis. In PTK 0796-CSSI-0702 the safety and efficacy of PTK 0796 in the treatment of cSSSI will be compared to an antibiotic approved for this indication by FDA. Initial treatment will be administered intravenously with the option for subsequent oral treatment.

Infectious Skin Disease Bacterial Skin Disease

CSSSI

null

2

arm 1: None arm 2: None

[ 0, 1 ]

2

[ 0, 0 ]

intervention 1: PTK 0796 100 mg for injection; PTK 0796 capsule 100 mg intervention 2: Pre-mixed 600 mg IV infusion solution; Linezolid 600 mg tablets

intervention 1: PTK 0796 intervention 2: Linezolid

11

0

NCT03716024

[ 5 ]

58

NON_RANDOMIZED

SINGLE_GROUP

0TREATMENT

0NONE

false

1FEMALE

false

The aim of this study is to evaluate efficacy and tolerability, and number of positive response to treatment with CAELYX (50 mg/m\^2), administered as monotherapy once per 4 weeks to patients with metastatic epithelial ovarian cancer, resistant to previous platinum therapy.

null

Ovarian Neoplasms

null

1

arm 1: Caelyx Intravenous, 50 mg/m\^2, given for 6 cycles

[ 0 ]

1

[ 0 ]

intervention 1: Caelyx Intravenous, 50 mg/m\^2 (60 minute infusion) on day 1, every 4 weeks, during 6 cycles

intervention 1: Pegylated Liposomal Doxorubicin hydrochloride

0

null

0

NCT00727961

[ 3 ]

20

NON_RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

false

Background: The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months. Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens. Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. Even with a reduction in treatment related mortality, success with allogeneic SCT is limited by a significant risk of relapse. Donor immunization with myeloma Id in the setting of a non-myeloablative allogeneic SCT may represent a novel strategy for the treatment of multiple myeloma. Objectives: Primary Objectives: To induce cellular and humoral immunity in allogeneic stem cell donors and recipients against the unique idiotype expressed by the recipient's myeloma. To determine whether antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic SCT recipient in the setting of a non-myeloablative conditioning regimen. Secondary Objectives: To evaluate the effect of the Fludarabine-(etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide) EPOCH regimen on host T cell depletion and myeloid depletion prior to allogeneic SCT. To determine the efficacy of a novel conventional chemotherapy regimen (Fludarabine-EPOCH) in the setting multiple myeloma. To determine the treatment-related morbidity and mortality of allogeneic stem cell transplantation using a non-myeloablative conditioning regimen in multiple myeloma. To determine if the re-vaccination of allogeneic stem cell donors with the unique idiotype expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient specific-idiotype prior to lymphocyte donation for the treatment of patients with recurrent or progressive disease after transplantation. Eligibility: Patients 18-75 years of age with Immunoglobulin G (IgG) or Immunoglobulin A (IgA) multiple myeloma. Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation. Consenting first degree relative matched at 6/6 or 5/6 human leukocyte antigen (HLA) antigens. Design: Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related toxicity. Recipient will undergo a plasmapheresis to obtain starting material for the isolation of idiotype protein. Donors would be immunized with an Id vaccine prepared from the patient. Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim. Recipients will be immunized with the Id vaccine following transplantation.

Background: The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic chemotherapy. Although partial remissions of up to 60% are obtained with conventional regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months. Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens. Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in allo-engraftment. Even with a reduction in treatment related mortality, success with allogeneic SCT is limited by a significant risk of relapse. Donor immunization with myeloma Id in the setting of a non-myeloablative allogeneic SCT may represent a novel strategy for the treatment of multiple myeloma. Objectives: Primary Objectives: To induce cellular and humoral immunity in allogeneic stem cell donors and recipients against the unique idiotype expressed by the recipient's myeloma. To determine whether antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic SCT recipient in the setting of a non-myeloablative conditioning regimen. Secondary Objectives: To evaluate the effect of the Fludarabine-EPOCH regimen on host T cell depletion and myeloid depletion prior to allogeneic SCT. To determine the efficacy of a novel conventional chemotherapy regimen (Fludarabine-EPOCH) in the setting multiple myeloma. To determine the treatment-related morbidity and mortality of allogeneic stem cell transplantation using a non-myeloablative conditioning regimen in multiple myeloma. To determine if the re-vaccination of allogeneic stem cell donors with the unique idiotype expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient specific-idiotype prior to lymphocyte donation for the treatment of patients with recurrent or progressive disease after transplantation. Eligibility: Patients 18-75 years of age with IgG or IgA multiple myeloma. Patients must have achieved at least a partial remission following initial conventional chemotherapy regimen or after autologous stem cell transplantation. Consenting first degree relative matched at 6/6 or 5/6 HLA antigens. Design: Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related toxicity. Recipient will undergo a plasmapheresis to obtain starting material for the isolation of idiotype protein. Donors would be immunized with an Id vaccine prepared from the patient. Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim. Recipients will be immunized with the Id vaccine following transplantation.

Multiple Myeloma

Immunoablative Mobilization Apheresis Multiple Myeloma IgG Multiple Myeloma IgA Multiple Myeloma

null

2

arm 1: Induction chemotherapy with fludarabine, etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and granulocyte colony stimulating factor (GCSF) followed by transplant preparative regimen chemotherapy with fludarabine, cyclophosphamide, mesna, cyclosporine, and methotrexate, followed by stem cell infusion and immunization. arm 2: 3 subcutaneous injections of myeloma protein within 10 weeks before stem cell collection. The first (week 0) second (week 2), and third injection (week 6) with Id-KLH (Anti-idiotype-keyhole limpet hemocyanin) (0.5 mg subcutaneous day 1) and Granulocyte macrophage-colony stimulating factor (GM-CSF) (250 mcg/m\^2 subcutaneous on days 1-4). Stem cell collection is 4 weeks after the third vaccination.

[ 0, 5 ]

12

[ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 2, 2 ]

intervention 1: 3 subcutaneous (SC) injections of myeloma protein within 10 weeks before stem cell collection the first (week 0), second (week 2), and third injection (week 6) with Id-KLH (0.5 mg SC day 1) intervention 2: Induction chemotherapy: 1.3 mg/m\^2 bolus intravenous injection twice weekly for 2 weeks (days 1, 4, 8, 11) followed by 10 day rest period (day 12-21) intervention 3: Induction chemotherapy: 600 mg/m\^2 day 4 Transplant: 1200 mg/m\^2 intravenous x 4 days (days -6, -5, -4, -3) intervention 4: Transplant: 2 mg/kg intravenous every 12 hours continuous intravenous or by mouth (PO) until day + 180 intervention 5: Induction chemotherapy: 10 mg/m\^2 day continuous intravenous (CIV) days 1-3 intervention 6: Induction chemotherapy: 50 mg/m\^2 day continuous intravenous days 1-3 intervention 7: Induction chemotherapy: 25 mg/m\^2 day intravenous days 1-3 Transplant: 30 mg/m\^2 day x 4 days (days -6, -5, -4, -3 ) intervention 8: 60 mg/m\^2 day 1-4 intervention 9: Induction chemotherapy: 0.5 mg/m\^2 day continuous intravenous days 1-3 intervention 10: Transplant: 5 mg/m\^2 intravenous on days +1, +3, +6, +11 intervention 11: 250 mcg/m\^2 subcutaneously every day, days 1-4 intervention 12: 10 mcg/kg per day subcutaneously daily from day 5 until absolute neutrophil count (ANC) \> 1000/ul x 2 days

intervention 1: Myeloma Immunoglobulin Idiotype Vaccine intervention 2: Bortezomib intervention 3: Cyclophosphamide intervention 4: Cyclosporine intervention 5: Doxorubicin hydrochloride intervention 6: Etoposide intervention 7: Fludarabine phosphate intervention 8: Prednisone intervention 9: Vincristine Sulfate intervention 10: Methotrexate intervention 11: GMCSF (granulocyte macrophage colony stimulating factor) intervention 12: GCSF (granulocyte colony stimulating factor)

1

Bethesda | Maryland | United States | -77.10026 | 38.98067

0

NCT00006184

[ 4 ]

1,509

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

1FEMALE

true

To investigate the efficacy and safety of a single injection of 150 μg Corifollitropin Alfa (Organon 36286) to induce multifollicular development for controlled ovarian stimulation using daily recombinant FSH (recFSH) as a reference. The primary hypothesis is that a single injection of Corifollitropin Alfa is non-inferior to daily treatment with recFSH in initiating multifollicular growth.

This is a randomized, double-blind, active-controlled, non-inferiority clinical trial investigating the efficacy and safety of a new treatment regimen with Corifollitropin Alfa, a recombinant gonadotropin applied to initiate and sustain follicular stimulation in controlled ovarian stimulation for Assisted Reproductive Technology (ART). For this regimen, participants receive a single injection of Corifollitropin Alfa and one week later, treatment is continued with daily recFSH up to the day of triggering final oocyte maturation. In the reference group participants receive daily injections of recFSH up to the day of triggering final oocyte maturation. Non-inferiority in ongoing pregnancy rates (assessed at least 10 weeks after embryo transfer) will be the primary endpoint for this trial. The number of oocytes retrieved will be analyzed as co-primary endpoint.

In Vitro Fertilization

Infertility Pharmacological effect of drugs Hormones Hormone substitutes and hormone antagonists Pharmacological actions Randomized Multi-center Multi-national Double-blind Active-controlled Non-inferiority

null

2

arm 1: Participants received a single subcutaneous (SC) injection of 150 µg Corifollitropin Alfa (org 36286) on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections from Stimulation Days 1 to 7 with placebo-recFSH; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were administered from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was given when 3 follicles \>= 17 mm. On the day of oocyte pick up (OPU) daily doses of progesterone were started and continued for up to 6 weeks or menses. arm 2: Participants received a single SC injection of placebo Corifollitropin Alfa on day 2 or 3 of the menstrual cycle (Stimulation Day 1); 7 daily SC injections with 200 IU recFSH from Stimulation Days 1 to 7; followed by daily SC injections with 200 IU recFSH up to the day of hCG. Daily SC injections of Ganirelix were given from Stimulation Day 5 to the day of hCG; at which time a single dose of hCG was administered when 3 follicles \>= 17 mm. On the day of OPU daily doses of progesterone were started and continued for up to 6 weeks or menses.

[ 0, 1 ]

8

[ 0, 2, 0, 0, 2, 0, 2, 2 ]

intervention 1: On the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection of 150 μg (0.5 mL) Corifollitropin Alfa was administered in the abdominal wall. intervention 2: Daily SC injections with 200 IU fixed dose recFSH were started on Stimulation Day 1 and continued up to and including Stimulation Day 7. intervention 3: Pre-filled syringe containing an identical solution when compared to Corifollitropin Alfa. On the morning of day 2 or 3 of the menstrual cycle (Stimulation Day 1), a single SC injection was administered in the abdominal wall. intervention 4: Identical ready-for-use solution, but without the active ingedient, supplied in cartridges for SC injection with the Follistim Pen. Daily SC injections were started on Stimulation Day 1 and continued up to and including Stimulation Day 7. intervention 5: From Stimulation Day 8 onwards a daily SC dose of 200 IU recFSH was administered up to and including the Day of hCG. intervention 6: On Stimulation Day 5 a daily SC injection of 0.25 mg was started, which continued up to and including the day of hCG intervention 7: When 3 follicles \>= 17 mm were observed by USS, a single dose of 10,000 IU/USP hCG was administered; or, for those at risk for Ovarian Hyperstimulation Syndrome (OHSS), a lower dose of 5,000 IU/USP intervention 8: On the day of OPU, luteal phase support was started by administering micronized progesterone of at least 600 mg/day vaginally, or at least 50 mg/day intramuscular (IM), which continued for at least 6 weeks, or up to menses.

intervention 1: Corifollitropin alfa intervention 2: RecFSH / Follitropin beta (Days 1 to 7) intervention 3: Placebo Corifollitropin alfa intervention 4: Placebo RecFSH / follitropin beta intervention 5: RecFSH / Follitropin beta (Days 8 to hCG) intervention 6: Ganirelix intervention 7: hCG intervention 8: Progesterone

0

null

0

NCT00696800

[ 3 ]

35

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

false

This is a phase II, randomized, multicenter, open-label study designed to assess the safety and tolerability of concomitant chemotherapy with low-dose temozolomide during whole brain radiation and later on at 14 days on/14 days off schedule in patients with cerebral metastases from non-small cell lung cancer (NSCLC). The response to temozolomide will be evaluated by clinical follow up and Magnetic Resonance Imaging (MRI) performed every 2 months. Progression-free survival at 6 months, duration of overall survival, and quality of life will also be evaluated.

null

Carcinoma, Non-Small-Cell Lung

temozolomide radiotherapy

null

2

arm 1: None arm 2: None

[ 0, 1 ]

2

[ 0, 3 ]

intervention 1: Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100 mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2). intervention 2: 2 regimens are allowed: a) 20 fractions of 2 Gray each, administered on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.

intervention 1: Temozolomide and radiotherapy intervention 2: Whole brain radiotherapy

0

null

0

NCT00266812

[ 2 ]

25

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

false

To monitor for endocrine changes in response to treatment of cataplexy with Xyrem, to focus on the hypothalamic pituitary axis and to confirm the safety of Xyrem on potential endocrine changes.

null

Narcolepsy With Cataplexy

Endocrine Evaluation cataplexy sodium oxybate (xyrem)

null

1

arm 1: * Active Substance: Sodium Oxybate * Pharmaceutical form: Oral Solution * Concentration: 500 mg/mL oral solution from 4.5 to 9 g/day divided into two equal doses during 12 weeks * Route of administration: Oral

[ 0 ]

1

[ 0 ]

intervention 1: * Active Substance: Sodium Oxybate * Pharmaceutical form: Oral Solution * Concentration: 500 mg/mL oral solution from 4.5 to 9 g/day divided into two equal doses during 12 weeks * Route of administration: Oral

intervention 1: Sodium Oxybate (Xyrem)

1

Liège | N/A | Belgium | 5.56749 | 50.63373

0

NCT00345800

[ 3 ]

24

NON_RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

null

Age related differences in response to a drug could arise from variation in pharmacokinetic (PK) and/or pharmacodynamic (PD) profiles between age groups. Whilst the efficacy and safety profile of anagrelide is well established through a well-documented clinical trial programme in patients of all ages, no formal studies have been carried out to investigate whether the PK profile of anagrelide and its metabolites is altered with age. This study is designed to allow comparisons to be made in terms of pharmacokinetics of anagrelide and its metabolites between elderly (≥ 65 years) and young (18-50 years) ET patients

null

Essential Thrombocythaemia

null

2

arm 1: None arm 2: None

[ 0, 0 ]

2

[ 0, 0 ]

intervention 1: Anagrelide hydrochloride 0.5 mg per capsule; participants will be stable on an anagrelide treatment regimen and will take capsules from their own prescription except on the PK day when the participant specific anagrelide dose will be administered from a controlled study specific supply. intervention 2: Anagrelide hydrochloride 0.5 mg per capsule; participants will be stable on an anagrelide regimen and will take capsules from their own prescription except on the PK day when the participant specific anagrelide dose will be administered from a controlled study specific supply.

intervention 1: anagrelide hydrochloride intervention 2: anagrelide hydrochloride

5

Barcelona | N/A | Spain | 2.15899 | 41.38879 Luleå | N/A | Sweden | 22.15465 | 65.58415 Uppsala | N/A | Sweden | 17.63889 | 59.85882 Uppsala | N/A | Sweden | 17.63889 | 59.85882 Belfast | N/A | United Kingdom | -5.92541 | 54.59682

0

NCT00413634

[ 3 ]

252

RANDOMIZED

PARALLEL

4SUPPORTIVE_CARE

2DOUBLE

false

0ALL

null

The purpose of this research study is to evaluate the safety and effectiveness of pegfilgrastim in reducing grade 3/4 neutropenia when given after one of three chemotherapy regimens (FOIL, FOLFOX or FOLFIRI) in patients with locally advanced or metastatic colorectal cancer. This study is considered to be "investigational" because the time between receiving pegfilgrastim and the next cycle of chemotherapy is only 11 days.

null

Colon Cancer Colorectal Cancer Rectal Cancer

Neulasta® pegfilgrastim Advanced Chemotherapy

null

2

arm 1: 6 mg pegfilgrastim arm 2: 6 mg placebo

[ 1, 2 ]

2

[ 0, 0 ]

intervention 1: Subjects randomized to placebo will receive a 6 mg subcutaneous injection once per cycle at least 24 hours after completion of 5-FU chemotherapy infusion. Subjects will continue to receive one injection per cycle until completion of 4 cycles, or until early termination from the study treatment period, whichever occurs first. intervention 2: Subjects randomized to pegfilgrastim will receive a 6 mg subcutaneous injection once per cycle at least 24 hours after completion of 5-FU chemotherapy infusion. Subjects will continue to receive one injection per cycle until completion of 4 cycles, or until early termination from the study treatment period, whichever occurs first.

intervention 1: Placebo intervention 2: Pegfilgrastim

0

null

0

NCT00094809

[ 3 ]

135

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

0ALL

false

The purpose of this study is to evaluate the safety and blood pressure lowering effect of different doses of PF-00489791 in patients with mild to moderate high blood pressure

null

Hypertension

Clinical Trial Randomized Controlled Trial Humans Cyclic Nucleotide Phosphodiesterases Type 5

null

4

arm 1: None arm 2: None arm 3: None arm 4: None

[ 2, 0, 0, 0 ]

4

[ 0, 0, 0, 0 ]

intervention 1: placebo, oral, tablets, once daily, for 28 days intervention 2: PF-00489791 20 mg titrated to 40 mg, oral, tablets, once daily, for 28 days intervention 3: PF-00489791 4 mg, oral, tablets, once daily, for 28 days intervention 4: PF-00489791 10 mg, oral, tablets, once daily, for 28 days

intervention 1: placebo intervention 2: PF-00489791 intervention 3: PF-00489791 intervention 4: PF-00489791

20

0

NCT00422461

[ 3 ]

9

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

2MALE

true

Study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.

This was a Phase 2, open-label study in male participants with Fabry disease. All participants who met initial eligibility criteria underwent a 28-day screening period, including a 14-day run-in with migalastat (150 milligrams \[mg\] migalastat once a day \[QD\] from Days -28 to -15) to assess eligibility for entering the treatment period of the study. Participants who entered the treatment period were required to have α-galactosidase A (α-Gal A) activity responsive to migalastat. Fifteen participants received at least 1 dose of study drug, however, 6 of these participants did not demonstrate α-Gal A activity responsive to migalastat and were thus screen failures (these participants are hereafter referred to as "dosed screen failures") due to not meeting all inclusion criteria for treatment. Therefore, 9 participants were enrolled into the treatment period (these participants are hereafter referred to as "eligible-enrolled"). Eligible-enrolled participants (those who satisfied the criteria for inclusion in the study) received escalating doses of migalastat twice a day (BID) for 6 weeks (Days 1 to 42), followed by 6 weeks at 1 dose level BID (Days 43 to 84) during the treatment period. Participants could then opt to participate in the extension period. The study consisted of 2 optional extension periods, the first through Week 48 and the second through Week 96. For participants who did not continue into the optional treatment extension, the study included a 2-week follow-up period.

Fabry Disease

Amicus Therapeutics AT1001 Galafold Migalastat Substrate

null

1

arm 1: Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods. Treatment Period: * Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14). * Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28). * Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42). * Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84). Extension Period: * Migalastat 25 mg BID for Weeks 12 through 48. * Migalastat 50 mg QD for Weeks 48 through 96.

[ 0 ]

1

[ 0 ]

intervention 1: None

intervention 1: migalastat HCl

5

0

NCT00214500

[ 5 ]

15

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

true

0ALL

false

Randomized, double-blinded study that will evaluate the tolerability, safety, and flow rates of different solutions subcutaneously (SC) infused and preceded by human recombinant hyaluronidase (hylenex) 150 units. In Stage 1, the comparison will be Normal Saline (NS) solution to Lactated Ringer's (LR) solution. Each subject will receive 500 milliliters (mL) of solution, consisting of NS in one thigh and LR in the other thigh. Immediately prior to the infusions, each thigh will have 150 units of hylenex. In Stage 2, the comparison will be NS solution and buffered NS solution.

This Phase IV, randomized, double-blinded study in volunteer subjects to evaluate the tolerability, safety, and flow rates of different solutions subcutaneously (SC) infused and preceded by human recombinant hyaluronidase (hylenex) 150 units. The study will be conducted in two sequential stages. In Stage 1, the comparison will be NS solution to LR solution. Each subject will receive simultaneous SC infusions of 500 mL (from a 500 mL bag) of solution in each anterior thigh, consisting of NS in one thigh and LR in the other thigh. The thighs (left vs. right) to receive NS and LR will be randomized and double blinded. Immediately prior to the infusions, each thigh will have 150 units of hylenex simultaneously injected. Tolerability will be assessed based on the subject's self-assessment of discomfort on a visual analog scale (VAS). Safety will be assessed by physical examination targeted at infusion sites, vital signs, and adverse events. The amount of fluid infused will be assessed by weighing the infusion bag, fluid and tubing at designated time points, and allowing the determination of flow rate. Stage 2 will be conducted only if the observed Stage 1 VAS mean maximum pain score is at least 25 mm higher for one solution compared to the other. Stage 2 will evaluate the tolerability, safety, and flow rates of subcutaneously infused NS solution and buffered NS solution.

Healthy

Hylenex subcutaneous infusion hyaluronidase rHuPH20 recombinant human hyaluronidase

null

2

arm 1: Normal Saline (NS) and Hylenex arm 2: Lactated Ringer's (LR) and Hylenex

[ 0, 0 ]

1

[ 0 ]

intervention 1: 150 Units in 1mL

intervention 1: recombinant human hyaluronidase

1

Kalamazoo | Michigan | United States | -85.58723 | 42.29171

0

NCT00656370

[ 2, 3 ]

10

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

false

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. The purpose of this study is to evaluate the long term safety of enzyme replacement therapy with DRX008A (VPRIV®, GA-GCB; velaglucerase alfa) in patients with type 1 Gaucher disease.

Type 1 Gaucher disease, the most common form, accounts for more than 90% of all cases and does not involve the central nervous system (CNS). Typical manifestations of type 1 Gaucher disease include hepatomegaly, splenomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation, pulmonary disease, and decreased quality of life. Gene-Activated® human glucocerebrosidase (the long term safety of enzyme replacement therapy with DRX008A (GA-GCB; velaglucerase alfa) is produced in a continuous human cell line using proprietary gene-activation technology and has an identical amino acid sequence to the naturally occurring human enzyme. GA-GCB (velaglucerase alfa) contains terminal mannose residues that target the enzyme to the macrophages-the primary target cells in Gaucher disease. This study was designed to evaluate the long term safety of GA-GCB (velaglucerase alfa) in patients with Type 1 Gaucher disease

Gaucher Disease

Gaucher disease, Enzyme Replacement Therapy

null

1

arm 1: 15-60 U/kg every other week via intravenous infusion

[ 0 ]

1

[ 0 ]

intervention 1: 15-60 U/kg every other week via intravenous infusion

intervention 1: GA-GCB

3

Jerusalem | N/A | Israel | 35.21633 | 31.76904 Bucharest | N/A | Romania | 26.10626 | 44.43225 Belgrade | N/A | Serbia | 20.46513 | 44.80401

0

NCT00391625

[ 0 ]

70

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

true

0ALL

false

The purpose of this study is to find out whether atomoxetine (also called Strattera) helps teenagers (12-19) with Attention Deficit Hyperactivity Disorder (ADHD) and drug/alcohol problems.

Evidence-based psychosocial treatments have recently been developed. However, very little data exist on the use of pharmacotherapy for adolescents SUD (Substance Use Disorder). One promising pharmacotherapy approach is to treat co-occuring psychiatric disorders. A common co-occurring disorder in adolescent SUD is attention-deficit/hyperactivity disorder (ADHD). Fortunately, new ADHD medications, such as atomoxetine, that do not have addictive potential are now available. However, all controlled studies of atomoxetine have specifically excluded teens with SUD. Therefore, little data exist on the safety and efficacy of the medication in this population. This research project will address the important research gap with the specific aim: to conduct a randomized, placebo-controlled trial of atomoxetine for ADHD in teens with SUD.

Attention Deficit Hyperactivity Disorder Substance Abuse

Adolescent ADHD SUD

null

2

arm 1: placebo plus individual cognitive behavioral therapy arm 2: atomoxetine plus individual cognitive behavioral therapy

[ 2, 0 ]

2

[ 0, 0 ]

intervention 1: Half of participants are randomized to atomoxetine plus individual cognitive behavioral therapy targeting substance use disorder intervention 2: Half of participants are randomized to placebo plus individual cognitive behavioral therapy targeting substance use disorder

intervention 1: Atomoxetine intervention 2: Placebo

1

Denver | Colorado | United States | -104.9847 | 39.73915

1

NCT00399763

[ 4 ]

91

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

false

The objective of the trial is to determine the relationship within a participant between the time to manual detection of the reappearance of the fourth twitch (T4) measured using a peripheral nerve stimulator (PNS) and the time to recovery of the fourth twitch/first twitch (T4/T1) ratio to 0.9 measured using a Train Of Four (TOF)-Watch® SX, of 4.0 mg/kg sugammadex administered at 15 minutes after either a bolus dose of 0.6 mg/kg rocuronium or the last maintenance dose of 0.15 mg/kg rocuronium.

The TOF-Watch® SX has been used for neuromuscular monitoring in all clinical trials with sugammadex. In clinical practice however, a PNS is commonly used in many hospitals worldwide. A disadvantage of a PNS is that it is not objective monitoring like the TOF-Watch® SX, and it can detect only the number of twitches. In this trial, the relationship between the time to reappearance of T4 using PNS (i.e. Ministim® model MS-IV) and the time to recovery of the T4/T1 ratio to 0.9 using the TOF-Watch® SX was determined after a dose of 4.0 mg/kg sugammadex was administered 15 minutes after the last dose of rocuronium. Determining this relationship will enable the provision of advice on when it is safe to extubate participants after administration of 4.0 mg/kg sugammadex for reversing neuromuscular block while using a PNS. The time to reappearance of T4 was assessed by a blinded PNS-assessor. This assessor was blinded for the dose of sugammadex used and for the TOF results measured with the TOF-Watch® SX.

Neuromuscular Blockade

null

4

arm 1: sugammadex 1.0 mg/kg, TOF-Watch® SX (dominant forearm) and PNS (non-dominant forearm) arm 2: sugammadex 1.0 mg/kg, TOF-Watch® SX (non-dominant forearm) and PNS (dominant forearm) arm 3: sugammadex 4.0 mg/kg, TOF-Watch® SX (dominant forearm) and PNS (non-dominant forearm) arm 4: sugammadex 4.0 mg/kg, TOF-Watch® SX (non-dominant forearm) and PNS (dominant forearm)

[ 0, 0, 0, 0 ]

1

[ 0 ]

intervention 1: Participants will receive an intubating dose of 0.6 mg/kg rocuronium, followed by one or more maintenance doses of 0.15 mg/kg rocuronium, if necessary. Fifteen minutes after the last dose of rocuronium, 1.0 or 4.0 mg/kg sugammadex will be randomly administered by intravenous (IV) bolus dose based on actual body weight.

intervention 1: sugammadex

0

null

1

NCT00535496

[ 3 ]

122

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

true

The primary purpose of this study is to evaluate the safety and dose-response relationship of N-methylnaltrexone bromide (MOA-728) by observing spontaneous bowel movements in subjects with chronic pain, which is not due to malignant cancer, and who have opioid-induced bowel dysfunction (OIBD).

null

Constipation

null

5

arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None

[ 2, 0, 0, 0, 0 ]

2

[ 0, 10 ]

intervention 1: Oral intervention 2: placebo

intervention 1: N-methylnaltrexone bromide (MOA-728) intervention 2: placebo

41

1

NCT00547586

[ 4 ]

9,809

RANDOMIZED

PARALLEL

1PREVENTION

0NONE

false

0ALL

true

The purpose of the study is to determine whether there is an increased all-cause mortality in sertindole-treated patients in comparison to patients treated with a well-known antipsychotic (risperidone) when used under normal marketed conditions in the treatment of schizophrenia.

The Committee for Medicinal Products for Human Use (CHMP) requested a post-marketing study to ascertain that the favourable benefit-risk profile and low mortality rates seen in the clinical studies with sertindole would not be offset by higher mortality rates when sertindole was used under more normal conditions of use. It was recognised that, in a clinical trial setting, strict patient selection and monitoring could lead to higher compliance in patient management and thereby to a lower mortality rate. Study 99824 was therefore designed in collaboration with the CHMP as an open-label, randomised study with minimum study management that focused on mortality and general patient safety. The duration of the treatment period was not fixed. No efficacy measures were included.

Schizophrenia

null

2

arm 1: Normally in the range of 4 to 20 mg/day arm 2: Normally in the range of 2 to 8 mg/day

[ 0, 1 ]

2

[ 0, 0 ]

intervention 1: Sertindole was supplied as 4, 12, 16, and 20 mg tablets. The start and maintenance dosages as well as dose titration were set by the investigator, in accordance with the national Summary of Product Characteristics (SPC) for sertindole; in countries where sertindole was not marketed, the European Union (EU) SPC applied (all national and EU SPCs were essentially identical). Recommended dose range: 12 to 20 mg/day. The investigators were instructed to contact H. Lundbeck A/S if they deemed it necessary to increase the dose of sertindole to 24 mg/day, which was allowed in exceptional cases intervention 2: Risperidone was supplied as 1, 2, 3, and 4 mg tablets. The start and maintenance dosages as well as dose titration were set by the investigator, in accordance with the national SPC for risperidone. Recommended dose range: 2 to 8 mg/day

intervention 1: Sertindole intervention 2: Risperidone

0

null

1

NCT00856583

[ 3 ]

68

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

1FEMALE

false

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining paclitaxel, cisplatin, and liposomal doxorubicin in treating women who have undergone surgery for stage III ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

OBJECTIVES: * Determine the efficacy of intraperitoneal (IP) cisplatin, IP and IV paclitaxel, and IV doxorubicin HCl liposome, in terms of progression-free survival and overall survival, in patients with optimally debulked stage III ovarian epithelial, fallopian tube, or primary peritoneal cancer. * Determine the feasibility of and toxic effects associated with this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive paclitaxel IV over 3 hours on day 1, intraperitoneal (IP) cisplatin over 30-60 minutes on day 2, IP paclitaxel over 30-60 minutes on day 8, and doxorubicin HCl liposome IV over 1 hour on day 8. Patients not able to tolerate IP infusion receive paclitaxel IV and cisplatin IV on day 1 only. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for 2 years and then annually thereafter. PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study within 4 years.

Fallopian Tube Cancer Ovarian Cancer Peritoneal Cavity Cancer

stage III ovarian epithelial cancer peritoneal cavity cancer fallopian tube cancer

null

1

arm 1: paclitaxel, cisplatin and liposomal doxorubicin

[ 0 ]

3

[ 0, 0, 0 ]

intervention 1: None intervention 2: None intervention 3: None

intervention 1: cisplatin intervention 2: liposomal doxorubicin intervention 3: paclitaxel

104

0

NCT00003896

[ 3 ]

137

NON_RANDOMIZED

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

false

Evaluate anti-cancer activity (e.g. proportion of patients with confirmed complete response or partial response) in patients with advanced, inoperable biopsy-proven hepatocellular carcinoma.

In addition to the key secondary outcome parameters the following exploratory parameters were evaluated in subpopulations: * Pharmacokinetics (PK) profile of Sorafenib * Plasma and tissue tumor biomarkers

Carcinoma, Hepatocellular

Cancer Liver Cancer Hepatocellular carcinoma (HCC)

null

1

arm 1: Sorafenib (Nexavar, BAY43-9006) 400 mg administered bis in die (bid, twice a day)

[ 0 ]

1

[ 0 ]

intervention 1: Sorafenib (Nexavar, BAY43-9006) 400 mg administered bis in die (bid, twice a day)

intervention 1: Sorafenib (Nexavar, BAY43-9006)

23

Los Angeles | California | United States | -118.24368 | 34.05223 New York | New York | United States | -74.00597 | 40.71427 Bruxelles - Brussel | N/A | Belgium | N/A | N/A Bruxelles - Brussel | N/A | Belgium | N/A | N/A Bruxelles - Brussel | N/A | Belgium | N/A | N/A Ghent | N/A | Belgium | 3.71667 | 51.05 Leuven | N/A | Belgium | 4.70093 | 50.87959 Lille | N/A | France | 3.05858 | 50.63297 Marseille | N/A | France | 5.38107 | 43.29695 Paris | N/A | France | 2.3488 | 48.85341 Rennes | N/A | France | -1.67429 | 48.11198 Saint-Herblain | N/A | France | -1.651 | 47.21154 Haifa | Israel | Israel | 34.99928 | 32.81303 Jerusalem | Israel | Israel | 35.21633 | 31.76904 Petah Tikva | Israel | Israel | 34.88747 | 32.08707 Rehovot | Israel | Israel | 34.81199 | 31.89421 Tel Aviv | Israel | Israel | 34.78057 | 32.08088 Tel Litwinsky | N/A | Israel | 34.84588 | 32.05096 Rozzano | Milano | Italy | 9.1559 | 45.38193 Forlì | N/A | Italy | 12.04144 | 44.22177 Milan | N/A | Italy | 12.59836 | 42.78235 Pisa | N/A | Italy | 10.4036 | 43.70853 Verona | N/A | Italy | 10.9938 | 45.43854

0

NCT00044512

[ 2, 3 ]

31

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

null

This phase I/II trial is studying the side effects and best dose of oblimersen when given together with doxorubicin and docetaxel and to see how well they work in treating women with metastatic or locally advanced breast cancer. Drugs used in chemotherapy, such as doxorubicin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of doxorubicin and docetaxel by making the tumor cells more sensitive to the drugs.

PRIMARY OBJECTIVES: I. To evaluate the pharmacokinetics of G3139, doxorubicin and docetaxel in breast cancer patients receiving G3139/AT therapy. (Phase I) II. To determine the safety of bcl-2 antisense oligonucleotide G3139 (GenasenseTM) together with docetaxel plus doxorubicin (AT) in patients with metastatic and locally advanced breast cancer (LABC). (Phase I) III. To determine the therapeutic efficacy of neoadjuvant G3139 in combination with AT chemotherapy in patients with LABC. (Phase II) IV. To further evaluate the safety of bcl-2 antisense oligonucleotide G3139 (GenasenseTM) together with docetaxel plus doxorubicin (AT) in patients with locally advanced breast cancer (LABC). (Phase II) SECONDARY OBJECTIVES: I. To determine the clinical and imaging response to neoadjuvant G3139/AT in the breast and the axillary lymph nodes. (Phase II) II. To determine the disease-free survival of breast cancer patients treated with neoadjuvant G3139/AT. (Phase II) III. To further define the pharmacokinetics of G3139/AT. (Phase II) IV. To evaluate the role of Bcl-2 expression as a predictor of response to neoadjuvant G3139/AT therapy. (Phase II) V. To obtain serial breast cancer samples from patients treated with G3139. (Phase II) OUTLINE: This is an open-label, dose-escalation study of oblimersen. PHASE I (COMPLETED AS OF 8/16/04): Patients receive oblimersen IV continuously on days 1-6 interrupted only to administer doxorubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 6. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-13 or pegfilgrastim SC on day 7. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PHASE II: Patients receive doxorubicin, docetaxel, G-CSF or pegfilgrastim, and oblimersen at the MTD as in phase I. Patients with resectable tumors after 6 courses undergo surgical resection. Patients are followed every 3-6 months for 5 years.

Male Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer

null

1

arm 1: PHASE I (COMPLETED AS OF 8/16/04): Patients receive oblimersen IV continuously on days 1-6 interrupted only to administer doxorubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 6. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-13 or pegfilgrastim SC on day 7. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PHASE II: Patients receive doxorubicin, docetaxel, G-CSF or pegfilgrastim, and oblimersen at the MTD as in phase I. Patients with resectable tumors after 6 courses undergo surgical resection.

[ 0 ]

8

[ 2, 0, 0, 2, 2, 3, 10, 10 ]

intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given SC intervention 5: Given SC intervention 6: Undergo surgical resection intervention 7: Optional correlative studies intervention 8: Optional correlative studies

intervention 1: oblimersen sodium intervention 2: doxorubicin hydrochloride intervention 3: docetaxel intervention 4: filgrastim intervention 5: pegfilgrastim intervention 6: therapeutic conventional surgery intervention 7: pharmacological study intervention 8: laboratory biomarker analysis

1

Houston | Texas | United States | -95.36327 | 29.76328

0

NCT00063934

[ 2, 3 ]

61

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

2MALE

null

RATIONALE: Everolimus may stop the growth of tumor cells by stopping blood flow to the tumor. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining everolimus with gefitinib may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with gefitinib and to see how well they work in treating patients with progressive glioblastoma multiforme or (progressive metastatic prostate cancer closed to accrual 10/19/06).

OBJECTIVES: Primary * Determine the maximum tolerated dose of everolimus when given in combination with gefitinib in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer -closed to accrual as of 10/19/2006). (Phase I) * Determine the safety and efficacy of this regimen in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer - closed to accrual as of 10/19/2006). (Phase II) Secondary * Determine whether a pharmacokinetic interaction exists between everolimus and gefitinib in patients treated with this regimen. * Determine the association between clinical outcomes and markers that may predict sensitivity of a tumor in patients treated with this regimen. * Determine the pharmacodynamic effects of this regimen on post-therapy tumor specimens and peripheral blood mononuclear cells from these patients. OUTLINE: This is a phase I, open-label, non-randomized, dose-escalation study of everolimus followed by a phase II study. * Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Brain and Central Nervous System Tumors Prostate Cancer

adult glioblastoma recurrent prostate cancer recurrent adult brain tumor stage IV prostate cancer adult giant cell glioblastoma adult gliosarcoma

null

1

arm 1: •Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. •Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

[ 0 ]

2

[ 0, 0 ]

intervention 1: None intervention 2: None

intervention 1: everolimus intervention 2: gefitinib

2

New York | New York | United States | -74.00597 | 40.71427 Barcelona | N/A | Spain | 2.15899 | 41.38879

0

NCT00085566

[ 3 ]

95

RANDOMIZED

PARALLEL

2DIAGNOSTIC

0NONE

false

0ALL

false

The goal of this clinical research study is to study how effective treatments with clofarabine alone and clofarabine given in combination with ara-C are in the treatment of leukemia and high-risk myelodysplastic syndrome (MDS) in patients who are 60 years or older. The safety of these treatments will also be compared.

Clofarabine is a chemotherapy drug that is designed to interfere with the growth and development of cancer cells. Ara-C is a chemotherapy drug which is approved for the treatment of AML and MDS. Although there is experience with the combination of both drugs, there have not been trials that explored the particular doses and schedule of clofarabine plus ara-C that you may receive. Before you can start treatment on the study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam. You will also be asked about what medications you are taking currently and about the level of your daily activities. About 2 tablespoons of blood will be collected for routine blood tests and to make sure you are not at increased risk for developing side effects. Before your first treatment (usually within 14 days), you may have bone marrow samples collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. The procedure will be explained to you by your doctor and will require you to sign a separate consent document. Early study results showed that there is clearly a better response with the combination treatment compared to the clofarabine alone treatment. Because of this, all participants in this study will now be assigned to the clofarabine plus ara-C group. You will receive clofarabine through a vein daily for 5 days in a row. In addition, you will receive injections of ara-C under the skin once a day for 14 days in a row. On those days when both clofarabine and ara-C are taken, the clofarabine will be given approximately 4 hours before the ara-C injections. You can be taught to give the ara-C injections to yourself. Each cycle may be repeated every 3 to 6 weeks. You will be required to record the injections in a medication diary. Up to 2 of these cycles (for both groups) can be given at this dose schedule. If you show a response to treatment, you can continue with up to 12 cycles of therapy, during which clofarabine will be given for 3 days instead of 5 and ara-C for 7 days instead of 14. Maintenance courses may be given on average every 4 to 7 weeks. Before every treatment course, you will have a physical exam including measurement of your weight and vital signs. You will also be asked how you are feeling and how you are able to go about your daily routine. At least once a week (more often if your doctor feels it is necessary), you will have blood samples (about 1-2 teaspoons) collected for routine lab tests. Around 3 weeks after your first treatment, you may have samples of bone marrow collected. After that, the bone marrow collections will be performed every 2 weeks (or more often if your doctor feels it is necessary). The bone marrow sample will be tested to evaluate the response of the disease to therapy. You will need to stay in Houston for the first 4 weeks of treatment. After that, you have to return to Houston to receive the clofarabine treatment, but you can have check-up visits and blood tests with your local doctor. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you. After you finished your treatment, and as long you are participating on this study you will be scheduled every 3-6 months to check on the status of the disease and your overall health as long as you stay on the study. Once you are taken off the study, your doctor will decide how often you will have follow-up as part of your standard care. This is an investigational study. Clofarabine is authorized by the Food and Drug Administration (FDA) for use in research only. Up to 108 participants will take part in this study. All will be enrolled at M. D. Anderson.

Acute Myeloid Leukemia Myelodysplastic Syndrome

Acute Myeloid Leukemia AML High-Risk Myelodysplastic Syndrome MDS Clofarabine Cytarabine ara-C

null

2

arm 1: Clofarabine intravenous (IV) 30 mg/m\^2 daily times 5 days arm 2: Clofarabine IV 30 mg/m\^2 daily times 5 days + Ara-C 20 mg/m\^2 subcutaneously daily times 14 days.

[ 1, 1 ]

2

[ 0, 0 ]

intervention 1: 1-hour IV infusion 30 mg/m\^2 daily times 5 days (Days 1-5) intervention 2: 20 mg/m\^2 subcutaneously daily times 14 days (Days 1-14). On Days 1 to 5 of each course, clofarabine will precede injection of ara-C by approximately 4 hours (+/- 1 hour).

intervention 1: Clofarabine intervention 2: Ara-C

1

Houston | Texas | United States | -95.36327 | 29.76328

0

NCT00088218

[ 0 ]

6

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

null

RATIONALE: Herpesvirus is found in the lesions of most patients with Kaposi's sarcoma, and may have a role in causing Kaposi's sarcoma. Valganciclovir is an antiviral drug that acts against many types of herpesviruses and may be an effective treatment for Kaposi's sarcoma. PURPOSE: This clinical trial is studying how well valganciclovir works in treating patients with classic non-HIV-associated Kaposi's sarcoma.

OBJECTIVES: Primary * Determine the antitumor activity of valganciclovir in patients with classic non-HIV-associated Kaposi's sarcoma (KS). Secondary * Determine the effect of this drug on lytic and latent human herpesvirus-8 gene expression in KS lesions of these patients. * Determine the effect of this drug on the markers of angiogenesis in KS lesions of these patients. * Determine the safety and tolerability of this drug in these patients. OUTLINE: This is a pilot study. Patients receive oral valganciclovir twice daily for 3 weeks and then once daily for 21 weeks in the absence of disease progression or unacceptable toxicity. All patients are followed for 1 month after completion of therapy. Patients with responding disease are followed monthly for up to 1 year. PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study within 1 year.

Sarcoma

classic Kaposi sarcoma recurrent Kaposi sarcoma

null

1

arm 1: Patients receive oral valganciclovir twice daily for 3 weeks and then once daily for 21 weeks in the absence of disease progression or unacceptable toxicity. All patients are followed for 1 month after completion of therapy. Patients with responding disease are followed monthly for up to 1 year.

[ 0 ]

1

[ 0 ]

intervention 1: None

intervention 1: valganciclovir

3

0

NCT00096538

[ 3 ]

67

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

false

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gemcitabine together with paclitaxel may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with paclitaxel works in treating patients with persistent, recurrent, or metastatic head and neck cancer.

OBJECTIVES: * Determine overall and progression-free survival probability in patients with persistent, recurrent, or metastatic squamous cell carcinoma of the head and neck treated with gemcitabine and paclitaxel. * Determine the confirmed and unconfirmed response (partial and complete) probability in patients with measurable disease treated with this regimen. * Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive gemcitabine IV over 30 minutes and paclitaxel IV over 1 hour on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 4 additional courses beyond CR. Patients are followed every 8 weeks until disease progression, every 6 month for 2 years, and then annually for 1 year. PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study within 10-13 months.

Head and Neck Cancer

Recurrent stage IV squamous cell carcinoma hypopharynx larynx lip oral cavity nasopharynx oropharynx paranasal nasal cavity metastatic neck cancer

null

1

arm 1: None

[ 0 ]

2

[ 0, 0 ]

intervention 1: 3,000 mg/m2 IV over 30 minutes on days 1 and 15 (q28 days). intervention 2: 150 mg/m2 IV over 1 hour on days 1 and 15 (q 28 day cycle), administered after gemcitabine

intervention 1: gemcitabine intervention 2: paclitaxel

123

0

NCT00100789

[ 3 ]

12

NON_RANDOMIZED

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

true

The purpose of this study is to find out what the response is and the side effects are with chemotherapy using a combination of drugs called D.T. PACE (Dexamethasone, Thalidomide, cis-Platinum, Adriamycin, Cyclophosphamide, and Etoposide) + Rituxan, followed by two autologous transplants.

Approximately 25 patients, male or female, age 18 and older, regardless of race or ethnicity, will participate in this study at UAMS (University of Arkansas for Medical Sciences) only. Participants will receive two courses of chemotherapy with a regimen called DT PACE + Rituxan. This regimen consists of 6 drugs: Dexamethasone, Thalidomide, cis-Platinum, Adriamycin, Cyclophosphamide, and Etoposide.

Waldenstrom Macroglobulinemia

Waldenstrom

null

1

arm 1: None

[ 0 ]

1

[ 0 ]

intervention 1: INDUCTION PHASE DT PACE + Rituxan DT PACE + Rituxan + PBSC Collection Response Assessment TRANSPLANT PHASE Transplant 1 (MEL 200 (patients with \< 50% response to induction) OR MEL-DT PACE (Patients with \> 50% response to Induction) Transplant 2 (identical to the first, except patients with progressive or proliferative disease, will receive BEAM) MAINTENANCE PHASE Rituxan every 3 months x 1 year

intervention 1: DT PACE + Rituxan

1

Little Rock | Arkansas | United States | -92.28959 | 34.74648

0

NCT00107614

[ 3 ]

17

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

2MALE

null

This phase II trial is studying how well 17-AAG works in treating patients with metastatic prostate cancer that did not respond to previous hormone therapy. Drugs used in chemotherapy, such as 17-AAG, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVES: I. Determine the prostate-specific antigen (PSA) response in patients with hormone-refractory metastatic prostate cancer treated with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). SECONDARY OBJECTIVES: I. Determine the overall survival and disease-free survival rate in patients treated with this drug. II. Determine the safety profile of this drug in these patients. III. Determine the duration of PSA response and PSA control in patients treated with this drug. IV. Determine the partial and complete response rates in patients with measurable disease treated with this drug. V. Correlate changes in expression levels of interleukin-6, maspin, and NF-kappaB in serum and tissue with cancer and treatment-related outcomes in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 2-6 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 2 additional courses of treatment beyond documentation of CR. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 16-28 patients will be accrued for this study within 20 months.

Adenocarcinoma of the Prostate Recurrent Prostate Cancer Stage IV Prostate Cancer

null

1

arm 1: Patients receive 17-N-allylamino 17-demethoxygeldanamycin (17-AAG) IV over 2-6 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 2 additional courses of treatment beyond documentation of CR.

[ 0 ]

2

[ 0, 10 ]

intervention 1: Given IV intervention 2: Correlative studies

intervention 1: tanespimycin intervention 2: laboratory biomarker analysis

1

Rochester | Minnesota | United States | -92.4699 | 44.02163

0

NCT00118092

[ 5 ]

130

RANDOMIZED

PARALLEL

1PREVENTION

0NONE

false

0ALL

true

The investigators hypothesize that the medication amiodarone decreases the incidence of atrial fibrillation (AF) following non-cardiac open-chest surgery. Their specific aims are to: * Determine the effectiveness of amiodarone for the prevention of AF following non-cardiac open-chest surgery; * Determine the influence of the prevention of AF following non-cardiac thoracic surgery on post-surgical duration of stay in the Intensive Care Unit (ICU); post-surgical duration of stay in a hospital unit that employs cardiac monitoring; and duration of post-surgical hospital stay; and * Determine the safety of amiodarone for the prevention of AF following non-cardiac open-chest surgery.

Thousands of patients undergo major non-cardiac open-chest surgery in the United States each year. These surgeries most often consist of lung surgery, in which one lobe of the lung is removed (lobectomy) or the entire lung is removed (pneumonectomy). A major complication of these non-cardiac open-chest surgeries is the occurrence of an irregular heartbeat known as atrial fibrillation (AF), which develops in up to 40% of patients undergoing these procedures. AF is characterized by rapid, irregular, chaotic beating of the two smaller chambers of the heart (the atria), leading to rapid, irregular beating of the two larger chambers (the ventricles). The average time to occurrence of post-surgical AF is 2-3 days following surgery. AF occurring following major non-cardiac open-chest surgery can result in extremely rapid heart rates, as fast as 150-200 beats per minute, and may be associated with serious consequences, including severely low blood pressure and potentially debilitating stroke. Further, the risk of death following non-cardiac open-chest surgery is significantly higher in patients who develop AF compared with those who do not. Therefore, the occurrence of this irregular heartbeat following non-cardiac open-chest surgery is associated with severe, potentially life-threatening consequences. Prevention of this irregular heartbeat in these patients may therefore be very important. Amiodarone is a medication that is known to be effective for prevention and treatment of AF that occurs in patients who have not undergone surgery. In addition, amiodarone has been shown to be effective for prevention of AF following open-chest heart surgery. However, the use of medications for prevention of AF following non-cardiac open-chest surgery has not been well studied, and amiodarone has not been studied in a controlled trial for the prevention of AF in patients undergoing these procedures. In addition, amiodarone is associated with side effects, and it is important to determine the safety of this medication when used in this patient population.

Atrial Fibrillation

amiodarone atrial fibrillation surgical procedures, thoracic

null

2

arm 1: Amiodarone 1050 mg via continuous intravenous infusion for 24 hours followed by 400 mg orally twice daily for 6 days arm 2: Patients in this group receive no intervention

[ 0, 4 ]

1

[ 0 ]

intervention 1: None

intervention 1: Amiodarone

1

Indianapolis | Indiana | United States | -86.15804 | 39.76838

0

NCT00127712

[ 3 ]

18

NON_RANDOMIZED

SINGLE_GROUP

1PREVENTION

0NONE

false

0ALL

true

Velcade (bortezomib, PS-341) has recently been approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma for patients who have received at least one prior therapy. Velcade is a unique compound developed by scientists at Millennium Pharmaceuticals, Inc. Velcade enters cells and affects the way they divide. Cancer cells are particularly sensitive. Velcade interferes with the enzyme "proteasome" which is responsible for allowing cells to divide. When cancer cells cannot divide, they die. Velcade falls into the class of drugs known as "proteasome inhibitors."

Studies at the Myeloma Institute for Research \& Therapy have shown that Velcade is very effective in treating patients who are relapsing after having been treated with at least two lines of prior therapy. One key factor in multiple myeloma is bone destruction caused by the myeloma cells. Most patients with multiple myeloma (80%) will develop skeletal lesions, despite treatment. These lesions are rarely repaired, even when the myeloma is in remission. Experience at MIRT has suggested that Velcade may increase osteoblast (bone cells that cause bone growth) activity. One goal of this study is to identify if Velcade's effect on myeloma is due to its ability to increase osteoblasts. This study also has the following goals: * To find out the lowest dose of Velcade that has an effect on myeloma and also increases bone activation; * To identify ways to predict if Velcade will increase bone activation. Time periods are: According to cohort assignment, you will receive three cycles of Velcade®™ (1.3 mg/m2, 1.0 mg/m2 or 0.7 mg/m2) on days 1, 4, 8, and 11, on a 21-day cycle. During the first two cycles of Velcade®™, bone markers (tests on your bones) will be measured Days 1, 4, 8, 11: Pre-dose, post-dose, and every 2 to 4 hours for 8 hours. Days 2-3, 5-7, 9-10, 12-21: every 24 hours, beginning with the immediate post-dose sample (+/- 2 hours) During the third cycle of Velcade®™, bone markers will be measured Days 1 and 11: Pre-dose and post-dose, and then again on Day 21.

Multiple Myeloma

null

3

arm 1: Treatment: 1.3 mg/m\^2 arm 2: Treatment: 1.0 mg/m\^2 arm 3: Treatment: 0.7 mg/m\^2

[ 0, 0, 0 ]

1

[ 0 ]

intervention 1: Patients will receive two cycles of VELCADE™ (1.3 mg/m2, 1.0 mg/m2 or 0.7 mg/m2) on days 1, 4, 8, and 11, on a 21 day cycle. No growth factors or bisphosphonates will be allowed during study treatment. Bone markers will be measured: Days 1, 4, 8, 11: Pre-dose, post-dose, and every 2-4 hours for 8 hours Days 2-3, 5-7, 9-10, 12-21: every 24 hours, beginning with the immediate post-dose sample (+/- 2 hours) Other laboratory and radiologic studies will be performed as detailed in the Study Calendar. Patients will complete the study after two cycles of VELCADE™. However, if a patient continues to receive VELCADE™ as part of his/her treatment for relapsing MM, routine bone markers may be monitored for the duration of VELCADE™ treatment as clinically indicated.

intervention 1: VELCADE™

1

Little Rock | Arkansas | United States | -92.28959 | 34.74648

0

NCT00128921

[ 4 ]

1,056

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

0ALL

true

The purpose of the study is to determine whether treatment with sulodexide is effective in reducing the level of urine albumin excretion in patients with early diabetic kidney disease expressed as microalbuminuria.

Diabetic nephropathy is an important cause of morbidity and mortality in patients with either type 1 or type 2 diabetes mellitus. The pathogenesis and natural history of diabetic nephropathy is characterized initially by microalbuminuria followed by a progressive decline in glomerular function. An emerging body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve pathobiochemical alterations of glycoproteins in these structures. Evidence, in experimental animals rendered diabetic, reveals that the administration of heparin and other anionic glycoproteins (GAG) can effectively prevent the biochemical alterations which are responsible for albuminuria. Sulodexide, an orally active agent which does not have anticoagulant properties associated with its oral dose range, is comprised of three naturally occurring glycosaminoglycan (GAG) polysaccharide components isolated from porcine intestinal mucosa. Small clinical studies employing sulodexide, have shown that albuminuria is significantly diminished in patients with diabetic nephropathy, even when these patients are receiving angiotensin II receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI), agents already proven to reduce albuminuria and slow progressive diabetic nephropathy. This study is designed to evaluate whether sulodexide is safe and effective in treating subjects with type 2 diabetic nephropathy. Subjects with type 2 diabetes and microalbuminuria (defined as a urinary albumin to creatinine ratio,(ACR)in men 35-200 mg/G and in women 45-200 mg/G) who are also receiving either irbesartan 300 mg/day, losartan 100 mg/day, or a maximum approved dose of an angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEI) will be enrolled in the study. The study will consist of the following periods: * Screening: of 1-2 weeks for assessing basic eligibility/exclusion criteria * Run-in: of up to 16 weeks on maximal dose of ARB or ACE with stable blood pressure control * Qualifying visit: qualifying patients are on maximal dose of ARB or ACE for a minimum of 4 months with stable BP control, SBP \<150 mmHg, DBP \<90 mmHg and albumin to creatinine ratio, (ACR) between in men 35-200 mg/G and in women 45-200 average of 3 first morning voids * Randomization: patients are randomized to sulodexide 100 mg or matching placebo administered orally twice a day. * Maintenance: 26 week maintenance period, with 4 visits to monitor safety and ACR * Washout Period: 8 week washout period, with 2 visits to monitor safety and ACR

Diabetic Nephropathy

Diabetes Diabetes Mellitus, Type 2 Albuminuria Diabetic Nephropathy

null

2

arm 1: Also known as KRX-101. All patients will be on standard of care ACE or ARBs. arm 2: All patients will be on standard of care ACE or ARBs.

[ 0, 2 ]

2

[ 0, 0 ]

intervention 1: 100 mg sulodexide gelcaps intervention 2: 0 mg gelcap

intervention 1: Sulodexide intervention 2: Placebo

3

0

NCT00130208

[ 4 ]

581

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

1FEMALE

null

Osteoporosis prevention is important in patients with osteopenia (low bone density). This study will test the safety and efficacy of zoledronic acid in patients diagnosed with osteopenia.

null

Osteopenia

Postmenopausal osteoporosis osteopenia zoledronic acid Osteopenia (osteoporosis prevention)

null

3

arm 1: Zoledronic acid 5 mg intravenous (i.v.) given at randomization and Month 12 arm 2: Zoledronic acid 5 mg intravenous (i.v.) given at randomization and placebo at Month 12 arm 3: Placebo given at randomization and Month 12

[ 0, 0, 2 ]

2

[ 0, 0 ]

intervention 1: Zoledronic acid 5 mg intravenous intervention 2: Physiologic 0.9% normal saline

intervention 1: Zoledronic Acid intervention 2: Placebo

1

East Hanover | New Jersey | United States | -74.36487 | 40.8201

0

NCT00132808

[ 2, 3 ]

16

NON_RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

false

The purpose of this study is to: 1) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the absence of planned growth factor support with granulocyte colony-stimulating factor (G-CSF) (Patients with HER-2/neu positive disease may receive Herceptin, and 2) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the presence of planned growth factor support with G-CSF.

null

Stage IV (Metastatic) Breast Cancer

Breast cancer

null

3

arm 1: Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned. arm 2: Weekly intravenous infusion of 80 mg/m\^2 ABI-007, followed by an infusion of 15 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given. arm 3: Weekly intravenous infusion of 90 mg/m\^2 ABI-007, followed by an infusion of 20 mg/m\^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.

[ 0, 0, 0 ]

4

[ 0, 0, 0, 2 ]

intervention 1: Weekly intravenous infusions over 30 minutes. intervention 2: Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor. intervention 3: Trastuzumab was administered to participants who had HER-2-neu positive tumors. Participants received trastuzumab by IV infusion via a vascular access device following dosing with ABI-007 and vinorelbine. During their first cycle, 4 mg/kg was administered on day 1 of that cycle as a loading dose. During subsequent weekly treatments, 2 mg/kg was administered. Trastuzumab is commercially available and was not supplied by the Sponsor. intervention 4: During Part 1, participants followed a dosing regimen with ABI-007 and vinorelbine without G-CSF treatment. However, G-CSF was allowed for administration as necessary in accordance with commonly accepted clinical guidelines. In Part 2, participants started G-CSF treatment in concurrence with their ABI-007 and vinorelbine treatments. G-CSF was administered to all participants on Days 2-7 of each cycle, at a dose of 5 mcg/kg. If the participant's absolute neutrophil (ANC) count was \>20,000/mm\^3 on the day of anticipated chemotherapy, the site staff reduced the daily dose of G-CSF by 50% to 2.5 mcg/kg. G-CSF is commercially available and was not supplied by the Sponsor.

intervention 1: ABI-007 intervention 2: vinorelbine intervention 3: Trastuzumab intervention 4: G-CSF

2

0

NCT00140140

[ 3 ]

25

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

true

The purpose of this study is to determine the percentage of people who can attain remission and the length of time such responses to therapy are sustained, as well as the side effects that might result from rituximab and thalidomide in people with lymphoplasmacytic lymphoma.

* Patients will receive thalidomide(200mg) orally once daily for two weeks. If after two weeks of thalidomide, the patient is doing well the dose of thalidomide will increase (400mg) and they will remain on it for up to 50 additional weeks. The length of time a patient is on thalidomide will depend upon how they are responding to therapy. * During the second week of the study patients will also begin receiving rituximab intravenously once weekly for 4 weeks, which may then be repeated 8 weeks later depending upon the response. * A determination of how the patient is responding will be made based on testing conducted at 12 weeks. This testing includes blood tests and possibly a bone marrow biopsy. If it is determined that the disease is not progressing, patients will begin a second phase of treatment which includes 4 additional weekly infusions of rituximab and the continuation of oral thalidomide. * If it is determined at the 12-week evaluation, or at any time thereafter, that the disease has progressed (by studying serum immunoglobulin M (IgM) levels, bone marrow involvement, tumor cells, and/or development of new signs and symptoms) then the patient will be removed from the study. * Periodic examinations and tests will be done to determine how the patient is doing, what response and side effects (if any) the patient may be having from the study drugs. If patient is responding to therapy then they will remain on this study and followed for a period of two years. * Bone marrow biopsies and aspirations will be obtained at 3-6 month intervals extending for 2 years following the last treatment.

Waldenstrom's Macroglobulinemia Lymphoplasmacytic Lymphoma

thalidomide rituximab Waldenstrom's

null

1

arm 1: Thalidomide 200mg orally once a day for 14 weeks if that dosage is tolerated well, it will be increased to 400mg for up to 50 weeks Rituximab Given intravenously once weekly for 4 weeks beginning the second week of study treatment. If tolerated well, this may be repeated 8 weeks later.

[ 0 ]

2

[ 0, 0 ]

intervention 1: 200mg orally once a day for 14 weeks if that dosage is tolerated well, it will be increased to 400mg for up to 50 weeks. intervention 2: Given intravenously once weekly for 4 weeks beginning the second week of study treatment. If tolerated well, this may be repeated 8 weeks later.

intervention 1: Thalidomide intervention 2: Rituximab

2

0

NCT00142116

[ 4 ]

10,917

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

null

The aim of this study is to test whether ivabradine is able to reduce cardiovascular events when given to patients with coronary artery disease and impaired heart function.

null

Coronary Disease Ventricular Dysfunction, Left

null

2

arm 1: None arm 2: None

[ 0, 2 ]

2

[ 0, 0 ]

intervention 1: None intervention 2: None

intervention 1: Ivabradine intervention 2: Placebo

1

London | N/A | United Kingdom | -0.12574 | 51.50853

0

NCT00143507

[ 2 ]

24

NON_RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

null

Determine single dose pharmacokinetic parameters of olmesartan in pediatric patients with hypertension in ages 12 months - 16 years

null

Hypertension

Olmesartan PK in children

null

1

arm 1: Children less than 6 years old received 0.3 mg/kg. Children 6 years old or older received 40 mg, if they weighed 35 kg or more; 20 mg if they weighed less than 35 kg.

[ 0 ]

1

[ 0 ]

intervention 1: Children less than 6 years old: oral suspension or tablets equal to 0.3 mg/kg; 20 mg or 40 mg tablets for older children depending on weight.

intervention 1: Olmesartan medoxomil

5

0

NCT00151814

[ 5 ]

20

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

0ALL

true

We want to assess whether "how and when" one takes sleep medication results in similar or different outcomes with respect to symptom relief. We also want to know whether taking medication for a period of time provides continued benefit once the medication is stopped.

To date, the aggressive treatment (Tx) of chronic insomnia has been evaluated in terms of whether maintenance therapy is possible. While what constitutes maintenance therapy is a matter of debate, there are two studies which show that benzodiazepine receptor agonists (BZRAs) 1) are effective when used intermittently for up to 3 months and 2) may be used on a nightly basis for up to 6 months with no loss of efficacy. The significance of the present research is two fold. First, it will allow us to compare the two primary strategies used for long term treat of insomnia (nightly dosing vs intermittent dosing). Second, it will allow an evaluation of the possibility that extended treatment, given careful withdrawal from medication, may yield long term clinical gains. Re: Objective 1: It is widely assumed that intermittent dosing confers increased efficacy. That is, less frequent medication use will extend the duration of time for which the medication is maximally potent. An empirical assessment of this proposition is required. If incorrect, physicians and patients should be encouraged to adopt a more aggressive approach to treatment. If correct, physicians and patients should be encouraged to adopt the intermittent dosing approach to treatment. Re: Objective 2: It is widely assumed that treatment with sedatives (sleep promoting medications) constitutes only palliative care. An empirical assessment of this proposition is required. If correct, physicians and patients should be encouraged to adopt a more aggressive approach to long term treatment. If incorrect, physicians and patients should be encouraged to adopt an approach to treatment that is not currently a standard of practice: extended treatment with a clear plan to taper medication that is designed to maintain the clinical gains that occurred with medication use. We propose to evaluate the above issues in a pilot study of 40 subjects with Primary Insomnia where subjects are randomized to one of 4 conditions: 1. QHS dosing with placebo 2. QHS dosing with 10mg of zolpidem 3. Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed) 4. Monitor only condition.

Insomnia Primary Insomnia Psychophysiologic Insomnia

Insomnia Sleep zolpidem Ambien Hypnotics

null

4

arm 1: QHS dosing with placebo (i.e. nightly dose) arm 2: QHS dosing with 10mg of zolpidem (i.e. nightly dose) arm 3: Intermittent dosing with 10mg of zolpidem (3-5 pills per week as needed arm 4: Monitor only condition (no placebo, no drug).

[ 2, 1, 0, 4 ]

2

[ 0, 0 ]

intervention 1: 10 mg of Zolpidem intervention 2: None

intervention 1: Zolpidem intervention 2: Sugar Pill

1

Rochester | New York | United States | -77.61556 | 43.15478

0

NCT00156533

[ 0 ]

45

RANDOMIZED

PARALLEL

9OTHER

3TRIPLE

true

0ALL

false

The purpose of this study is to examine prospectively the safety and efficacy of alefacept in the treatment of subjects with severe alopecia areata of the scalp. Common features between psoriasis and alopecia areata, including immunologic and therapeutic aspects, suggest that alefacept, which has been shown to be a safe and statistically significant beneficial therapeutic modality for the treatment of psoriasis, may have therapeutic value in alopecia areata.

Alopecia areata (AA) is an autoimmune condition characterised by a T-cell mediated attack on the hair follicle. The inciting antigenic stimulus is unknown. A dense peribulbar lymphocytic infiltrate and reproducible immunologic abnormalities are hallmark features of the condition. The cellular infiltrate primarily consists of activated T-lymphocytes and antigen-presenting Langerhans cells. T-lymphocytes play a critical role in the pathogenesis of disease. The observance of hair regrowth in those with alopecia areata who are treated with cyclosporine, a known inhibitor of T-cell function, further confirms the central role of the T-lymphocytes in the development of the disease. Activation of T-cells is initiated by interaction of the T-cell receptor with the antigen/major histocompatibility complex on the antigen-presenting cells. Co-stimulatory interactions occur secondarily, including binding of the T-cell CD2 receptor to the antigen-presenting cell ligand LFA-3 (lymphocyte function-associated antigen-3 CD58). Induction of a molecular signaling cascade with resultant T-cell activation and proliferation ensues. Abrogation of this activation may result in diminished or aborted expression of disease, and thus suggests a potential therapeutic role for alefacept in the treatment of alopecia areata. Alefacept is a bioengineered LFA-3/Immunoglobulin fusion protein that binds to the CD2 T-cell receptor and interferes with the ligation of LFA-3. Binding of the immunoglobulin portion of the fusion protein to the FCy receptor on antigen-presenting cells potentiates apoptosis of CD-2 T-cells to thereby reduce the population of activated T-cells. Psoriasis is a T-cell mediated disorder that shares many immunologic features with alopecia areata. Accordingly, treatments that are effective in psoriasis often prove to be beneficial in alopecia areata. Anthralin, topical and intralesional steroids and cyclosporine are among several therapeutic agents that have efficacy in both disorders. Based on the impressive therapeutic responses seen in those with psoriasis treated with alefacept, a similarly beneficial outcome is tentatively anticipated with treatment of those with alopecia areata.

Alopecia Areata

null

2

arm 1: None arm 2: None

[ 0, 2 ]

1

[ 0 ]

intervention 1: Study participants will receive weekly IM administration of placebo or 15 mg of alefacept for 12 weeks, to be followed by a 12-week post-treatment period during which the safety, efficacy, and durability of effect in treatment responders will be assessed on weeks 2, 4, 8 and 12.

intervention 1: Alefacept

1

Minneapolis | Minnesota | United States | -93.26384 | 44.97997

0

NCT00167102

[ 3 ]

18

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

true

This study is a pilot study to evaluate the feasibility and safety of conducting a year long, double-blind, placebo-controlled trial of fluoxetine in pre-school children to enhance developmental processes in core areas impacted by autism.

Autism, a brain disorder that affects a small percentage of Americans, often results in a lifetime of impaired thinking, feeling, and social functioning. The disorder generally becomes apparent in children by the age of 3. Autism typically affects a person's ability to communicate, form relationships with others, and respond appropriately to the external world. Some people with autism can function at a relatively high level, with speech and intelligence intact. Others have serious cognitive impairments and language delays, and some never speak. This study will assess the safety and effectiveness of treating autistic children with fluoxetine to enhance developmental processes in core areas impacted by autism. Each participant was randomly assigned to treatment with double-blinded placebo or fluoxetine for 12 months. After initial screening and randomization, participants were assessed every two weeks for approximately the first 3 months, or until the dose of medication is stabilized. After this initial period, they were assessed on a monthly basis. Dosing was flexible as determined by the adverse and beneficial responses to treatment although there was a suggested titration schedule.

Autistic Disorder

Autism

null

2

arm 1: Placebo, liquid solution flexible dose 0.5 to 5ml every morning (AM) arm 2: Fluoxetine, 20mg/5ml solution, flexible dose 0.5 to 5ml every AM

[ 2, 0 ]

2

[ 0, 0 ]

intervention 1: Between 2 mg per day and 20 mg per day of liquid fluoxetine will be given in the morning using a flexible dosing strategy, following a 36-week dose titration schedule. intervention 2: Between 0.5ml per day and 5ml per day of liquid placebo will be given in the morning using a flexible dosing strategy, following a 36-week dose titration schedule.

intervention 1: Fluoxetine intervention 2: Placebo

2

0

NCT00183339

[ 0 ]

11

RANDOMIZED

PARALLEL

1PREVENTION

3TRIPLE

false

0ALL

false

The purpose of this study is to determine whether taking the medication memantine reduces impairment of memory and attention associated with electroconvulsive therapy.

The primary objective of this study is to determine whether the novel NMDA antagonist memantine, FDA approved for use in moderate to severe alzheimers dementia, may reduce the neurocognitive deficits associated with right unilateral ECT treatments in patients receiving ECT for a severe and relatively refractory Major Depressive episode. Our hypothesis is that the use of an NMDA antagonist would reduce intracellular calcium levels, and glutamatergic stimulation during ECT. This reduction in excitatory stimulation during ECT would reduce hippocampal and prefrontal neuronal endangerment and dysfunction, thereby reducing cognitive impairment associated with right unilateral ECT treatments. We also hypothesize that ACTH and cortisol levels will correlate with neurocognitive impairment in placebo treated subjects, but not in the memantine treated individuals.

Depressive Disorder, Major

null

2

arm 1: Patients received a placebo capsule starting the day before ECT begins and while receiving ECT arm 2: Patients receive memantine starting the day before ECT begins and while receiving ECT

[ 2, 0 ]

2

[ 0, 0 ]

intervention 1: Patients received a memantine containing capsule starting the day before ECT begins and while receiving ECT intervention 2: Patients received a placebo capsule starting the day before ECT begins and while receiving ECT

intervention 1: memantine intervention 2: Placebo Oral Capsule

1

Stanford | California | United States | -122.16608 | 37.42411

0

NCT00186498

[ 4 ]

151

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

false

Double blinded clinical trial placebo controlled in 153 children (planned enrollment) with recent diagnosis of ADHD. Patients will be randomized to atomoxetine or placebo arm (2:1). The double blinded period will last 12 weeks and the treatment open phase will last up to 1 year, and atomoxetine treatment will be administered. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.

null

Attention Deficit Hyperactivity Disorder

null

2

arm 1: atomoxetine: 0.5 mg/kg/day every day (QD),by mouth (PO) for 2 weeks, 1.2 - 1.4 mg/kg/day QD, PO for 10 weeks, then 1.2 - 1.4 mg/kg/day QD, PO for up to 1 year arm 2: placebo every day (QD), by mouth (PO) for 12 weeks,then possibility to switch to atomoxetine at 0.5 mg/kg/day QD, PO for 1 week, then to 1.2 - 1.4 mg/kg/day QD, PO for up to 1 year (open-label extension)

[ 0, 2 ]

2

[ 0, 0 ]

intervention 1: None intervention 2: None

intervention 1: Atomoxetine Hydrochloride intervention 2: placebo

11

Badajoz | N/A | Spain | -6.97061 | 38.87789 Barcelona | N/A | Spain | 2.15899 | 41.38879 Donostia / San Sebastian | N/A | Spain | -1.97499 | 43.31283 Espluges de Llobregat | N/A | Spain | N/A | N/A Madrid | N/A | Spain | -3.70256 | 40.4165 Palma de Mallorca | N/A | Spain | 2.65024 | 39.56939 Sabadell | N/A | Spain | 2.10942 | 41.54329 Sant Joan d'Alacant | N/A | Spain | -0.43623 | 38.40148 Santa Cruz de Tenerife | N/A | Spain | -16.25462 | 28.46824 Terrassa | N/A | Spain | 2.01667 | 41.56667 Valencia | N/A | Spain | -0.37966 | 39.47391

0

NCT00191945

[ 4 ]

54

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

true

0ALL

true

Double-Blind, Placebo-Controlled Divalproex Sodium ER in Bipolar I or Bipolar II Depression Previously Diagnosed and Treated as Recurrent Major Depression: This study recruits males and females aged 18 - 70 who currently meet diagnostic criteria for bipolar I or bipolar II disorder and are currently experiencing an episode of major depression. Patients are randomized to double-blind treatment with divalproex sodium ER or placebo and remain in the study for up to six weeks. This six-week double-blind treatment period is followed by an open-label treatment period of six months duration. This study is sponsored by Abbott Laboratories.

null

Bipolar Disorder

null

2

arm 1: None arm 2: None

[ 0, 2 ]

2

[ 0, 0 ]

intervention 1: Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher. intervention 2: . Tablets will be available in 250mg and 500mg strengths. Divalproex will be titrated to a minimum blood level of 50 mg/L. However, the investigators will titrate divalproex to the maximum tolerable dose with an expected average dose of 2000mg per day. By dosing in this manner, all subjects will have a minimum blood level of 50 mg/L, but the mean level is likely to be considerably higher.

intervention 1: Divalproex Sodium ER intervention 2: Placebo

1

Cleveland | Ohio | United States | -81.69541 | 41.4995

0

NCT00194116

[ 4 ]

87

RANDOMIZED

CROSSOVER

0TREATMENT

4QUADRUPLE

false

0ALL

true

The purpose of this trial is to determine whether regularly scheduled use of an inhaled long-acting beta agonist (salmeterol) in the setting of concomitant use of inhaled corticosteroids (beclomethasone hydroflouroalkane (HFA) inhaler) will have a detrimental effect on asthma control in people who bear the B16-Arg/Arg genotype of the beta-2 adrenergic receptor gene, as compared to people with asthma of similar severity who bear the B16-Gly/Gly genotype.

BACKGROUND: The purpose of this study is to compare the effects of a long-acting beta agonist in patients with asthma receiving inhaled corticosteroids who express two distinct polymorphisms of the beta-2 adrenergic receptor. DESIGN NARRATIVE: Participants were homozygous for arginine or glycine at the 16th amino-acid position of the β-2 adrenergic receptor (B16 Arg/Arg or B16 Gly/Gly). Individuals were matched against their opposite genotype by forced expiratory volume in one second (FEV1) and race. Matched participants entered an 8-week run-in period. This is a 62-week crossover design where subjects receive the following therapies: * Beclomethasone HFA (240 µg twice a day (BID)) + as-needed (PRN) albuterol: 8-week run-in * Beclomethasone HFA (240 µg BID) + salmeterol (50 µg BID) + PRN ipratropium bromide + PRN albuterol: 18-week treatment period * Beclomethasone HFA (240 µg BID) + PRN albuterol: 8-week run-out * Beclomethasone HFA (240 µg BID) + placebo salmeterol + PRN ipratropium bromide + PRN albuterol: 18-week treatment period * Beclomethasone HFA (240 µg BID) + PRN albuterol: 10-week run-out The order of treatments received during the two treatment periods is randomized.

Asthma

null

2

arm 1: B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone hydroflouroalkane (HFA), followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA arm 2: B16 Gly/Gly genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

[ 0, 0 ]

2

[ 0, 0 ]

intervention 1: 50 micrograms (mcg) twice per day (BID) (Serevent 50 mcg diskus, GlaxoSmithKline (GSK), North Carolina) intervention 2: 240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)

intervention 1: salmeterol intervention 2: beclomethasone HFA

7

0

NCT00200967

[ 0 ]

59

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

0ALL

true

The purposes of this study are: * to evaluate the efficacy and tolerability of the drug prazosin compared to placebo for combat stress-related nightmares, sleep disturbance and overall function in recently combat-exposed returnees from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). * to evaluate the effects of the selective serotonin reuptake inhibitor (SSRI) paroxetine on behavioral symptoms and overall function in this population.

Trauma-related nightmares and sleep disruption that follow combat exposure are distressing and frequently treatment resistant symptoms that impair quality of life and overall function. These symptoms closely resemble core nighttime symptoms of posttraumatic stress disorder (PTSD), and are increasingly recognized in returnees from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). Prazosin, a generically available brain active alpha-1 adrenergic receptor antagonist, markedly reduced or eliminated combat trauma-related nightmares and sleep disruption in 23 of 25 combat-exposed returnees from OIF at Madigan Army Medical Center (MAMC). The use of prazosin in OIF returnees was based on clinical efficacy of prazosin for trauma-related nightmares, sleep disturbance, and overall function in Vietnam combat veterans with chronic PTSD. The only drugs FDA approved for PTSD are the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine. However, SSRI effectiveness in combat trauma PTSD, especially for nighttime symptoms, remains questionable. This is a placebo-controlled clinical trial of prazosin vs. the SSRI paroxetine for combat trauma-related nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) clinical severity in OIF/OEF returnees. Both neurobiologic considerations and our preliminary clinical treatment data provide support for the proposed trial. Preclinical and clinical studies suggest a role for increased central nervous system (CNS) adrenergic outflow and/or responsiveness in PTSD pathophysiology. Possible mechanisms include alpha-1 adrenergic receptor-mediated effects on sleep physiology, corticotropin releasing hormone secretion, and disruption of cognitive processing. Here we propose a double-blind, placebo-controlled parallel group 12 week clinical trial of prazosin vs. paroxetine to test the following hypotheses: Hypothesis 1. Prazosin will be more effective than paroxetine or placebo for reducing frequency and intensity of combat trauma-related nightmares (as measured by the "distressing dreams" item of the Clinician Administered PTSD Scale \[CAPS\]). Hypothesis 2. Prazosin will be more effective than paroxetine or placebo for improving sleep quality (as measured by the Pittsburgh Sleep Quality Index \[PSQI\]). Hypothesis 3. Prazosin will be more effective than paroxetine or placebo for improving overall clinical status (as measured by the Clinical Global Impression of Change \[CGIC\]). Hypothesis 4. Prazosin will be better tolerated than paroxetine as measured by days retained in the study and frequency of adverse events. Primary outcome measures will assess trauma-related nightmares, sleep disturbance and change in global clinical status: these will include the CAPS \[59\] Recurrent Distressing Dreams item, the PSQI (60) and the CGIC (58) score. Secondary outcome measures will include total CAPS score, the CAPS subscale scores (Reexperiencing/ Intrusions, Avoidance/Numbing, and Hyperarousal), the Nightmare Frequency Questionnaire (NFQ), Insomnia Severity Index, and measures of depressive signs and symptoms, quality of life, and number of study days completed.

Stress Disorders, Post-Traumatic Sleep Disorders

Prazosin Paroxetine Stress Disorders, Post-Traumatic Sleep Disorders

null

3

arm 1: Prazosin arm 2: Paroxetine arm 3: Placebo

[ 0, 1, 2 ]

3

[ 0, 0, 0 ]

intervention 1: taken by mouth, twice daily, titrated up to efficacy or a maximum of 5 mg at 10a and 25 mg at bedtime for duration of study intervention 2: 20 mg taken at 10a for duration of the study intervention 3: Placebo

intervention 1: prazosin intervention 2: paroxetine intervention 3: Placebo

2

0

NCT00202449

[ 3, 4 ]

16

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

false

Patients will receive budesonide or placebo for the treatment of active lymphocytic colitis. This study includes stool collections, blood draws, weekly questionnaires and a sigmoidoscopy. The study hypothesis is that budesonide will be safe and effective compared with placebo for the treatment of diarrhea in lymphocytic colitis.

Microscopic colitis is an increasingly diagnosed cause of chronic diarrhea, with two main subtypes: collagenous and lymphocytic colitis. Uncontrolled reports have suggested that various drugs can be beneficial in treating microscopic colitis, but few treatments have been evaluated in randomized controlled trials. Thus, treatment is guided mostly by anecdotal reports, case series, and physicians' experience. In our uncontrolled experience, corticosteroids are one of the most effective therapies for microscopic colitis, but are not typically used as a first line therapy because of toxicity. Budesonide has been reported to be of clinical benefit in small, uncontrolled series of patients with microscopic colitis, and recent controlled trials showed that it is superior to placebo in collagenous colitis. We propose a study of budesonide in patients with the lymphocytic type of microscopic colitis. Patients will have stool specimen and blood drawn at the start of the study. Patient will take either Budesonide or placebo for 8 weeks. At the end of treatment, patient will have stool collection and sigmoidoscopy.

Lymphocytic Colitis Diarrhea

Lymphocytic Colitis diarrhea budesonide

Prot_SAP_ICF_000.pdf: A Randomized, Double-Blind, Placebo- Controlled Trial of Budesonide For The Treatment Of Active Lymphocytic Colitis NCT00217022 May 17, 2017 A R a n d o mize d, D o u ble -Bli n d, Pl ace b o -C o ntr olle d Tri al of B u des o ni de F or T he Tre at me nt Of Acti ve L y m p h oc ytic C olitis Pri nci ple I n v esti gat or: D arrell S. Par di, M D C oi n vesti gat ors: Willia m J. Sa n d b or n. M D Lisa A. B oar d ma n, M D Peter W. Carr yer, M D J o nat ha n E. Clai n, M D La wre n ce J. E g a n, M D E d war d V. L oft us, M D Ke n net h W. Sc hr oe der, M D T h o mas C. S m yr k, M D Willia m J. Tre mai ne, M D Ala n R. Zi ns miester, P h D Patricia P. Ka m mer Di visi o n of Gastr oe nter ol o g y a n d He pat ol o g y, Ma y o Cli nic a n d F o u n dati o n, R oc hester, Mi n nes ota. 2 I. A bstr act: Micr osc o pic c olitis is a n i ncreasi n gl y dia g n ose d ca use of c hr o nic diarr hea, wit h t w o mai n s u bt y pes: c olla ge n o us a n d l y m p h oc ytic c olitis. U nc o ntr olle d re p orts h a ve s u g geste d t hat vari o us dr u gs ca n b e be n eficial i n treati n g micr os c o pic c olitis, b ut fe w treat me nts ha ve bee n e val uate d i n r a n d o mize d c o ntr olle d trials. T h us, treat me nt is g ui de d m ostl y b y a nec d otal re p orts, cas e seri es, a n d p h ysicia ns' e x perie n ce. I n o ur u nc o ntr olle d e x p erie nce, c ortic ost er oi ds are o ne of t he m ost eff ecti ve t hera pies f or micr osc o pic c olitis, b ut are n ot t y picall y use d as a first li ne t hera p y beca use of t o xicit y. B u des o ni de has bee n re p orte d t o be of cli nical be nefit i n s mall, u nc o ntr olle d series of patie nts wit h micr osc o pic c olitis, a n d rece nt c o ntr olle d trials s h o we d t hat it is s u peri or t o place b o i n c olla ge n o us c olitis. We pr o p ose a st u d y of b u des o ni de i n patie nts wit h t he l y m p h oc ytic t y pe of micr osc o pic c olitis. II. B ac k gr o u n d a n d Si g nific a nce: Micr osc o pic c olitis is a r elati vel y c o m m o n ca use of c hr o nic w ater y diarr hea. T he t w o mai n t y pes of micr osc o pic c olitis are l y m p h oc ytic a n d c olla ge n o us c olitis. N u mer o us t hera pies ha ve bee n descri be d f or t hese c o n diti o ns ( 1), b ut o nl y bis m ut h s u bsalic ylate ( 2) a n d b u des o ni de ( 3, 3a, 3 b) ha ve bee n st u die d i n ra n d o mize d c o ntr olle d trials. I n t he lar gest u nc o ntr olle d series of p atie nts wit h l y m p h oc ytic c olitis ( 4) a n d c olla ge n o us c olitis ( 5), c ortic oster oi ds ar e a m o n g t he m ost effecti ve t h era pies wit h res p o nse rates of 7 0 - 8 0 %. H o we ver, tra diti o nal c ortic oster oi ds ha ve si g nifica nt s h ort- a n d l o n g- ter m si de effects, ca usi n g s o me cli nicia ns t o a v oi d t heir use. B u des o ni de is a s y nt hetic c ortic oster oi d wit h hi g h p ote nc y b ut li mite d s yste mic bi oa vaila bilit y d ue t o hi g h first -pass he patic meta b olis m ( 6). T he c o ntr olle d ileal r elease ( CI R) f or m ulati o n of b u des o ni de a vaila ble i n t h e U S ( E nt oc ort 3 E C) is desi g ne d t o deli ver dr u g ma xi mall y t o t he distal ile u m a n d pr o xi mal c ol o n, c o m pare d t o t he B u de n ofal k f or m ul ati o n use d i n t he Baert st u d y ( 3), t hat is desi g ne d t o deli ver dr u g t o t he c ol o n ( 6). T h us, E nt oc ort E C is t he oreticall y less i deal f or a p a nc ol o ni c pr ocess li ke micr osc o pic c olitis. H o we ver, o nl y 5 2- 7 9 % of b u des o ni de is a bs or be d i n t he ile ocecal re gi o n, lea vi n g 2 1- 4 8 % of t he dr u g f or deli ver y t o t he c ol o n ( 6). F urt her m ore, se v eral case re p orts ha ve s h o w n efficac y of t he CI R f or m ulati o n i n c olla ge n o us a n d l y m p h oc ytic c olitis ( 5, 7- 9), i ncl u di n g pre d nis o ne-r efr act or y cases ( 8), a n d t w o ra n d o mize d trials ha v e s h o w n t he CI R f or m ulati o n t o be s u peri or t o place b o i n patie nts wit h c olla ge n o us c olitis ( 3a, 3 b). T heref ore, CI R b u des o ni de ma y als o pr o ve t o be a n effecti ve treat me nt f or l y m p h oc ytic c olitis. T he c o nce pt of "satisfact or y c o ntr ol" of diarr hea is si milar t o t he "a de q uate relief" e n d p oi nt de v el o pe d t o pr o vi de a mea ni n gf ul, patie nt-e val uat e d meas ure of i m pr o ve m e nt i n s u bjects wit h diarr hea- pre d o mi na nt I B S ( 1 2). I n a d diti o n, t he dail y n u m ber of st o ols will be use d as a q ua ntitati ve meas ure of efficac y. I n I B S, "a de q u ate relief" c orrelates wit h v ari o us " o bjecti ve" meas ures s uc h as pai n se verit y sc ores a n d fre q ue n c y a n d c o nsiste nc y of st o ols ( 1 2). T his c o nce pt is bei n g a d a pte d f or t he pres e nt st u d y t o a d d a s u bjecti ve c o m p o ne nt t o t he patie nt's e val uati o n, si nce diarr hea as a s y m pt o m is s u bjecti ve a n d si m pl y s h o wi n g a c ha n ge i n t he n u m ber of st o ols per da y ma y n ot reflect t he patie nt's e x perie nce. Alt h o u g h micr osc o pic c olitis ma y be c o nsi dere d u nc o m m o n b y s o me, it acc o u nts f or a p pr o xi matel y 1 0 % of c hr o nic diarr h ea. I n E ur o p ea n st u dies, its i nci de nce is a p pr o xi matel y 5. 7/ 1 0 0, 0 0 0 ( 1), a p pr o ac hi n g t hat of Cr o h n's disease ( 1 0) a n d ulcerati ve c olitis ( 1 1). T he 4 si g nifica nce of t h e pr o p ose d st u d y lies i n t he fact t hat t here are fe w c o ntr olle d trials t o g ui de t hera pe utic c h oices i n patie nts wit h l y m p hoc ytic c olitis. Fecal Lact oferri n A nal ysis: A variet y of st o ol mar kers ha ve b ee n assesse d as dia g n ostic tests t o disti n g uis h patie nts wit h diarr hea d ue t o i nfla m mat or y c o n diti o ns fr o m t h ose wit h n o ni nfla m mat or y ca uses. Lact oferri n is a gl yc o pr otei n c o ntai ne d i n ne utr o p hilic sec o n dar y gra n ules t hat is release d i n res p o nse t o ne utr o p hil acti vati o n. Of se veral pr otei ns releas e d b y acti vate d ne utr o p hils, lact oferri n was s h o w n t o be t he m ost sta ble i n feces, a n d its release was f o u n d t o be m ost efficie nt ( S ugi, et al. A m J Gastr o 1 9 9 6; 9 1: 9 2 1). Fecal lact oferri n is i ncrease d i n p atie nts wit h bacterial ca uses of diarr hea w hic h res ult i n i nfla m mati o n c o m pare d t o patie nts wit h diarr hea d u e t o n o ni nfla m mat or y bacteria, vir uses, or t h ose i n w hic h n o or ga nis m w as i de ntifie d ( Gree n b er g, et al. J I nfect Dis 2 0 0 2; 1 8 5: 9 4 4, McI v er, et al. Pat h ol o g y 2 0 0 1; 3 3: 3 5 3, C h oi. J Cli n Micr o bi ol 1 9 9 6; 3 4: 2 3 3 7). I n fact, s o me a ut h ors c o nsi der it as t he scree ni n g test of c h oice f or patie nts wit h ac ute diarr h ea t o deter mi ne w h o s h o ul d ha ve st o ol c ult ures perf or me d ( H uic h o Pe diat I nf ect Dis J 1 9 9 7; 1 6: 6 4 4). Fecal lact oferri n has bee n s h o w n t o be as usef ul as fecal occ ult bl o o d testi n g i n detecti n g vari o us c ol orectal diseases ( Sait o h I nter n Me d 2 0 0 0; 3 9: 7 7 8). Fecal lact of erri n has b ee n st u die d fairl y e xte nsi vel y i n i nfla m mat or y b o wel disease a n d has bee n s h o w n t o be a s e nsiti ve a n d s pecific m ar ker of acti ve I B D c o m p are d t o irrita ble b o wel s y n dr o me a n d h ealt h y c o ntr ols ( Ka ne, et al. Gastr oe nter ol o g y 2 0 0 1; 1 2 0: A 2 7 6, B u der us, et al. Gastr o e nter ol o g y 2 0 0 2; 1 2 2: A 2 1 9 # 1, Fi ne. A m J Gastr o 1 9 9 8; 9 3: 1 3 0 0). 5 I n p atie nts wit h I B D, t h e le vels of fecal lact oferri n c orrel ate wit h disease acti vit y ( B o o ne, et al. Gastr oe nt er ol o g y 2 0 0 0; 1 1 8: A 1 1 1 8, B u der us, et al. Gastr oe nt er ol o g y 2 0 0 2; 1 2 2: A 2 1 9 # 1), a n d i n i n di vi d ual patie nts, t he le vel of lact oferri n decreases w h e n re missi o n is i n d uce d ( B u der us, et al. Gastr oe nter ol o g y 2 0 0 2; 1 2 2: A 2 1 9 # 2). T here is o nl y o ne r e p ort i n t he literat ure w h ere fecal lact oferri n le vels were st u die d i n micr osc o pic c olitis ( Fi ne et al. A m J Gastr o 1 9 9 8; 9 3: 1 3 0 0). I n t his s mall st u d y, 8 % of patie nts wit h micr osc o pic c olitis ha d ele vate d fecal lact oferri n le vels. H L A Ass ociati o ns: O ne st u d y of H L A ha pl ot y pes s h o we d a n i ncreas e i n A 1 a n d D R W 5 3 i n l y m p h oc ytic c olitis a n d a decr eas e i n D Q 2 i n c olla ge n o us c olitis ( 1 3). H o we ver, t his sa me gr o u p later re p ort e d i ncreas e d A 1 a n d d ecrease d i n A 3 i n l y m p h oc ytic c olitis a n d n o H L A ass ociati o ns i n c oll a ge n o us c olitis ( 1 4). Fi n e a n d c ollea g ues s h o we d a n i ncrease i n D Q 2 a n d D Q 1, 3 i n l y m p h oc ytic c olitis a n d c olla g e n o us c olitis, si milar t o t he patter n see n i n celiac s pr u e ( 1 5). Ot h ers ha ve f o u n d n o H L A ass ociati o ns ( 1 6). A b n or mal H L A D R e x pressi o n o n c ol o nic e pit helial cells has bee n d es cri be d, s u g gesti n g t hat M H C- restricte d i m m u ne acti vati o n c o ul d be i n v ol ve d i n t he pat h o g e nesis of micr osc o pic c olitis ( 1 7, 1 8). Gi ve n t he discre p a nt fi n di n gs, h o we ver, it is diffic ult t o dra w c o ncl usi o ns a b o ut H L A ass ociati o ns i n micr osc o pic c olitis. III. H y p ot heses: 1) B u des o ni de will be safe a n d eff ecti ve c o m pare d wit h place b o f or t h e treat me nt of diarr hea i n l y m p h oc ytic c olitis. 6 2) Fecal lact of erri n le v els will c orrelate wit h s y m pt o ms a n d hist ol o gic disease acti vit y i n patie nts wit h l y m p h oc ytic c olitis. I V. S pecific Ai ms: 1) T o c o m par e efficac y of b u des o ni de a n d place b o i n l y m p h oc ytic c olitis i n pr o vi di n g relief of diarr hea ( pri mar y e n d p oi nt) as well as i n i m pr o vi n g fre q ue n c y, c o nsiste nc y, a n d ur ge nc y of diarr hea a n d de gree of i nfla m mati o n o n c ol o n bi o psies (sec o n dar y e n d p oi nts). 2) T o c o m par e t he saf et y a n d t olera bilit y of b u des o ni de c o m pare d t o place b o i n patie nts wit h l y m p h oc ytic c olitis (sec o n dar y e n d p oi nt). 3) T o assess t he c orrel ati o n bet wee n fecal lact oferri n c o nce ntrati o ns a n d s y m pt o ms a n d de gree of i nfla m mati o n o n m uc osal bi o psies i n patie nts wit h l y m p h oc ytic c oliti s. 3) T o c har acteri ze H L A t y pi n g i n patie nts wit h l y m p h oc ytic c olitis. V. Preli mi n ar y st u dies: T he t hera p e utic p ote ntial of b u des o ni de f or t he treat me nt of l y m p h oc ytic c olitis is disc usse d a b o ve. Fr o m 1 9 9 7- 1 9 9 9, i ncl usi ve, a p pr o xi matel y 2 0 0 patie nts wit h l y m p h oc ytic c olitis a n d 2 0 0 wit h c olla ge n o us c olitis were e val uate d at Ma y o, or 1 3 3 patie nts per year wit h eit her c o n diti o n. We h a ve pre vi o usl y re p orte d o ur e x peri e nce wit h t hera p y i n patie nts wit h l y m p h oc ytic c olitis ( 4). I n a d diti o n, o ur gr o u p has e xte nsi ve e x perie n ce wit h cli nical trials i n patie nts wit h i nfla m mat or y b o wel disease. VI. Rese arc h Desi g n a n d Met h o ds: A. St u d y desi g n: We pr o p ose a pr os pecti ve, ra n d o mize d, d o u ble bli n d, place b o- c o ntr olle d trial of b u des o ni de f or t he treat me nt of l y m p h oc ytic c olitis. 7 B. Recr uit me nt: P ote ntiall y eli gi ble s u bjects will be i de ntifie d at Ma y o R oc hester i n se veral w a ys. First, r ece ntl y dia g n ose d cases will be i de ntifie d b y dail y re vie w of t he dia g n oses ma de i n t he D e part me nt of Pat h ol o g y. Sec o n d, t h e GI a p p oi nt me nt office at t he Ma y o Cli nic will i de ntif y s u bjects referre d wit h a dia g n osis of l y m p h oc ytic c olitis. T hir d, patie nts w h o ha ve bee n dia g n ose d wit hi n t he last t hree years at M a y o will be c o ntact e d b y letter ( A p pe n di x 1) a n d i nf or me d of t he st u d y. As n ote d a b o ve, a p pr o xi matel y 1 3 3 patie nts wit h micr osc o pic c olitis are see n eac h year at M a y o, a n d a p pr o xi matel y 4 0 0 were s ee n i n t he last t hree years, gi vi n g a p o ol of o ver 5 0 0 s u bjects wit h micr osc o pic c olitis. A p pr o xi matel y half of t hese will ha ve l y m p h oc ytic c olitis, lea vi n g ~ 2 5 0 p ote ntial s u bjects f or e nr oll me nt. We will recr uit s u bjects u ntil we e nr oll 3 0 wit h l y m p h oc ytic c olitis. C. I ncl usi o n Criteria: 1. A ge ≥ 1 8 years of a g e. 2. Diarr hea, defi n e d as a mi ni m u m of 3 b o wel m o ve me nts per da y a n d greater t ha n “ mil d” (see bel o w), c urre ntl y o n n o treat me nt or acti ve des pite treat me nt. 3. L y m p h oc ytic c olitis c o nfir me d hist ol o gicall y b y t he st u d y pat h ol o gist ( T C S) o n left si de d c ol o n bi o psies. If bi o psies are n ot a vaila ble wit hi n o ne year of st u d y e ntr y, re peat fle xi ble si g m oi d osc o p y wit h left si de d bi o psies ( 2 si g m oi d, 2 desce n di n g) will be p erf or me d. D. E xcl usi o n Criteria: 1. Pre vi o us u ns uccessf ul treat me nt wit h c ortic oster oi ds or i m m u n os u p pressi ve dr u gs. 2. Hist or y of se ver e c orti c oster oi d si de effects. 8 3. C ortic oster oi d, ticl o pi di ne, or fl uta mi de use wit hi n t he pre vi o us 4 wee ks. 4. A nti bi otic, mesala mi ne or bis m ut h s u bsalic ylate use wit hi n t w o wee ks. 5. C urre nt use of a ntic h oli ner gics, c h olest yra mi ne, narc otics, ket o c o naz ol e, itrac o naz ol e, rit o na vir, i n di na vir, sa q ui na vir, er yt hr o m yci n, or gra pefr uit j uice. 6. K n o w n acti ve me di cal c o n diti o ns, i ncl u di n g ca ncer, i nfecti o n, u nc o ntr olle d h y perte nsi o n or dia betes, oste o p or osis, pe ptic ulcer diseas e, gla uc o ma, cataracts, li ver cirr h osis or hist or y of t u berc ul osis. 7. Ot her diarr heal c o n diti o ns (s pr ue, i nfecti o n, h y pert h yr oi dis m, lact ose i nt olera nce). 8. Pre g na nt or n ursi n g f e males. 9. Patie nts wit h o ut a tele p h o ne or u na ble t o c o m m u nicate i n E n glis h o ver t he tele p h o ne, or u na ble or u n willi n g t o gi ve c o nse nt. 1 0. K n o w n h y perse nsiti vit y t o or i nt olera nce of b u des o ni de. E. Met h o ds: Patie nts wit h bi o ps y- pr o ve n l y m p h oc ytic c olitis will c o m plete a s y m pt o m q uesti o n naire ( A p p e n di x 2). T here will be a o ne- wee k peri o d of o bser v ati o n pri or t o st u d y e ntr y t o i ns ure s uffici e ntl y si g nifica nt diarr hea. All dr u gs use d t o treat c olitis will be disc o nti n ue d f or t he a p pr o priate ti me peri o d (s ee e xcl usi o n criteria a b o v e) pri or t o t he start of t his o bser vati o n peri o d. L o pera mi de will be st o p pe d at least t w o da ys pri or t o t he o bser vati o n peri o d. D uri n g t he o ne- w ee k o bs er vati o n peri o d, s u bjects will ma ke a dail y rec or d of t he n u m ber of b o wel m o ve m e nts a n d s u bjecti vel y sc ore t heir diarr hea as " n o ne" ( 0), " mil d" ( 1), " m o derate" ( 2), or "se ver e" ( 3). T o q ualif y f or t he st u d y, t he mea n n u m ber of dail y b o wel m o ve me nts m ust be > 4, a n d t he mea n diarr hea sc ore m ust be > 1. 9 After e ns uri n g s ufficie ntl y se vere di arr h ea f or partici pati o n, a st o ol sa m ple will be c ollecte d f or meas ur e me nt of t he fecal lact oferri n le vel (see b el o w) . O n ce d uri n g t he st u d y bl o o d will be dra w n f or H L A t y pi n g (see b el o w). W o me n of c hil d beari n g p ote ntial will ha ve a ser u m pre g n a nc y test p erf or me d. T hirt y s u bjects wit h l y m p h oc ytic c olitis will be ra n d o mize d e q u all y ( 1: 1) b y t he use of ra n d o m- or dere d, seale d, o pa q u e e n vel o pes t o b u des o ni de 9 m g/ d or a place b o. T he st u d y dr u g will be ta ke n dail y f or 8 wee ks. T he st u d y assista nt will m o nit or s u bjects b y tele p h o ne wee kl y f or c o m plia nce, efficac y, a n d si de eff ects. L o pera mi de will be all o we d as "res c ue" t h era p y f or > 7 b o wel m o ve me nts per da y, a n d t he n u m ber of ta blets ta k e n will be rec or de d a n d use d as a sec o n dar y o utc o me meas ur e. Fecal lact of erri n a n al ysis: We will use t he I B D -S C A N q ua ntitati ve lact oferri n E LI S A test pr o vi de d b y Tec h L a b, Blac ks b ur g, Vir gi nia. A sta n dar d c ur ve is ge n erate d usi n g p urifie d h u ma n lact oferri n. Patie nt fecal s peci me ns are dil ute d seriall y 1: 1 0, a n d t h e dil uti o n gi vi n g a n o ptical de nsit y o n t he li near part of t he c ur ve is us e d t o deter mi ne lact oferri n c o nce ntrati o n. F. Safet y M o nit ori n g: I n pri or st u dies, b u des o ni de treat me nt f or 8 w ee ks h as bee n e xtre mel y saf e, wit h a n a d verse e v e nt pr ofile si milar t o place b o. T h us, we are pr o p osi n g t o d o t his st u d y wit h o ut a Dr u g Safet y M o nit ori n g B oar d. I n a d diti o n, we d o n ot pla n o n ha vi n g st o p pi n g r ules i n place f or t o xicit y. We will m o nit or f or a n y a d vers e e ve nts i n st u d y patie nts, a n d we will m o nit or f or l ac k of efficac y. As me nti o ne d a b o ve, l o pera mi de will be all o we d f or t h ose patie nts w h o ha ve > 7 b o wel m o ve me nts per da y. If t he di arr h ea d oes n ot res p o n d t o t his 1 0 s y m pt o matic treat me nt, t he patie nt will be wit h dra w n fr o m t he st u d y, c o u nt e d as a treat me nt fail ure, a n d pr o vi de d o pe n-la bel treat me nt at t he directi o n of o ne of t h e st u d y p h ysicia ns or t heir re g ular p h ysicia n. G. F oll o w- u p a n d E n d p oi nt Ascertai n me nt: Eac h p atie nt will rec or d t he c o nsiste nc y a n d fre q ue n c y of st o ols, ur ge nc y, a b d o mi nal disc o mf ort, a n d a n y ot her s y m pt o ms dail y ( A p pe n di x 3). At eac h wee kl y tel e p h o ne f oll o w- u p, t he pri m ar y e n d p oi nt of "satisfact or y c o ntr ol of diarr hea" will be assesse d. After 8 w ee ks of treat me nt, t he st u d y dr u g will be st o p pe d a n d a ret ur n offi ce visit will occ ur. Re peat fle xi ble si g m oi d osc o p y wit h left si de d c ol o n bi o psies ( 2 si g m oi d, 2 desce n di n g) will be o btai ne d wit hi n 7 da ys. A bli n de d pat h ol o gist ( T C S) will c o m pare t hes e bi o psies t o pretreat me nt bi o psies acc or di n g t o t he para meters liste d i n A p pe n di x 4. Res p o n ders will be f oll o we d wee kl y f or a n ot her f o ur w ee ks f or rec urre n ce, defi n e d as > 4 st o ols per da y or a st o ol c o nsiste nc y sc ore of 4 or 5 ( A p pe n di x 3). H. A ntici pate d Res ults: We a ntici pate t h at b u des o ni de will be s u peri or t o place b o wit h o ut i ncrease d si de effects. I. Data A n al ysis: T he pri mar y a nal ysis will c o m pare t he pr o p orti o n of pati e nts i n eac h treat me nt gr o u p wit h satisfact or y c o ntr ol of diarr h ea d uri n g at least t hree of t he last f o ur wee ks of t he st u d y ( pri mar y e n d p oi nt). A t w o- sa m ple z-s c ore test f or pr o p orti o ns will be use d t o test w het her t he "r elief r ates" are diff er e nt bet wee n t he gr o u ps. Sec o n dar y a nal yses will c o m pare t he t w o treat me nt gr o u ps o n: 1) res p o nse, d efi ne d as 5 0 % decrease i n n u m ber of st o ols per da y ( mea n pr e-treat me nt wee k vs. mea n d uri n g wee k 8 of treat me nt); 2) t h e pr o p orti o n ( per patie nt) of t otal st u d y da ys wit h o ut diarr hea; 3) t h e pr o p orti o ns of patie n ts e x perie n ci n g "i m pr o ve me nt" 1 1 i n st o ol c o nsiste nc y, ur ge nc y a n d a b d o mi nal pai n b y at least o ne p oi nt ( o n t he scale us e d i n A p pe n di x 3). T hes e res ults will be c o m pare d usi n g a t w o-sa m ple test f or pr o p orti o ns. Fi nall y, hist ol o gic i m pr o ve me nt c o m pare d t o ba seli ne bi o psies will be assesse d ( A p pe n di x 4) as well as si de effects a n d ti me (i n da ys) t o rec urre n ce of diarr hea after disc o nti n uati o n of st u d y dr u g. Alter nati ve a n al yses f or t he pri mar y a n d s ec o n dar y e n d p oi nts will be base d o n ge neralize d re gressi o n m o dels i nc or p orati n g p ote ntiall y i m p orta nt c o variates (e. g. a g e, ge n der, s u bt y pe of c olitis) al o n g wit h treat me nt gr o u p as pre dict ors of res p o nse. F or e x a m ple, a l o gistic re gressi o n a nal ysis of satisfact or y c o ntr ol of diarr hea ( Y es, N o) as t he bi nar y d e pe n de nt varia ble will be e xa mi ne d, a n d t he o d ds r ati o ( 9 5 % CI) f or relief (treate d: n ot treate d) esti mate d usi n g t he re gressi o n c o effi cie nt fr o m t he m o del. A d diti o nal s u m maries of patie nt c h aract eristics, hist ol o g y, a n d si de effects will be ge nerat e d f or eac h treat me nt gr o u p. Fecal lact of erri n le v els will be c o m pare d wit h t he de gree of diarr hea a n d hist ol o g y ( A p pe n di x 4) at baseli ne a n d at wee k 8. H L A t y pe distri b uti o n will be descri be d. Data will be a n al yze d usi n g a n "i nte nti o n- t o-treat" met h o d ol o g y, a n d dr o p- o uts will be c o u nte d as fail ures. J. Sa m ple Size Assess me nt: Base d o n u nc o ntr olle d data, t he res p o nse t o ster oi ds i n micr osc o pic c olitis is a p pr o xi matel y 7 0- 8 0 % ( 4, 5). T he a vera ge res p o nse t o b u des o ni de i n t he ra n d o mize d tri als i n c olla ge n o us c olitis was 7 7 %, w hile t he b est res p o nse t o place b o was 2 1 %. At a n al p ha of 0. 0 5 a n d usi n g a t w o- 1 2 si de d test, 1 5 patie nts will be nee de d i n t he treat m e nt gr o u p a n d 1 5 i n t he place b o gr o u p t o ha v e 8 0 % p o wer t o det ect a si milar differe nce i n o ur st u d y of patie nts wi t h l y m p h oc ytic c olitis. T h us, t he t otal sa m ple size will be 3 0 s u bjects. Ti m et a ble: If t he n u m ber of s u bjects see n at Ma y o re mai ns sta ble, we w o ul d e x pect t o see 6 5 patie nts eac h year wit h l y m p h oc ytic c olitis. We ha ve n o data o n h o w ma n y w o ul d satisf y t he i ncl usi o n a n d e xcl usi o n criteria. We will atte m pt t o i ncrease e nr oll me nt b y c o ntacti n g patie nts see n i n t he last t hree years at Ma y o, i nf or mi n g t he m b y mail of t he st u d y a n d i n viti n g t heir partici pati o n ( A p pe n di x 1). We a ntici pate e nr olli n g 3- 5 s u bjects per m o nt h, or 3 0 s u bjects i n 6- 9 m o nt hs, a n d c o m pleti n g t he st u d y wit hi n 1 2 m o nt hs. VII. H u m a n S u bjects : 1. P o p ulati o n: A d ults ≥ 1 8 years ol d wit h acti ve l y m p h oc ytic c olitis. 2. Researc h m aterials: St u d y data will i ncl u de de m o gra p hics, s y m pt o ms, c ol o n bi o psies, st o ol f or lact oferri n a nal ysis a n d bl o o d f or H L A t y pi n g. 3. Recr uit me nt: Patie nts will be i de ntifie d at Ma y o t hr o u g h t he De p art me nt of Pat h ol o g y a n d t he Di visi o n of Gastr oe nt er ol o g y a n d H e pat ol o g y. I n a d diti o n, patie nts see n wit hi n t he past t hree years at Ma y o will be c o ntacte d b y mail ( A p pe n di x 1). 4. P ote ntial ris k/ pr otecti o n: B u des o ni de has a ver y fa v ora ble s afet y pr ofile, wit h si de effects c o m para ble t o place b o ( p ac ka g e i nsert). It is F D A a p pr o ve d f or use i n Cr o h n’s disease. Fle xi ble si g m oi d osc o p y wit h m uc osal bi o ps y is a ver y safe pr oce d ure, wit h < 1 % ris k of seri o us a d vers e e v e nts. T he mai n ris ks will be disc o mf ort relat e d t o t he use of e ne m as a n d 1 3 of t he pr oce d ure itself. Alt h o u g h b u des o ni de was s u peri or t o place b o i n pri or st u dies i n c olla ge n o us c olitis ( 3, 3a, 3 b), it has n ot bee n st u die d i n l y m p h oc ytic c olitis. I n a d diti o n, a si g nifica nt rate of s p o nta ne o us re missi o n has bee n re p orte d i n micr os c o pic c olitis ( 1). F urt her m ore, w e will all o w t he use of l o pera mi de f or brea kt hr o u g h diarr h ea. T h us, a place b o c o ntr ol ar m is j ustifie d a n d et hical. 5. Be nefits: T he a vera ge b e nefit of b u des o ni de i n c olla ge n o us c o litis was 7 7 % i n c o ntr olle d st u dies ( 3, 3a, 3 b). Si milar be nefit is e x pecte d i n t h ose wit h l y m p h oc ytic c olitis. N o be nefit is e x pecte d f or t h ose s u bjects ra n d o mize d t o place b o. Re m u nerati o n will n ot be offer e d. C osts relate d s olel y t o t he st u d y (st u d y me dicati o n, f oll o w u p si g m oi d osc o p y a n d bi o ps y) will be pai d f or b y t he st u d y b u d get. VI. Ge n der/ Mi n orit y Mi x: I n m ost r e p orts, c olla ge n o us c olitis occ urs mai nl y i n fe males w hereas l y m p h oc ytic c olitis has a m ore e v e n ge n der distri b uti o n. T here are n o dat a o n raci al distri b uti o n, b ut m ost re p orte d cases are Ca u casia ns. We will e nr oll s u bjects of eit her ge n der a n d a n y race. 1 4 A p pe n di x 1. Recr uit me nt Letter Dear , M y c ollea g ues a n d I ar e perf or mi n g a researc h st u d y of a ne w m e dicati o n f or t he treat me nt of l y m p h oc ytic c olitis. Acc or di n g t o o ur rec or ds, y o u ha ve b ee n dia g n ose d wit h t his c o n diti o n i n t he past. If y o ur diarr hea is still si g nifica nt, y o u mi g ht q ualif y t o e nr oll i n t his st u d y. If y o u are i ntereste d or h a ve a n y q uesti o ns, please c o ntact (st u d y assista nt) at . Y o ur decisi o n t o ta ke p art i n t his st u d y is e ntirel y v ol u ntar y. C urre nt or f ut ure me dical care at t he Ma y o Cli nic will n ot be affecte d b y y o ur decisi o n. Si ncerel y, Darr ell S. Par di, M D 1 5 A p pe n di x 2. I nitial s y m pt o m q uesti o n naire. Na me _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ M C N _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 1) H o w w o ul d y o u rat e y o ur diarr hea? 0 1 2 3 N o ne Mil d M o derate Se vere 2) W hat is t he c o nsiste nc y of y o ur st o ols us uall y? 1 2 3 4 5 Ver y har d Har d F or me d L o ose Water y 3) H o w se vere is y o ur a b d o mi nal pai n us uall y? 0 1 2 3 N o ne Mil d M o derate Se vere 4) I n t he last year, ha v e y o u ha d a b d o mi nal pai n f or at least 1 2 wee ks? Y es / N o 5) Is t he pai n r elie ve d b y a b o wel m o ve me nt? Yes / N o 6) Is t he pai n ass o ciate d wit h y o ur diarr hea? Y es / N o 7) Is t he pai n ass o ciate d wit h a c ha n ge i n st o ol f or m (a p peara nce)? Yes / N o 8) Are y o ur b o wel m o ve me nts us uall y ass ociate d wit h ur ge nc y? Yes / N o 9) H o w ma n y b o w el m o ve me nts d o y o u ha ve o n a us ual da y? _ _ _ _ _ 1 0) Is y o ur diarr hea c o nsta nt or i nter mitte nt? 1 1) Ha ve y o u l ost a n y w ei g ht? Yes / N o If y es, h o w m uc h? _ _ _ _ _ _ p o u n ds 1 2) D o y o u use as piri n or ot her art hritis/ pai n me dicati o ns at least t hree da ys per wee k? 1 3) If yes, w hi c h dr u g a n d w hat d ose? _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 1 4) D o y o u s m o ke? Y es / N o If Yes, h o w m u c h per da y? _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 1 5) If n o, di d y o u s m o ke i n t he past? Yes/ N o If Yes, h o w m uc h per da y? _ _ _ _ _ _ _ _ _ _ _ 1 6 A p pe n di x 3. Dail y S y m pt o m Q uesti o n naire T o da y's Date _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 1) H o w w o ul d y o u rat e y o ur diarr hea i n t he last 2 4 h o urs? 0 1 2 3 N o ne Mil d M o derate Se vere 2) W hat was t h e c o nsiste nc y of y o ur st o ols i n t he last 2 4 h o urs? 1 2 3 4 5 Ver y har d Har d F or me d L o ose Water y 3) H o w se vere w as y o ur a b d o mi nal pai n i n t he last 2 4 h o urs? 0 1 2 3 4 N o ne Mil d M o derate I nte ns e Se vere 4) Wer e y o ur b o w el m o ve me nts yester da y ass ociate d wit h ur ge nc y? Yes / N o 5) H o w ma n y b o w el m o ve me nts di d y o u ha ve yest er da y? _ _ _ _ _ _ _ _ _ _ _ 6) H o w ma n y l o per a mi de/I m o di u m di d y o u use y ester da y ? _ _ _ _ _ _ _ _ _ _ _ Wee kl y St u d y c o or di nat or i nter vie w q uesti o n naire: "I n t he p ast se ve n d a ys, ha ve y o u ha d s atisfact or y c o ntr ol of y o ur diarr hea?" "I n t he p ast se ve n d a ys, ha ve y o u ha d s atisfact or y c o ntr ol of y o ur a b d o mi nal pai n?" " Ha ve y o u ha d a n y si de effects fr o m t he st u d y me dicati o n?" " Ha ve y o u ha d a n y ne w s y m pt o ms?" " D o y o u ha ve a n y q u esti o ns?" A p pe n di x 4. Hist o pat h ol o g y Sc ori n g S yste m I T E M/ S C O R E 0 1 2 _ _ _ _ _ 3 _ _ _ _ _ _ _ _ _ E pit helial c ha n ges N o ne Mil d M o derate Se vere La mi na pr o pria cell ularit y N or mal Mil dl y i ncrease d M o deratel y i ncreas e d De nsel y i ncrease d I ntr ae pit helial l y m p h oc yt es N or mal Mil dl y i ncrease d M o deratel y i ncr eas e d Se verel y i ncrease d Ma xi m u m sc ore = 9, mi ni m u m = 0 Refere nces: 1. Par di D S, S m yr k T C, Tre mai ne WJ, Sa n d b or n WJ. Micr osc o pic c olitis: A re vie w. A m J Gastr oe nter ol 2 0 0 2; 9 7: 7 9 4- 8 0 2. 2. Fi ne K, O g u nji F, Lee E, Laf o n G, T a nzi M. Ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d trial of bis m ut h s u bsalic ylate f or micr os c o pic c olitis. Gastr oe nter ol o g y 1 9 9 9; 1 1 6: A 8 8 0. 3. Baert F, Sc h mit A, D' Hae ns G, et al. B u des o ni de i n c olla ge n o us c olitis: a d o u ble- bli n d place b o -c o ntr olle d trial wit h hist ol o gic f oll o w - u p. Gastr oe nter ol o g y 2 0 0 2; 1 2 2: 2 0- 2 5. 3a. B o n der u p O K, H a nse n J B, Bir ket- S mit h L, Vester gaar d V, Te gl bjaer g P S, Falli n g b or g J. B u des o ni de treat me nt of c olla ge n o us c olitis: a ra n d o mize d, d o u ble bli n d, place b o c o ntr olle d trial wit h m or p h o metric a nal ysis. G ut 2 0 0 3; 5 2: 2 4 8- 5 1. 3 b. Mie hl ke S, He y mer P, Bet h ke B, et al. B u des o ni de treat me nt f or c olla g e n o us c olitis: a ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, m ultice nter trial. Gastr o e nter ol o g y 2 0 0 2; 1 2 3: 9 7 8- 8 4. 4. Par di D S, Ra m nat h V R, L oft us E V Jr, Tre mai n e WJ, Sa n d b or n WJ. L y m p h oc ytic C olitis: Cli nical Feat ures, Treat me nt, a n d O utc o m es. Ma n uscri pt s u b mitte d. 5. B o hr J, T ys k C, Eri kss o n S, et al. C olla ge n o us c olitis: a retr os pecti ve st u d y of cli nical prese ntati o n a n d tr eat me nt i n 1 6 3 patie nts. G ut 1 9 9 6; 3 9: 8 4 6- 5 1. 6. Gree n b er g G R. Or al b u des o ni de. Cli n Pers pect Gastr oe nter ol 2 0 0 2: 9- 1 2. 7. Delari ve J, Sara ga E, D orta G, Bl u m A. B u des o ni de i n t he treat me nt of c olla ge n o us c olitis. Di gesti o n 1 9 9 8; 5 9: 3 6 4- 6. 8. La n yi B, Dries V, Die nes H P, Kr uis W. T hera p y of pre d nis o ne-refract or y c olla ge n o us c olitis wit h b u des o ni de. I nt J C ol orect Dis 1 9 9 9; 1 4: 5 8- 6 1. 1 9 9. Va n G oss u m A, Sc h mit A, Pe n y M- O. Oral b u d es o ni de f or l y m p h oc ytic c olitis. A m J Gastr oe nter ol 1 9 9 8; 9 3: 2 7 0. 1 0. L oft us E V Jr, Sil verstei n M D, Sa n d b or n WJ, Tre mai ne WJ, Har mse n W S, Zi ns meister A R. Cr o h n's disease i n Ol mste d C o u nt y, Mi n nes ota, 1 9 4 0- 1 9 9 3: I nci de n ce, pre val e nce, a n d s ur vi val. Gastr o e nter ol o g y 1 9 9 8; 1 1 4: 1 1 6 1- 8. 1 1. L oft us E V Jr, Sil verstei n M D, Sa n d b or n WJ, Tre mai ne WJ, Har mse n W S, Zi ns meister A R. Ulcerati ve c olitis i n Ol mste d C o u nt y, Mi n nes ota, 1 9 7 0- 1 9 9 3: I nci de n ce, pre v ale nce a n d s ur vi val. G ut 2 0 0 0; 4 6: 3 3 6- 4 3. 1 2. Ca milleri M, N ort hc utt A R, K o n g S, D u kes G E, Mc S orle y D, Ma n gel A W. Efficac y a n d safet y of al osetr o n i n w o me n wit h irrita ble b o wel s y n dr o me: a ra n d o mise d, place b o- c o ntr olle d trial. La ncet 2 0 0 0; 3 5 5: 1 0 3 5- 4 0. 1 3. Giar diell o F M, Laze n b y AJ, Ba yless T M, et al. L y m p h oc ytic ( micr osc o pic) c olitis. Cli nic o pat h ol o gic st u d y of 1 8 patie nts a n d c o m paris o n t o c olla ge n o us c olitis. Di g Dis Sci 1 9 8 9; 3 4: 1 7 3 0- 8. 1 4. Giar diell o F M, Laze n b y AJ, Yar dle y J H, et al. I n crease d H L A A 1 a n d di mi nis he d H L A A 3 i n l y m p h oc ytic c olitis c o m pare d t o c o ntr ols a n d patie nts wit h c olla ge n o us c olitis. Di g Dis Sci 1 9 9 2; 3 7: 4 9 6- 9. 1 5. Fi ne K D, D o K , Sc h ulte K, et al. Hi g h pre v ale nce of celiac s pr u e-li ke H L A-D Q g e nes a n d e nter o p at h y i n patie nts wit h t he micr osc o pic c olitis s y n dr o me. A m J Gastr oe nter ol 2 0 0 0; 9 5: 1 9 7 4- 8 2. 1 6. S yl westr o wicz T, K ell y J K, H wa n g, W S, et al. C olla ge n o us c olitis a n d micr osc o pic c olitis: t he water y diarr h ea -c olitis s y n dr o me. A m J Gastr oe nter ol 1 9 8 9; 8 4: 7 6 3- 8. 2 0 1 7. M os nier J F, Lar v ol L, Bar ge J, et al. L y m p h o c ytic a n d c olla ge n o us c olitis: a n i m m u n o hist oc he mical st u d y. A m J Gastr oe nter ol 1 9 9 6; 9 1: 7 0 9- 1 3. 1 8. Bea u gerie L, L u b oi ns ki J, Br o usse N, et al. Dr u g i n d uce d l y m p h oc ytic c olitis. G ut 1 9 9 4; 3 5: 4 2 6- 8. 2 1 TI T L E: A R a n d o mize d Pl ace b o C o ntr olle d Tri al of B u des o ni de i n Ly m p h ocytic C olitis I N V E S TI G A T O R: Dr. D. Par di a n d C ollea g ues A P P R O V E D B Y I N S TI T U TI O N A L R E VI E W B O A R D: T his is a n i m p ort a nt f or m. Ple ase re a d it c aref ull y. It tells y o u w h at y o u nee d t o k n o w a b o ut t his st u d y. If y o u a gree t o t a ke p art i n t his rese arc h st u d y, y o u nee d t o si g n t his f or m. Y o ur si g n at ure me a ns t h at y o u h a ve bee n t ol d a b o ut t he st u d y a n d w h at t he ris ks are. Y o ur si g n at ure o n t his f or m als o me a ns t h at y o u w a nt t o t a ke p art i n t his st u d y. W h y is t his st u d y bei n g d o ne ? T his st u d y is bei n g d o n e t o fi n d o ut w hat effects ( g o o d a n d ba d) b u des o ni de has o n y o u a n d o n t he diarr hea a n d ot her s y m pt o ms y o u ha ve fr o m y o ur l y m p h oc ytic c olitis (als o k n o w n as micr osc o pic c olitis). B u des o ni de is a me dicati o n t hat decreases i nfla m mati o n a n d has b ee n effecti v e i n treati n g ot her ca us es of diarr he a. It has bee n a p pr o ve d b y t he F D A, b ut has n ot bee n a p pr o v e d f or use i n l y m p h oc ytic c olitis. H o w m a n y pe o ple will t a ke p art i n t he st u d y ? T he pla n is t o ha ve 3 0 pe o ple ta ke part i n t his st u d y. All will be e nr olle d at Ma y o. W h at will h a p p e n i n t he st u d y ? Wit hi n t w o wee ks pri or t o starti n g t he st u d y me dicati o n, y o u will u n der g o a p h ysical e xa mi nati o n, a re vie w of y o ur me dic al hist or y, a n d scree ni n g bl o o d a n d st o ol tests if necessar y as part of a r e g ular cli nical e val uati o n. I n a d diti o n, c ol o n osc o p y or si g m oi d osc o p y (s c o pe i nt o t h e c ol o n) wit h bi o psies ma y be ta ke n if necessar y. If t hese tests i n dicate t hat l y m p h oc ytic c olitis is t he o nl y c a use f or y o ur diarr hea, y o u will b e as ke d t o fill o ut a si m ple, o ne pa ge f or m descri bi n g y o ur diarr hea a n d ot her s y m pt o ms. Y o u will als o b e as ke d t o st o p y o ur di arr hea me dicati o ns a n d f oll o w y o ur diarr h ea a n d ot her s y m pt o ms f or o n e we e k. At t hat p oi nt, it will be deci de d if y o u q u alif y f or t he st u d y. If y o u q ualif y f or t h e st u d y, y o u will s u b mit a st o ol sa m ple a n d h a ve a s mall a m o u nt of bl o o d dra w n. If y o u are a fe male a ble t o ha ve c hil dre n, s o me of t he bl o o d will be use d t o b e s ure y o u are n ot pr e g na nt. I n a d diti o n, if y o u ha ve n ot ha d bi o psies fr o m y o ur c ol o n i n m ore t ha n o n e ye ar as part of y o ur re g ul ar me dical care, y o u will ha ve a re peat si g m oi d osc o p y a n d bi o psies as part of t h e st u d y. 2 2 T he n, if y o u are n ot pre g na nt, y o u will be p ut i n o ne of t w o gr o u ps b y c ha nce (as i n t he fli p of a c oi n). O ne gr o u p will recei ve b u d es o ni de i n t he f or m of 3 milli gra m ta blets. T h e ot her gr o u p will recei v e a pl ac e b o (s u g ar) t a blet. S u bje cts i n eac h gr o u p will ta ke t hre e ta blets per da y f or ei g ht wee ks. T he 9 milli gra m d ose of b u des o ni de will be use d i n t his st u d y as it has bee n f o u n d t o be effe cti ve i n treati n g ot her t y pes of diarr h ea. F or t he ei g ht wee k d ur ati o n of t he st u d y, y o u will be as ke d t o kee p a si m ple dail y rec or d of y o ur diarr h ea a n d ot her s y m pt o ms. T he st u d y assista nt will call y o u o n t he tele p h o ne o nce p er wee k t o see h o w y o u ar e d oi n g. At t he e n d of ei g ht wee ks, t he st u d y me dicati o n will be st o p pe d. Y o u will s u b mit a sec o n d st o ol sa m ple. A re peat si g m oi d osc o p y (sc o pe i nt o t he l o wer c ol o n) wit h bi o psies will be perf or me d at Ma y o wit hi n se ve n d a ys. T his pr oce d ure is part of t he st u d y a n d t h eref ore will n ot be bille d t o y o u or y o ur i ns ura nce c o m pa n y. If y o ur s y m pt o ms h a ve i m pr o ve d o n treat me nt, we will f oll o w y o u o ver t he ne xt f o ur wee ks t o see if y o ur s y m pt o ms ret ur n after t he me dic ati o n is st o p pe d. D uri n g t he st u d y, y o u s h o ul d n ot use a n y ot her me dicati o ns f or diarr h ea e xce pt t h ose y o u ha ve disc uss e d wit h y o ur d oct or, i n cl u di n g o ver-t he-c o u nt er ( n o n- prescri pti o n) me dicati o ns. Y o u will be a ble t o use I m o di u m (l o p era mi de) t o c o ntr ol y o ur diarr he a if y o u are ha vi n g m ore t ha n si x b o wel m o ve me nts per da y, b ut y o u s h o ul d n ot use a n y ot her di arr hea m e dicati o ns wit h o ut c o ntacti n g t he d oct or or st u d y assista nt. H o w l o n g will I be i n t he st u d y ? Y o u will b e i n t he st u d y f or ei g ht wee ks, wit h f o ur a d diti o nal wee ks of f oll o w u p if y o u res p o n d t o t he me dicati o n. Are t here re as o ns I mi g ht le a ve t his rese arc h st u d y e arl y ? Ta ki n g part i n t his rese arc h st u d y is y o ur decisi o n. Y o u ma y deci de t o st o p at a n y ti me. Y o u s h o ul d tell t he researc her if y o u d e ci de t o st o p a n d y o u will be a d vise d w het her a n y a d diti o nal tests ma y n ee d t o b e d o ne f or y o ur safet y. I n a d diti o n, t he rese arc hers or Ma y o ma y st o p y o u fr o m t a ki n g p art i n t his st u d y at a n y ti me if it is i n y o ur best i nterest, if y o u d o n ot f oll o w t he st u d y r ul es, or if t he st u d y is st o p pe d. Will a n y bi ol o gi c al s a m ple(s) be st ore d a n d use d f or rese arc h i n t he f ut ure ? N o. Y o ur sa m ples will be use d as descri be d f or t his st u d y, t he n t he y will be destr o ye d. 2 3 W h at are t he ris ks of t he st u d y ? As wit h a n y me dic ati o n, aller gic rea cti o ns t o b u des o ni de are a p ossi bilit y. Ot her a d verse e ve nts ass ociat e d wit h b u des o ni d e ma y i ncl u de he a dac he, r es pirat or y i nfecti o n, na usea or v o miti n g, bac k pai n, st o m ac h pai n, diz zi ness, gas, a n d fati g ue. W hile y o u are ta ki n g p art i n t his st u d y, y o u ar e at ris k f or t hese si de effects. Y o u s h o ul d tal k t o y o ur st u d y d oct or a n d/ or y o ur m e dical d oct or a b o ut t hese si de effects. T her e als o ma y be ot her si de effects t hat are n ot k n o w n. Ot h er dr u gs ma y be gi ve n t o ma ke si de effects less s eri o us a n d l ess u nc o mf orta ble. Ma n y si de effects g o a wa y s h ortl y after t he b u des o ni d e is st o p pe d, b ut i n s o me c ases si de effects ca n be seri o us or l o n g lasti n g. T he ris ks of dra wi n g bl o o d i ncl u de pai n, br uisi n g, or rarel y, i nfecti o n at t he site of t he bl o o d dra w. A fle xi ble si g m oi d osc o p y ma y ca use a b d o mi n al disc o mf ort a n d cr a m pi n g. T he ris k of seri o us si de effe cts s uc h as hea v y bl ee di n g a n d perf orati o n ( pr o d uci n g a h ole i n t he c ol o n) fr o m t he pr oce d ure is rare (l ess t ha n o n e perce nt). T here is n ot e n o u g h me dical i nf or mati o n t o k n o w w hat t h e ris ks mi g ht be t o a breast-fe d i nfa nt or t o a n u n b or n c hil d carri e d b y a w o ma n w h o ta kes part i n t his st u d y. T heref ore, pre g n a nt w o me n a n d n ursi n g m ot hers ma y n ot partici pate i n t his st u d y. F urt h er m or e all w o me n w h o ca n b ec o me pre g n a nt a n d ar e se x uall y acti ve, or t heir se x ual p art ners, m ust use birt h c o ntr ol meas ures w hile i n t his st u d y. T he f oll o wi n g birt h c o ntr ol meas ures are ac ce pta ble: birt h c o ntr ol pills, c o n d o ms, a dia p hra g m, or a n i ntra uteri ne de vice. Breast-f ee di n g m ot hers m ust st o p breast- fee di n g t o ta ke part i n t his st u d y. W o me n w h o ca n bec o m e pre g na nt m ust ha ve a pre g na nc y test bef ore t a ki n g part i n t his st u d y. F or t he pr e g na nc y test, bl o o d will be ta ke n fr o m a vei n i n y o ur ar m wit h a ne e dl e 1- 2 da ys bef ore t he st u d y. Y o u will be t ol d t he r es ults of t h e pre g na nc y test. If t he pre g na nc y t est is p ositi ve, y o u will n ot be a ble t o ta ke p art i n t he st u d y. If y o u bec o me pre g na nt d uri n g t h e st u d y, y o u m ust i m m e diatel y disc o nti n ue t he st u d y dr u g a n d i nf or m t he i n vesti g at ors. Are t here b e nefits t o t a ki n g p a rt i n t his st u d y ? T his st u d y ma y n ot ma ke y o ur healt h better. H o we ver, i n pre vi o us st u dies of b u des o ni de i n c olla ge n o us c olitis, 5 0- 1 0 0 % of partici pa nts res p o n de d t o t he me dicati o n wit h i m pr o ve me nt i n t heir diarr he a. T heref ore, t here is r eas o n t o e x pect t hat b u des o ni de ma y hel p y o ur diarr hea. H o we ver, t here is a c ha nce t hat y o u c o ul d r ecei ve t h e place b o me di cati o n, a n d t heref ore n o defi nite b e nefit ca n be e x pecte d fr o m partici p ati o n i n t his st u d y. W h at ot h er c h oices d o I h a ve if I d o n’t t a k e p art i n t his st u d y ? Y o u d o n ot ha ve t o be i n t his st u d y t o recei ve treat me nt f or y o ur c o n diti o n. If y o u deci de n ot t o partici pat e i n t his st u d y, a n ot her a nti- diarr hea or a nti-i nfla m mat or y 2 4 me dicati o n, i ncl u di n g b u des o ni de, ma y b e tri e d. Y o u s h o ul d tal k t o t he researc her a n d y o ur re g ular d oct or a b o ut eac h of y o ur c h oices bef ore y o u deci d e if y o u will ta ke part i n t his st u d y. Will I nee d t o p a y f or t he tests a n d pr o ce d u res ? Y o u will n ot nee d t o pa y f or a n y tests a n d pr oc e d ures t hat are d o ne j ust f or t his researc h st u d y. T hese t ests a n d pr oce d ures are t he fle xi ble si g m oi d os c o p y a n d c ol o n bi o psies, t he bl o o d w or k, a n d t he st o ol st u dies. H o we ver, y o u a n d/ or y o ur healt h pla n will nee d t o pa y f or all ot her tests a n d pr oce d ur es t hat y o u w o ul d n or mall y ha ve as part of y o ur re g ul ar me dic al care. T hese t ests a n d pr oce d ures are t he office visit, bl o o d a n d st o ol tests a n d t he si g m oi d osc o p y d o n e bef ore y o u are e nr olle d i nt o t he st u d y. T he st u d y me dicati o n will be pr o vi de d fre e of c har ge. W h at h a p pe ns if I a m i nj ure d bec a use I t o o k p art i n t his st u d y ? If y o u ha ve si de effects fr o m t he st u d y treat me nt, y o u nee d t o re p ort t he m t o t he researc her a n d y o ur re g ular d oct or, a n d y o u will be treate d as nee de d. Ma y o will bill y o u or y o ur i ns urer f or t hese ser vices at t h e us ual c har ge. Ma y o will n ot off er free me dical c are or pa y me nt f or a n y ba d si de effects fr o m ta ki n g part i n t his st u d y. Me dical ser vices nec essar y f or a res earc h relat e d ill ness or i nj ur y will be c o vere d b y Astra- Ze neca, t he st u d y s p o ns or, t o t h e e xt e nt t he y are n ot c o vere d b y y o ur healt h i ns ur a nce. W h at are m y ri g hts if I t a ke p a rt i n t his res e arc h st u d y ? Ta ki n g part i n t his res earc h st u d y d oes n ot t a ke a wa y a n y ot her ri g hts or be nefits y o u mi g ht ha v e if y o u di d n ot ta ke part i n t he st u d y. Ta ki n g part i n t his st u d y d oes n ot gi ve y o u a n y s peci al pri vile ges. Y o u will n ot be pe nalize d i n a n y wa y if y o u deci de n ot t o ta k e part or if y o u st o p after y o u start t he st u d y. S pecificall y, y o u d o n ot ha ve t o be i n t his st u d y t o recei v e or c o nti n ue t o recei ve me dical care fr o m Ma y o Cli nic. If y o u st o p t he st u d y y o u w o ul d still recei ve me di cal care f or y o ur c o n diti o n. Y o u will b e t ol d of i m p orta nt ne w fi n di n gs or a n y c ha n ges i n t he st u d y or pr oce d ures t hat ma y affect y o u or y o ur willi n g ness t o c o nti n ue i n t he st u d y. W h o c a n a ns wer m y q uesti o ns ? Y o u ma y tal k t o Dr. Par di at a n y ti me a b o ut a n y q uesti o n y o u h a ve o n t his st u d y. Y o u ma y c o ntact Dr. P ar di ( or a n ass ociate) b y calli n g t h e Ma y o o perat or at . 2 5 Y o u ca n get f urt her i nf or mati o n a b o ut Ma y o p olicies, t he c o n d uct of t his st u d y, or t he ri g hts of researc h s u bjects fr o m , A d mi nistrat or of t he Ma y o F o u n dati o n Office f or H u ma n Researc h Pr ote cti o n, tele p h o ne . A ut h oriz ati o n T o Use A n d Discl ose Pr otecte d He alt h I nf or m ati o n B y si g ni n g t his f or m, y o u a ut h orize Ma y o Cli nic R oc hes ter a n d t he i n vesti gat ors t o use a n d discl ose a n y i nf or mati o n cre ate d or c ollecte d i n t he c o urse of y o ur partici pati o n i n t his res earc h pr ot oc ol. T his i nf or m ati o n ma y be gi ve n t o ot her researc hers i n t his st u d y, re prese ntati ves of t he c o m pa n y s p o ns ori n g t he st u d y, or pri vat e, state or fe deral g o v er n me nt parti es res p o nsi ble f or o verse ei n g t his res earc h. T h ese ma y i ncl u de t he F o o d a n d Dr u g A d mi nistrati o n, t he Office f or H u ma n Resear c h Pr otecti o ns or ot her offices wit hi n t he De part me nt of He alt h a n d H u ma n Ser vi ces, a n d t he Ma y o F o u n dati o n Offic e f or H u ma n Resear c h Pr otecti o ns or ot her Ma y o gr o u ps i n v ol ve d i n pr otecti n g researc h s u bjects. T his i nf or mati o n will b e gi ve n o ut f or t he pr o per m o nit ori n g of t he st u d y, c hec ki n g t he acc urac y of st u d y data, a nal y zi n g t he st u d y data, a n d ot her p ur p oses necessar y f or t he pr o p er c o n d u ct a n d re p orti n g of t his st u d y. T his a ut h orizati o n l asts u ntil t he e n d of t he st u d y. Y o u ma y st o p t his a ut h orizati o n at a n y ti me e xce pt if Ma y o Cli nic R oc hester nee ds i nf or mati o n alrea d y c ollecte d t o e ns ure c o m plete a n d acc urat e st u d y res ults. T his mi g ht mea n t hat Ma y o ma y c o nti n ue t o use y o ur i nf or mati o n c olle cte d as part of t his st u d y e ve n after y o u ha ve t ol d us t o st o p. If t his is a researc h st u d y t hat als o i n v ol ves treat me nt, y o u ma y n o l o n ger be eli gi ble t o recei v e st u d y treat me nt if y o u tell Ma y o t o st o p usi n g t his i nf or mati o n. T h e o nl y wa y y o u ca n tell Ma y o t o st o p usi n g t he i nf or mati o n is i n writi n g a d dresse d as f oll o ws: Ma y o F o u n dati o n Office f or H u ma n R ese arc h Pr otecti o ns A T T N: N otice of Re v ocati o n of A ut h oriz ati o n 2 0 0 First St. S W R oc hester, M N 5 5 9 0 5 If t his i nf or mati o n is gi ve n o ut t o s o me o n e els e, t he i nf or mati o n ma y n o l o n ger b e pr otecte d b y fe deral pri vac y re g ulati o ns a n d m a y be gi ve n o ut b y t he pers o n or e ntit y t hat r ecei ves t he i nf or mati o n. A c o p y of t his f or m will be place d i n y o ur me dical rec or d. 2 6 I h a ve h a d a n o p p ort u nit y t o h a ve m y q uesti o ns a ns were d. I h a ve bee n gi ve n a c o p y of t his f or m. I a gree t o t a ke p art i n t his rese arc h st u d y. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( Date) ( Pri nte d Na me of Partici pa nt) ( Cli nic N u m ber) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( Si g nat ure of Partici pa nt) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( Date) ( Pri nte d Na me of I n di vi d ual O btai ni n g C o nse nt) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ( Si g nat ure of I n di vi d ual O btai ni n g C o nse nt)

2

arm 1: 9 mg daily arm 2: three tablets daily

[ 1, 2 ]

2

[ 10, 0 ]

intervention 1: Placebo, 3 tablets daily intervention 2: 9 mg daily (three tablets)

intervention 1: Placebo intervention 2: Budesonide

1

Rochester | Minnesota | United States | -92.4699 | 44.02163

0

NCT00217022

[ 3, 4 ]

146

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

false

This is a phase 3 clinical investigation. Patients who meet the eligibility criteria and provide signed informed consent will be randomized to receive one of two levels of Ferrlecit or oral iron in a 1:1:1 ratio.

null

Iron Deficiency Anemia

Anemia.

null

3

arm 1: 125 mg sodium ferric gluconate weekly x 8 weeks arm 2: 250 mg sodium ferric gluconate complex weekly x 4 weeks arm 3: 325 mg ferrous sulfate three times daily x 8 weeks

[ 0, 0, 1 ]

3

[ 0, 0, 0 ]

intervention 1: 125 mg weekly x 8 weeks intervention 2: 250 mg weekly x 4 intervention 3: 325 mg ferrous sulfate orally three times daily x 8 weeks

intervention 1: Sodium Ferric Gluconate Complex intervention 2: Sodium Ferric Gluconate Complex intervention 3: Oral Iron

43

0

NCT00223977

[ 5 ]

30

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

true

The purpose of this study is to evaluate the antidepressant effectiveness of Geodon for the treatment of patients diagnosed with Bipolar II disorder who are currently experiencing a major depressive episode.

Bipolar II disorder is largely unstudied, with much less known about its treatment in comparison to Bipolar I disorder. While established mood stabilizers treat and prevent subsequent episodes of hypomania, chronic or recurrent depressions are harder to treat or prevent. In general the treatment of depression in Bipolar II patients is often complicated and there is no clinical unanimity on what approaches to follow. Administration of proven antidepressants would seem most appropriate and are most often used, but their use often involves a number of difficulties. Among these are: * antidepressant efficacy is established for unipolar patients and extrapolation to Bipolar II patients is done without empirical support * Bipolar II patients can have switches into hypomanic behavior in response to antidepressant treatment given as monotherapy * even when mood stabilizers are concomitantly given, switches to hypomanic states still occur when antidepressants are added * antidepressants can cause cycle acceleration or induce rapid cycling when given to Bipolar II patients * non-response and loss of response are common reactions to antidepressants in Bipolar II patients This study will also assess the tolerability of Geodon in the treatment of patients diagnosed with Bipolar II disorder who currently meet criteria for a Major Depressive Episode by examining the incidence of adverse events and the withdrawal rate due to adverse events. This will be an open-label study. Subjects will be treated for 8 weeks with Geodon, starting at a dose of 20 mg twice per day. The maximum dose will be 60 mg twice per day. Subjects will have a physical exam, electrocardiogram (ECG), standard laboratory tests and a urine drug screen at the screen visit. Efficacy evaluations will include 17-item Hamilton Depression Scale, Hamilton Anxiety Scale (HAM-D), Montgomery-Asberg Depression Rating Scale, and the Young Mania Rating Scale. Social outcome will be measured with a quality-of-life scale (the Q-LES-Q). Overall efficacy will be rated using the Clinical Global Severity and Improvement Scales.

Bipolar II Disorder Major Depressive Episode

null

1

arm 1: Ziprasidone monotherapy, 20-60 mg BID.

[ 0 ]

1

[ 0 ]

intervention 1: Ziprasidone 20-60 mg BID, taken orally.

intervention 1: Ziprasidone

2

0

NCT00237666

[ 5 ]

42

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

0ALL

false

The purpose of the study is to determine whether an SSRI, paroxetine, improves social anxiety symptoms and alcohol use in individuals who drink to cope with social anxiety disorder.

Social anxiety disorder (also known as social phobia) is an Axis I anxiety disorder characterized by intense fear and avoidance of social or performance situations in which one might be scrutinized. Its onset is typically in the early teen years. It is the third most common mental disorder in the United States, exceeded in prevalence only by depression and alcoholism. Approximately 20% of the individuals with social anxiety disorder have alcohol problems. Anecdotal and empirical evidence suggests that alcohol is used by some socially anxious individuals to self-medicate anxiety symptoms, a practice that could lead to alcohol abuse and/or dependence. The proposed project further explores the self-medication hypothesis through the use of a double-blind, randomized, placebo-controlled clinical trial. Paroxetine (a selective serotonin reuptake inhibitor) is the drug to be used in the study. Individuals who drink alcohol to cope with social anxiety symptoms and who meet DSM-IV criteria for the dual-diagnoses of social anxiety disorder and alcohol use disorders will be enrolled in the trial. All individuals will be seeking treatment for social anxiety disorder. The treatment phase will last 16 weeks. Dosing will start at 20 mg/day (paroxetine or placebo) and will increase gradually to a maximum dose of 60 mg/day. Each week during treatment and at the end of the trial, assessments will be made with standard instruments to determine the effect of paroxetine (versus placebo) on social anxiety severity, alcohol use, and more specifically, the intentional use of alcohol to cope with social anxiety symptoms. Additionally, 6 month and 12 month follow-up interviews will be conducted. The overarching hypothesis is that because paroxetine will improve social anxiety severity, alcohol use and/or alcohol use for coping will also be reduced in the paroxetine-treated group.

Social Anxiety Disorder Social Phobia Alcohol Use Disorder Alcohol Abuse Alcohol Dependence

Pharmacotherapy Self medication

null

2

arm 1: Active medication containing the drug Paroxetine arm 2: A Placebo medication that appears just like the active medication but does not contain placebo

[ 0, 2 ]

2

[ 0, 0 ]

intervention 1: 16 weeks treatment; dosing will start at 20 mg/day paroxetine and will increase gradually to a maximum dose of 60 mg/day intervention 2: treatment phase will last 16 weeks; dosing will start at 20 mg/day (placebo) and will increase gradually to a maximum dose of 60 mg/day.

intervention 1: Paroxetine intervention 2: Placebo

1

Charleston | South Carolina | United States | -79.93275 | 32.77632

0

NCT00246441

[ 0 ]

20

NON_RANDOMIZED

PARALLEL

9OTHER

0NONE

true

2MALE

false

The purpose of this study is to evaluate the cerebral blood flow in subjects with high and low activity in the renin-angiotensin system (RAS).The renin-angiotensin system is a hormone system which is involved in the regulation of the blood pressure. Earlier studies have shown that high RAS activity is associated with a more pronounced cognitive impairment during hypoglycaemia compared to low RAS activity in both type 1 diabetic patients and healthy volunteers. We intend to examine brain activity by oxygen-15 labelled water-PET scanning during hypoglycaemia in response to cognitive function testing in 20 healthy male volunteers with high and low RAS activity, respectively

The purpose of this study is to evaluate the regional cerebral blood flow in subjects with high and low activity in the renin-angiotensin system (RAS). Earlier studies have shown that high RAS activity is associated with a more pronounced cognitive impairment during hypoglycaemia compared to low RAS activity in both type 1 diabetic patients and healthy volunteers. We intend to examine brain activity by oxygen-15 labelled water-PET scanning during hypoglycaemia in response to cognitive function testing in 20 healthy male volunteers with high and low RAS activity, respectively.

Hypoglycemia Cognitive Impairment

Hypoglycemia Cognitive impairment PET CalCAP

null

2

arm 1: 10 healthy men were characterized by having high basal RAS activity. arm 2: 10 healthy men were characterized by having either a low basal RAS activity.

[ 0, 0 ]

1

[ 0 ]

intervention 1: Hyperinsulinaemic induced hypoglycaemia

intervention 1: Human insulin

1

Hillerød | Hillerød | Denmark | 12.30081 | 55.92791

0

NCT00264641

[ 3 ]

110

NON_RANDOMIZED

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

true

The treatment of symptomatic, uncomplicated malaria caused by P. falciparum in adults.

null

Falciparum Malaria

null

1

arm 1: Single Arm, Open label study

[ 0 ]

1

[ 0 ]

intervention 1: dose of 2000 mg Azithromycin plus 600 mg chloroquine base

intervention 1: Azithromycin plus chloroquine

2

Tumaco | Departamento de Nariño | Colombia | -78.79275 | 1.79112 Bambolim | Goa | India | 73.8531 | 15.46361

0

NCT00282919

[ 3 ]

750

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

true

0ALL

false

This study tests whether stopping smoking by gradually cutting down first is more or less successful than stopping abruptly. We hypothesize that stopping by gradually cutting down first will produce more abstinence than stopping abruptly.

For cigarette smokers who intend to stop smoking, most treatment guidelines recommend abrupt cessation. There is evidence from some small studies that gradually reducing the number of cigarettes per day smoked may increase success in quitting. In this study, we will randomize smokers who want to quit smoking in the next 30 days to one of three groups: gradual reduction, abrupt cessation, and minimal intervention.

Smoking Cessation

Smoking Cessation Tobacco

null

3

arm 1: Intervention: Reduction Phone Counseling. Intervention: Pre-Quit Nicotine Lozenges. Intervention: Post-Quit Nicotine Lozenges. arm 2: Intervention: Abrupt Phone Counseling. Intervention: Post-Quit Nicotine Lozenges. arm 3: Intervention: Minimal Abrupt Phone Counseling. Intervention: Post-Quit Nicotine Lozenges.

[ 0, 1, 1 ]

5

[ 5, 5, 5, 0, 0 ]

intervention 1: Counseling of smokers to undergo gradual reduction in cigarettes per day prior to quit date. This includes 5 counseling calls: 3 calls focused on reduction prior to the quit date, 1 call two days prior to the quit date to discuss common strategies for preparing to quit, and 1 call two days after the quit date to discuss relapse prevention. Telephone counseling also discusses the proper use of nicotine lozenges during reduction and after the quit date. intervention 2: Counseling of smokers to set a quit date and not change cigarettes per day prior to quit date. This includes 5 counseling calls: 1 to set a quit date, 1 two days prior to the quit date to discuss common strategies for preparing to quit, and 3 after the quit date to discuss relapse prevention. Telephone counseling also discusses the proper use of nicotine lozenges after the quit date. intervention 3: Minimal counseling to mimic intervention at a primary care office. This includes 2 counseling calls: 1 to set a quit date and 1 two days after the quit date to discuss relapse prevention. Telephone counseling also discusses the proper use of nicotine lozenges after the quit date. intervention 4: 2 mg lozenges for participants usually smoke their first cigarette more than 30 minutes after awaking. 4 mg lozenge for participants who usually smoke their first cigarette less than 30 minutes after awaking. Replace each forgone cigarette during reduction with one lozenge. Use additional lozenges to combat cravings to smoke. intervention 5: 2 mg lozenges for participants usually smoke their first cigarette more than 30 minutes after awaking. 4 mg lozenge for participants who usually smoke their first cigarette less than 30 minutes after awaking. Replace each forgone cigarette while abstinent with one lozenge. Use additional lozenges to combat cravings to smoke.

intervention 1: Reduction Phone Counseling intervention 2: Abrupt Phone Counseling intervention 3: Minimal Abrupt Phone Counseling intervention 4: Pre-Quit Nicotine Lozenges intervention 5: Post-Quit Nicotine Lozenges

1

Burlington | Vermont | United States | -73.21207 | 44.47588

0

NCT00297492

[ 4 ]

1,179

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

null

This study will assess the safety and efficacy of one-day famciclovir (1000 mg twice a day (b.i.d)) in reducing the duration of genital herpes lesions and the associated symptoms compared to three-day treatment with valacyclovir (500 mg capsule b.i.d).

null

Genital Herpes

Herpes simplex genital herpes famciclovir valacyclovir Recurrent genital herpes

null

2

arm 1: Patients received Famciclovir 1000 mg (2 x 500 mg tablets) twice a day for one day. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions and the second dose approximately 12 hours later. Patients also received 1 valacyclovir placebo capsule, beginning with the first famciclovir dose, twice a day for 3 days, each taken about 12 hours apart. arm 2: Patients received Valacyclovir 500 mg capsule twice a day approximately 12 hours apart for 3 consecutive days. The first dose was to be taken within 6 hours after onset of prodromal symptoms or genital herpes lesions. On the first day patients also received 2 famciclovir placebo tablets taken with the first 2 doses of Valacyclovir.

[ 0, 1 ]

4

[ 0, 0, 0, 0 ]

intervention 1: Famciclovir 500 mg tablet intervention 2: Valacyclovir 500 mg capsule intervention 3: Famciclovir placebo, matching in size, color and forms of famciclovir tablet. intervention 4: Valacyclovir placebo, matching in size, color and forms of valacyclovir capsule.

intervention 1: Famciclovir intervention 2: Valacyclovir intervention 3: Placebo matching famciclovir intervention 4: Placebo matching valacyclovir

66

0

NCT00306787

[ 4 ]

933

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

null

The aim of the study is to compare the efficacy of roflumilast on pulmonary function and symptomatic parameters in patients with chronic obstructive pulmonary disease (COPD) during concomitant administration of salmeterol. The study duration will last up to 28 weeks. The study will provide further data on safety and tolerability of roflumilast.

null

Chronic Obstructive Pulmonary Disease (COPD)

Roflumilast Salmeterol COPD Chronic obstructive pulmonary disease

null

2

arm 1: Roflumilast 500 µg underlying medication: salmeterol 50 μg, twice daily, inhaled arm 2: Placebo underlying medication: salmeterol 50 μg, twice daily, inhaled

[ 1, 2 ]

2

[ 0, 0 ]

intervention 1: 500 µg, once daily, oral administration in the morning intervention 2: once daily

intervention 1: Roflumilast intervention 2: Placebo

134

Linz | N/A | Austria | 14.28611 | 48.30639 Neusiedl/See | N/A | Austria | N/A | N/A Perg | N/A | Austria | 14.63333 | 48.25 Salzburg | N/A | Austria | 13.04399 | 47.79941 Sankt Pölten | N/A | Austria | 15.63333 | 48.2 Steyr | N/A | Austria | 14.42127 | 48.04274 Vienna | N/A | Austria | 16.37208 | 48.20849 Vienna | N/A | Austria | 16.37208 | 48.20849 Vienna | N/A | Austria | 16.37208 | 48.20849 Wiener Neustadt | N/A | Austria | 16.23196 | 47.80485 Zwettl Stadt | N/A | Austria | 15.16714 | 48.60726 Arlon | N/A | Belgium | 5.81667 | 49.68333 Brussels | N/A | Belgium | 4.34878 | 50.85045 Brussels | N/A | Belgium | 4.34878 | 50.85045 Duffel | N/A | Belgium | 4.50903 | 51.09554 Genk | N/A | Belgium | 5.50082 | 50.965 Gilly | N/A | Belgium | 4.4789 | 50.42449 Halen | N/A | Belgium | 5.11096 | 50.94837 Jette | N/A | Belgium | 4.33419 | 50.87309 Leuven | N/A | Belgium | 4.70093 | 50.87959 Liège | N/A | Belgium | 5.56749 | 50.63373 Malmedy | N/A | Belgium | 6.02794 | 50.42686 Montigny-le-Tilleul | N/A | Belgium | 4.37582 | 50.38056 Namur | N/A | Belgium | 4.86746 | 50.4669 Veurne | N/A | Belgium | 2.66803 | 51.07316 Ajax, Ontario | N/A | Canada | -79.03288 | 43.85012 Halifax, N.S. | N/A | Canada | -63.57688 | 44.64269 Hamilton | N/A | Canada | -79.84963 | 43.25011 Hamilton, Ontario | N/A | Canada | -79.84963 | 43.25011 Laval | N/A | Canada | -73.692 | 45.56995 London | N/A | Canada | -81.23304 | 42.98339 Mirabel | N/A | Canada | -74.08251 | 45.65008 Montreal | N/A | Canada | -73.58781 | 45.50884 Montreal | N/A | Canada | -73.58781 | 45.50884 Montreal, PQ | N/A | Canada | -73.58781 | 45.50884 New Market, on | N/A | Canada | -66.91905 | 45.82499 North Bay | N/A | Canada | -79.46633 | 46.3168 Ontario | N/A | Canada | N/A | N/A Ottawa | N/A | Canada | -75.69812 | 45.41117 Québec | N/A | Canada | -71.21454 | 46.81228 Regina, Saskatchewan | N/A | Canada | -104.6178 | 50.45008 Saint John | N/A | Canada | -66.05616 | 45.27076 Sainte-Foy, Quebec | N/A | Canada | N/A | N/A Saskatoon SK | N/A | Canada | N/A | N/A Sherbrooke, PQ | N/A | Canada | -71.89908 | 45.40008 Toronto, on | N/A | Canada | -79.39864 | 43.70643 Toronto, on | N/A | Canada | -79.39864 | 43.70643 Vancouver, BC | N/A | Canada | -123.11934 | 49.24966 Windsor | N/A | Canada | -83.01654 | 42.30008 Winnipeg MB | N/A | Canada | N/A | N/A Woodstock | N/A | Canada | -80.7497 | 43.13339 Beausoleil | N/A | France | 7.4225 | 43.74311 Beuvry | N/A | France | 2.68541 | 50.51674 Chauny | N/A | France | 3.21857 | 49.61514 Grasse | N/A | France | 6.92537 | 43.65783 Grenoble | N/A | France | 5.71479 | 45.17869 Lille | N/A | France | 3.05858 | 50.63297 Lyon | N/A | France | 4.84671 | 45.74846 Martigues | N/A | France | 5.05526 | 43.40735 Montpellier | N/A | France | 3.87635 | 43.61093 Nantes | N/A | France | -1.55336 | 47.21725 Nice | N/A | France | 7.26608 | 43.70313 Nice | N/A | France | 7.26608 | 43.70313 Nîmes | N/A | France | 4.35788 | 43.83665 Saint-Laurent-du-Var | N/A | France | 7.19 | 43.67323 Saint-Quentin | N/A | France | 3.28757 | 49.84889 Trélazé | N/A | France | -0.46652 | 47.44629 Aschaffenburg | N/A | Germany | 9.15214 | 49.97704 Bochum | N/A | Germany | 7.21648 | 51.48165 Bonn | N/A | Germany | 7.09549 | 50.73438 Cologne | N/A | Germany | 6.95 | 50.93333 Geesthacht | N/A | Germany | 10.3779 | 53.43575 Gelnhausen | N/A | Germany | 9.18742 | 50.20164 Großhansdorf | N/A | Germany | 10.28333 | 53.66667 Hanover | N/A | Germany | 9.73322 | 52.37052 Koblenz | N/A | Germany | 7.57883 | 50.35357 Marburg | N/A | Germany | 8.77069 | 50.80904 Saarbrücken | N/A | Germany | 7.00982 | 49.23262 Schwetzingen | N/A | Germany | 8.5823 | 49.38217 Sinsheim | N/A | Germany | 8.87867 | 49.2529 Surwold | N/A | Germany | 7.51534 | 52.978 Witten | N/A | Germany | 7.35258 | 51.44362 Würzburg | N/A | Germany | 9.95121 | 49.79391 Bari | N/A | Italy | 16.86982 | 41.12066 Bologna | N/A | Italy | 11.33875 | 44.49381 Catania | N/A | Italy | 15.07041 | 37.49223 Cisanello (PI) | N/A | Italy | N/A | N/A Genova | N/A | Italy | 11.87211 | 45.21604 Livorno | N/A | Italy | 10.32615 | 43.54427 Milan | N/A | Italy | 12.59836 | 42.78235 Pordenone | N/A | Italy | 12.66051 | 45.95689 Roma | N/A | Italy | 11.10642 | 44.99364 Saluzzo (CN) | N/A | Italy | 7.49309 | 44.64671 Torino | N/A | Italy | 11.99138 | 44.88856 Tradate (VA) | N/A | Italy | 8.90763 | 45.70843 Verona | N/A | Italy | 10.9938 | 45.43854 Vittorio Veneto (TV) | N/A | Italy | 12.30065 | 45.98026 Alkmaar | N/A | Netherlands | 4.74861 | 52.63167 Almelo | N/A | Netherlands | 6.6625 | 52.35667 Eindhoven | N/A | Netherlands | 5.47778 | 51.44083 Helmond | N/A | Netherlands | 5.66111 | 51.48167 Schiedam | N/A | Netherlands | 4.38889 | 51.91917 Zwolle | N/A | Netherlands | 6.09444 | 52.5125 Cape Town | N/A | South Africa | 18.42322 | -33.92584 Alicante | N/A | Spain | -0.48149 | 38.34517 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 Elche (Alicante) | N/A | Spain | -0.70107 | 38.26218 Fuentesnuevas, Ponferrada (León) | N/A | Spain | N/A | N/A Guadalajara | N/A | Spain | -3.16185 | 40.62862 Laredo (Cantabria) | N/A | Spain | -3.41613 | 43.4098 Mataró, Barcelona | N/A | Spain | N/A | N/A Petrer (Alicante) | N/A | Spain | -0.77549 | 38.48289 Sabadell | N/A | Spain | 2.10942 | 41.54329 Tarrasa (Barcelona) | N/A | Spain | N/A | N/A Torrelavega (Cantabria) | N/A | Spain | -4.04785 | 43.34943 Belfast | N/A | United Kingdom | -5.92541 | 54.59682 Belfast | N/A | United Kingdom | -5.92541 | 54.59682 Belfast | N/A | United Kingdom | -5.92541 | 54.59682 Bexhill-on-Sea, East Sussex | N/A | United Kingdom | 0.47095 | 50.85023 Bradford | N/A | United Kingdom | -1.75206 | 53.79391 Bradford on Avon, Wiltshire | N/A | United Kingdom | -2.25065 | 51.34772 Chesterfield Derbyshire | N/A | United Kingdom | N/A | N/A Coleraine | N/A | United Kingdom | -6.66667 | 55.13333 Cookstown | N/A | United Kingdom | -6.74595 | 54.64305 East Sussex | N/A | United Kingdom | N/A | N/A Edinburgh | N/A | United Kingdom | -3.19648 | 55.95206 Glasgow | N/A | United Kingdom | -4.25763 | 55.86515 Hastings | N/A | United Kingdom | 0.58009 | 50.85568 Middlessex | N/A | United Kingdom | N/A | N/A Sunbury on Thames, Middlessex | N/A | United Kingdom | -0.41817 | 51.40424 Watford | N/A | United Kingdom | -0.39602 | 51.65531

0

NCT00313209

[ 2 ]

15

NON_RANDOMIZED

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

null

The primary objective of this study is to determine the dose limiting toxicity and maximum tolerated dose of E7389 in patients with solid tumors. The secondary objectives are to investigate the pharmacokinetics, safety, estimated recommended dose, and anti-tumor effects (in evaluable cases) of E7389 in patients with solid tumors.

null

Cancer

Cancer Tumors Phase I E7389

null

1

arm 1: None

[ 0 ]

1

[ 0 ]

intervention 1: E7389 will be administered intravenously on Days 1 and 8 of a 21 day cycle. The initial dose level will be 0.7 mg/m2, with planned dose levels of 1.0, 1.4, 2.0 mg/m2.

intervention 1: E7389

1

Kashiwa | Chiba | Japan | 139.97732 | 35.86224

0

NCT00326950

[ 3 ]

30

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

false

The purpose of this trial is to to determine the safety and effectiveness of therapeutic combination - Clofarabine and Cytarabine for the treatment of AML and MDS.

Previous studies of Clofarabine and Cytarabine combination treatment in adult AML and MDS patients showed promising results. This study is done to confirm the findings from previous studies. Primary objective is to determine the overall response rate (complete response \[CR\] plus partial response \[PR\]); secondary objective of this study is to characterize and quantify the toxicity profile associated with clofarabine plus cytarabine treatment. A maximum of 35 patients will be treated on this study. They will receive 5 consecutive days of clofarabine intra venous infusion (IVI) followed 4 hours later by cytarabine IVI.Patients will receive up to a maximum of 4 cycles of study treatment. Next cycle will start approximately 4 weeks after Day 1 of previous cycle.No other investigational or commercial agents including chemotherapy, radiotherapy, or immunotherapy may be administered to patients enrolled in this study with the intention of treating the underlying malignancy Patients will remain on study, and be monitored until 4 months have elapsed from the beginning date of their last cycle of treatment.

Acute Myelogenous Leukemia Myelodysplastic Syndromes Chronic Myelogenous Leukemia

AML MDS CML Relapsed Refractory Chemo treatment Clofarabine Cytarabine standard or poor cytogenetic risk AML untreated high-risk (>10% blasts) MDS CML in accelerated phase or blast crisis Elderly AML patients with risk of anthracycline toxicity

null

1

arm 1: Five consecutive days of clofarabine 40 mg/m\^2 IVI over 1 hour followed 4 hours later by cytarabine 1000 mg/m\^2 IVI over 2 hours

[ 0 ]

1

[ 0 ]

intervention 1: Phase II Trial of Clofarabine and Cytarabine in Relapsed Standard-Risk AML and Untreated High-Risk MDS in Adult Patients, and Untreated AML in selected Elderly Patients at high risk of anthracycline toxicity

intervention 1: Clofarabine and Cytarabine

1

Dallas | Texas | United States | -96.80667 | 32.78306

0

NCT00334074

[ 3 ]

121

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

true

This study will provide preliminary data on the dose and dose interval related effects of intravitreally administered Avastin on retinal thickness and visual acuity in subjects with Diabetic Macular Edema (DME) to aid in planning a phase 3 trial. In addition, this study will provide preliminary data on the safety of intravitreally administered Avastin in subjects with DME.

Diabetic retinopathy is a major cause of visual impairment in the United States. Diabetic macular edema (DME) is a manifestation of diabetic retinopathy that produces loss of central vision. Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) estimate that after 15 years of known diabetes, the prevalence of diabetic macular edema is approximately 20% in patients with type 1 diabetes mellitus (DM), 25% in patients with type 2 DM who are taking insulin, and 14% in patients with type 2 DM who do not take insulin. In a review of three early studies concerning the natural history of diabetic macular edema, Ferris and Patz found that 53% of 135 eyes with diabetic macular edema, presumably all involving the center of the macula, lost two or more lines of visual acuity over a two year period. In the Early Treatment Diabetic Retinopathy Study (ETDRS), 33% of 221 untreated eyes available for follow-up at the 3-year visit, all with edema involving the center of the macula at baseline, had experienced a 15 or more letter decrease in visual acuity score (equivalent to a doubling of the visual angle, e.g., 20/25 to 20/50, and termed "moderate visual loss"). In the ETDRS, focal photocoagulation (direct treatment to microaneurysms and grid treatment to diffuse edema) of eyes with clinically significant macular edema (CSME) reduced the risk of moderate visual loss by approximately 50% (from 24% to 12%, three years after initiation of treatment). Therefore, 12% of treated eyes developed moderate visual loss in spite of treatment. Furthermore, approximately 40% of treated eyes that had retinal thickening involving the center of the macula at baseline still had thickening involving the center at 12 months, as did 25% of treated eyes at 36 months. Although several treatment modalities are currently under investigation, the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation, as demonstrated by the ETDRS, intensive glycemic control, as demonstrated by the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) and blood pressure control, as demonstrated by the UKPDS. In the DCCT, intensive glucose control reduced the risk of onset of diabetic macular edema by 23% compared with conventional treatment. Long-term follow-up of patients in the DCCT show a sustained effect of intensive glucose control, with a 58% risk reduction in the development of diabetic macular edema for the DCCT patients followed in the Epidemiology of Diabetes Interventions and Complications Study. The frequency of an unsatisfactory outcome with respect to proportion with vision improvement following laser photocoagulation in some eyes with diabetic macular edema has prompted interest in other treatment modalities. One such treatment is pars plana vitrectomy. These studies suggest that vitreomacular traction, or the vitreous itself, may play a role in increased retinal vascular permeability. Removal of the vitreous or relief of mechanical traction with vitrectomy and membrane stripping may be followed by substantial resolution of macular edema and corresponding improvement in visual acuity. However, this treatment may be applicable only to a specific subset of eyes with diabetic macular edema that have a component of vitreomacular traction contributing to the edema. It also requires a complex surgical intervention with its inherent risks, recovery time, and expense. Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and use of intravitreal corticosteroids are under investigation. The use of antibodies targeted at vascular endothelial growth factor (VEGF), such as in the current study, is another treatment modality that has generated considerable interest, and is currently being investigated in phase 3 trials of choroidal neovascularization in age-related macular degeneration (with pegaptanib or ranibizumab) or diabetic macular edema (with pegaptanib). Increased VEGF levels have been demonstrated in the retina and vitreous of human eyes with diabetic retinopathy. VEGF, also known as vascular permeability factor, has been demonstrated to increase vessel permeability by increasing the phosphorylation of tight junction proteins, and has been shown to increase retinal vascular permeability in in vivo models. Anti-VEGF therapy, therefore, may represent a useful therapeutic modality which targets the underlying pathogenesis of diabetic macular edema. Bevacizumab is currently approved for the treatment of metastatic colorectal cancer, and published case reports and widespread clinical use have suggested its efficacy in the treatment of neovascular age-related macular degeneration and macular edema associated with diabetes and central retinal vein occlusion. To date, no evidence of ocular inflammation or other adverse events has been noted in association with intravitreal injection of bevacizumab. However, a study has not been conducted to evaluate its efficacy and safety. In view of the widespread use of bevacizumab, such a study is important to conduct. From a public health perspective, an intravitreal bevacizumab study is also important to conduct because of the relatively low cost of the bevacizumab drug. As noted earlier, bevacizumab is marketed for systemic use for colon cancer. The dose used in the eye is a fraction of the systemic dose and costs $25 to $50 per dose. The two doses of bevacizumab being evaluated in this study will be 1.25 mg, which is the dose that has most commonly been used in clinical practice, and 2.5 mg, which has also been used though less commonly. A lower dose than 1.25 mg would create difficulties with dilution and the accuracy of injection of a small volume. The optimal interval for the bevacizumab doses is not known. Six weeks has been selected for this study as it is not believed that the effect will last longer than this. Retinal thickening and visual acuity will be measured at 3 and 6 weeks to provide the requisite information to judge the duration of effect. There is expected to be a beneficial cumulative effect of multiple doses. A total of two doses, spaced 6 weeks apart, was selected for the study with the primary outcome 3 weeks after the second dose. The decision as to whether to proceed to a phase 3 trial will be based on the observation of a substantial reduction in retinal thickening in the bevacizumab-treated eyes compared with the laser-treated eyes and at least a suggestion of benefit on visual acuity, plus a safety profile of minimal risk. Description: The study involves the enrollment of subjects over 18 years of age with diabetic macular edema. Subjects will have one study eye randomly assigned with equal probability (stratified by visual acuity) to one of 5 treatment groups: Laser photocoagulation at baseline 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks) 1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks Follow-up includes 10 visits at 4 days, 3 weeks, 6 weeks, 4 days following 6 weeks, 9 weeks, 12 weeks, 18 weeks, 24 weeks, 41 weeks and 70 weeks. At each visit, visual acuity and ocular exams are completed on both eyes, and an OCT is performed on the study eye (except at the 4-day visits). During the first 12 weeks, no other treatment for DME is given. During weeks 13-24, treatment depends on the response to the treatment given during the first 12 weeks. After 24 weeks, follow-up is for safety and treatment is at the investigator's discretion.

Diabetic Retinopathy

diabetic macular edema avastin bevacizumab anti-VEGF retinal thickness visual acuity DME

null

5

arm 1: Laser photocoagulation at baseline arm 2: 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks arm 3: 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks arm 4: 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks) arm 5: 1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks

[ 1, 0, 0, 0, 0 ]

5

[ 3, 0, 0, 0, 0 ]

intervention 1: Laser photocoagulation at baseline; If edema present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart intervention 2: 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks intervention 3: 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks intervention 4: 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks) intervention 5: 1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks

intervention 1: Laser Photocoagulation intervention 2: Bevacizumab intervention 3: Bevacizumab intervention 4: Bevacizumab intervention 5: Bevacizumab

34

0

NCT00336323

[ 3 ]

263

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

true

Study the effectiveness of telaprevir (VX-950) in combination with Pegylated Interferon Alfa 2a (Peg-IFN-alfa-2a) and Ribavirin (RBV) in reducing plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels

null

Chronic Hepatitis C

null

4

arm 1: Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (\<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (\>=) 75 kg, for 48 weeks. arm 2: Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. arm 3: Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 24 weeks. arm 4: Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 12 weeks.

[ 2, 0, 0, 0 ]

4

[ 0, 0, 0, 10 ]

intervention 1: tablet intervention 2: tablet intervention 3: Solution for injection intervention 4: matching placebo tablet

intervention 1: Telaprevir intervention 2: Ribavirin intervention 3: Pegylated Interferon Alfa 2a intervention 4: Placebo

37

0

NCT00336479

[ 0 ]

16

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

false

The study objective is to assess the long term safety and effectiveness of Enteryx device in commercial use. The long-term effects beyond one year of treatment with Enteryx have not been established.

The Enteryx procedure kit is indicated for endoscopic injection into the region of the lower esophageal sphincter (LES) for the treatment of symptoms due to gastroesophageal reflux disease (GERD) symptoms in patients responding to and requiring daily pharmacological therapy with proton pump inhibitors (PPI's). The study design consists of two parts, Part A and Part B. Part A will enroll patients who received Enteryx treatments after approval and Part B will enroll patients previously enrolled and treated in the IDE study #G000065. In total there will be at least 300 patients enrolled in Part A and Part B with 36 months of follow-up Part A: Approximately 150 to 200 patients will be enrolled from 22 centers. After patients have determined with their physicians that Enteryx is an appropriate course of therapy for their GERD symptoms, they will be asked to participate in this trial. Patients will be followed for adverse events, medication use, and GERD-HRQL symptoms at baseline, day of treatment, one month, six months, twelve months, twenty-four months, and thirty-six months. The final study visit will be thirty-six months after the last Enteryx injection. In addition, all Part A patients will be contacted by the Site at least quarterly to obtain current adverse event information. This adverse event information will be solicited from the Site by the Sponsor at least quarterly. Part B: All US IDE patients (approximately 150 patients) will be asked to enroll. Patients will be followed for adverse events, medication use, and GERD-HRQL symptoms at two visits beyond the follow-up prescribed in the IDE study, namely 24 and 36 months after the last Enteryx injection received in the IDE study. Parts A and B: There will be a breakdown of adverse events based on retreatment status. Any subsequent procedures or interventions related to GERD or Enteryx, whether surgical (such as fundoplication) or non-surgical (such as an alternative endoscopic treatment for GERD), will be collected and reported. H0: (Null hypothesis): Proportion of patients exhibiting clinically significant improvement in reduction of PPI therapy ≤ 0.5 Ha: (Alt. hypothesis): Proportion of patients exhibiting clinically significant improvement in reduction of PPI therapy \> 0.5 The Sponsor will examine the proportion of patients who have clinically significant reduction in PPI therapy at the 12, 24 and 36 month follow-ups, in an identical manner to that used for the patients in the IDE trial. The "clinically significant reduction" is defined as either elimination of medication use or reduction in dosage of ≥50%. The criterion for success is defined as more than half of patients demonstrating this degree of medication reduction. The hypothesis is tested by p-value and construction of the exact 95% Clopper-Pearson confidence intervals around the observed proportion of patients who meet the criterion for success. The longitudinal post-procedure follow-up data across time (repeated measures) will be analyzed to determine patterns and trends for all primary endpoints. The hypothesis stated above will also be evaluated in the subset of patients that underwent retreatment prior to amendment v.14Oct05.

Gastroesophageal Reflux

GERD Gastroesophageal Reflux Disease Reflux Enteryx

null

1

arm 1: Those receiving Enteryx treatment

[ 0 ]

1

[ 0 ]

intervention 1: None

intervention 1: Enteryx

1

Boston | Massachusetts | United States | -71.05977 | 42.35843

0

NCT00346905

[ 5 ]

37

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

false

The primary purpose of the study is to compare the effect of perioperative (the time period describing the duration of a participants surgical procedure) administration of PROCRIT to that of Standard of Care (SOC) on the proportion of participants receiving pRBC (packed red blood cells) transfusions (from the day of surgery to the day of hospital discharge) in participants undergoing elective major abdominal and/or pelvic surgery. Standard of Care is defined as the treatment of participants according to the hospital or institution's policy, but where participants will not receive PROCRIT (Epoetin alfa) or any other erythropoiesis-stimulating agents (ESAs) (agents that stimulate the production of red blood cells in the bone marrow).

This is a randomized (the study medication is assigned by chance), parallel-arm (each group of participants will be treated at the same time), open-label (all people know the identity of the intervention), multicenter study. The study consists of screening phase of 21 days, treatment phase of 15 days, follow-up phase of 28 days. Approximately 110 participants undergoing elective major abdominal and/or pelvic surgery will be enrolled. During the Treatment Phase, eligible participants will be randomly assigned (participants are assigned to a treatment group based on chance) in a 1:1 ratio to either PROCRIT (Epoetin alfa) or the Standard of Care (SOC) group that will not receive any erythropoiesis-stimulating agents (ESAs). Participants will undergo surgery during the Treatment Phase. After surgery, all participants will stay in the study for 4 days (or until hospital discharge) and followed for an additional 28 days (Follow-up Phase). Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination which will be monitored throughout the study. The duration of the study for each participant will be approximately 64 days.

Hemostasis, Surgical

Hemostasis, Surgical Epoetin alfa Surgery Abdomen Pelvis PROCRIT pRBC Blood transfusion Packed red blood cell transfusion

null

2

arm 1: Participants will receive PROCRIT (epoetin alfa). arm 2: Participants will receive standard of care.

[ 0, 0 ]

2

[ 0, 0 ]

intervention 1: Participants will receive epoetin alfa 300 IU/kg once daily subcutaneously for 10 days prior to surgery, on the day of surgery, and for four days after surgery. intervention 2: Participants will receive standard of care based on the Institution's treatment policy.

intervention 1: Epoetin alfa intervention 2: Standard of Care

0

null

0

NCT00350519

[ 2, 3 ]

17

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

true

Purpose: The primary objective of this study is to determine if chemotherapy with carboplatin and temozolomide significantly affects the response rates, or size of disease, in patients with brain metastases, originating from cancer in other parts of the body, compared to patients who have already been treated with radiation. Survival, causes of death, recurrence of disease in the central nervous system, toxicity, and quality of life will all be measured as secondary objective in this study.

Rationale: Surgery and radiation are often used as treatments for brain metastases, or tumors in the brain that originate from other parts of the body. It is currently unknown whether patient survival or time to progression would experience additional benefits through the addition of chemotherapy. Previous research does appear to suggest that a chemotherapy regimen may improve outcomes of patients with brain metastases previously treated with radiation. The current study further evaluates this research question by providing patients with recurrent or symptomatic residual brain metastases with carboplatin and temozolomide, two chemotherapy agents. Temozolomide has demonstrated clinical antitumor efficacy against malignant gliomas and has been tested with some efficacy against several other types of cancer. This drug appears to have less adverse effects compared to other commonly used cancer drugs. Recent research indicates that temozolomide also has some efficacy against brain metastases. In addition, previous research indicates carboplatin's lack of severe toxicity in patients with this disease. Treatment: Study participants will be treated with carboplatin and temozolomide. Carboplatin will be administered through intravenous infusions. Temozolomide will be given through oral pills. Before these drugs are administered, study participants will undergo a pre-treatment evaluation with physical and neuropsychological examinations, neuro-imaging, laboratory tests, quality of life assessment, and other procedures. Carboplatin will be given for two consecutive days. Temozolomide will be taken by study participants daily for five consecutive days. Both of these treatment schedules will be repeated every 28 days. Several tests and exams will be given throughout the study to closely monitor patients. Study treatments will be discontinued due to disease growth or unacceptable adverse events.

Brain Tumor Brain Metastases

Recurrent Symptomatic

null

1

arm 1: Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin

[ 0 ]

2

[ 0, 0 ]

intervention 1: IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2. intervention 2: 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks.

intervention 1: carboplatin intervention 2: temozolomide

1

Columbus | Ohio | United States | -82.99879 | 39.96118

0

NCT00362817

[ 4 ]

901

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

null

Evaluate the systolic blood pressure lowering effect of aliskiren 150mg and 300mg compared to ramipril 5mg and 10mg in elderly patients with essential systolic hypertension.

null

Hypertension

Systolic hypertension hypertension aliskiren blood pressure ramipril HTN

null

2

arm 1: Aliskiren 150 mg; aliskiren 300 mg; aliskiren 300mg + hydrochlorothiazide 12.5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; aliskiren 300 mg + hydrochlorothiazide 25 mg + amlodipine 10 mg arm 2: Ramipril 5 mg; Ramipril 10 mg; Ramipril 10 mg + hydrochlorothiazide 12.5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 5 mg; Ramipril 10 mg + hydrochlorothiazide 25 mg + amlodipine 10mg

[ 0, 1 ]

4

[ 0, 0, 0, 0 ]

intervention 1: Aliskiren 150 mg and 300 mg tablets taken orally, once a day in the morning intervention 2: Ramipril 5 mg and 10 mg capsules taken orally, once a day in the morning intervention 3: Hydrochlorothiazide 12.5 or 25 mg capsules taken orally, once a day in the morning intervention 4: Amlodipine 5 mg or 10 mg tablets taken orally, once a day in the morning

intervention 1: Aliskiren intervention 2: Ramipril intervention 3: Hydrochlorothiazide intervention 4: Amlodipine

1

East Hanover | New Jersey | United States | -74.36487 | 40.8201

0

NCT00368277

[ 4 ]

138

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

null

The objective of this study is to evaluate the efficacy, acceptability, and safety of Axid Oral Solution versus placebo in the treatment of gastroesophageal reflux disease (GERD) in infants age 30 days up to 1 year.

null

Gastroesophageal Reflux Disease GERD Heartburn

gastroesophageal reflux disease GERD heartburn

null

3

arm 1: None arm 2: None arm 3: None

[ 0, 0, 3 ]

3

[ 0, 0, 0 ]

intervention 1: nizatidine (axid) intervention 2: nizatidine (axid) intervention 3: placebo

26

0

NCT00373334

[ 3 ]

47

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

1FEMALE

true

The purpose of this study is to determine whether the investigational drug catumaxomab delivered in the planned treatment schedule is a safe and effective treatment for women with advanced ovarian cancer who experience a complete response to chemotherapy.

A multi-center, phase II study of catumaxomab in ovarian cancer patients who experience a complete response to chemotherapy. Each eligible patient will receive four ascending doses of catumaxomab, administered intraperitoneally via an indwelling catheter or port. Catumaxomab will be administered as a 3-hour constant rate infusion with a dosing interval of 3-4 days. Each patient will participate in this study for up to 4 months (includes the baseline screening period, 11 to 21 days treatment period, and up to 90 days/3 months follow-up), with post-study follow-up every 3 months for 2 years. Catumaxomab is a trifunctional antibody targeting epithelial cell adhesion molecule (EpCAM) on tumor cells and CD3 (cluster of differentiation 3) on T cells. Trifunctional antibodies represent a new concept for targeted anticancer therapy. This new antibody class has the capability to redirect T cells and accessory cells (e.g. macrophages, dendritic cells \[DCs\] and natural killer \[NK\] cells) to the tumor site. According to preclinical data, trifunctional antibodies activate these different immune effector cells, which can trigger a complex anti-tumor immune response.

Ovarian Cancer

Epithelial Cancer Epithelial Carcinoma Epithelial Ovarian Cancer Epithelial Ovarian Carcinoma Fallopian Tube Cancer Fallopian Tube Carcinoma Ovarian Cancer Ovarian Carcinoma Ovarian Epithelial Cancer Ovarian Epithelial Carcinoma Peritoneal Cancer Peritoneal Carcinoma Advanced Epithelial Ovarian Cancer

null

1

arm 1: None

[ 0 ]

1

[ 0 ]

intervention 1: Catumaxomab administered as four 3-hour, constant-rate, intraperitoneal (IP) infusions of 10, 20, 50, 150 microgram (mcg).

intervention 1: catumaxomab

12

0

NCT00377429

[ 3 ]

11

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

true

Primary Objective: 1\. To evaluate whether 5 azacytidine (5-aza)/valproic acid (VPA) or low dose ara-C produces longer event free survival time in patients age \> or = 60 years with untreated Acute Myeloid Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS) who are typically ineligible for, or not placed on, studies of new agents. Secondary Objective: 1\. To evaluate whether pre-treatment methylation/acetylation status in AML/MDS blasts predicts response to either therapy or whether the ability of the 5 azacytidine + valproic acid combination to induce demethylation or acetylation parallels response.

5-aza is a chemotherapy drug with activity in leukemia and MDS. Researchers hope that VPA will increase the effects of 5-aza. Low-dose Cytarabine (ara-C) is considered the standard of care for the treatment of leukemia and MDS in older patients not eligible for other therapies. Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have blood drawn (about 2 teaspoons) for routine tests. You will also have a bone marrow biopsy and aspiration performed. To collect a bone marrow biopsy/aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test. If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive 5-aza and VPA. Participants in the other group will receive ara-C alone. At first, there will be an equal chance of being assigned to either group. As the study goes along, however, the chance of being assigned to the treatment that has worked best so far will increase. Participants in the 5-aza and VPA group will receive 5-aza as an injection under the skin once a day for 7 days in a row. On these same 7 days, participants in this group will also take VPA by mouth twice a day or 3 times a day based on your weight. Seven (7) days is considered 1 treatment cycle. Both drugs will be taken at the same time. Cycles will be repeated every 4 to 6 weeks. Participants in the ara-C group will receive ara-c twice a day as an injection under the skin for 10 days (1 cycle). Cycles will be repeated every 4 to 6 weeks. You will be monitored with routine blood tests (about 1-2 teaspoons each time) 2-3 times a week during this study. You may receive up to 12 cycles of therapy. You may be taken off study early if the disease gets worse or intolerable side effects occur. Once you go off study, you will have standard follow-up as is required by your primary physician. This is an investigational study. 5-aza is approved by the FDA for MDS. VPA is approved by the FDA for epilepsy. Their use together in this study is experimental. Ara-C is approved for acute myelogenous leukemia. About 70 patients will take part in this study. All will be enrolled at M. D. Anderson.

Acute Myelogenous Leukemia Myelodysplastic Syndrome Leukemia

Acute Myelogenous Leukemia AML Myelodysplastic Syndrome Leukemia MDS Azacytidine 5-Azacytidine 5-aza Vidaza 5-AZC AZA-CR Ladakamycin Ara-C Cytarabine Cytosar DepoCyt Cytosine arabinosine hydrochloride Valproic Acid VPA Depakene

null

2

arm 1: 5-Azacytidine (5-Aza) 75 mg/m\^2 subcutaneously daily + Valproic Acid (VPA) 50 mg/m\^2 orally daily, each for 7 days arm 2: Low-Dose Ara-C 20 mg twice daily subcutaneously for 10 days.

[ 1, 1 ]

3

[ 0, 0, 0 ]

intervention 1: 75 mg/m\^2 daily for 7 days (days 1-7) via subcutaneous injection. intervention 2: 20 mg twice daily via subcutaneous injection for 10 days. intervention 3: 50 mg/m\^2 orally daily days 1-7.

intervention 1: 5-Azacytidine intervention 2: Ara-C intervention 3: Valproic Acid (VPA)

1

Houston | Texas | United States | -95.36327 | 29.76328

0

NCT00382590

[ 4 ]

679

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

false

This study was designed to determine the efficacy and tolerability of TREXIMET (formerly known as TREXIMA) compared to placebo for the acute treatment of probable migraine, a sub-type of migraine.

null

Migraine, Without Aura

sumatriptan succinate, naproxen sodium, parallel group, double-blind, placebo-controlled, Combination product, migrainous headache Probable migraine, a sub-type of Migraine probable migraine,

null

2

arm 1: None arm 2: None

[ 2, 0 ]

2

[ 0, 0 ]

intervention 1: sumatriptan 85mg / naproxen sodium 500mg intervention 2: Placebo to match Treximet tablets

intervention 1: sumatriptan succinate / naproxen sodium intervention 2: Placebo

70

0

NCT00387881

[ 3 ]

40

NA

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

null

In this 4-year extension study the safety, efficacy and and pharmacokinetics of deferasirox in regularly transfused pediatric patients with β-thalassemia major was assessed. Patients who successfully completed the main 1 year trial (NCT00390858) were eligible to continue in this extension trial and receive chelation therapy with deferasirox for up to 4 years.

null

Transfusional Iron Overload β-thalassemia Major Pediatric Rare Anemia

β-thalassemia major iron overload deferasirox pediatric rare anemia

null

1

arm 1: Initial dose of 10 mg/kg, dose modifications of ± 5 or 10 mg/kg were based on participant response.

[ 0 ]

1

[ 0 ]

intervention 1: Deferasirox in children from 1 to 18 years old was given orally once daily, 30 minutes prior to breakfast. An initial daily dose of 10 mg/kg was used during the 1-year core study. In this 4-year extension study dose modifications of ± 5 or 10 mg/kg were based on safety parameters and on increasing or decreasing Liver Iron Concentration (LIC), and serum ferritin. Deferasirox was available as 125 mg, 250 mg and 500 mg tablets.

intervention 1: Deferasirox

4

Lyon | N/A | France | 4.84671 | 45.74846 Cagliari | N/A | Italy | 9.11917 | 39.23054 Genova | N/A | Italy | 11.87211 | 45.21604 Torino | N/A | Italy | 11.99138 | 44.88856

0

NCT00390858

[ 4 ]

528

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

null

Primary objective: To demonstrate the efficacy of ciclesonide, compared to placebo, at 80 μg twice daily (BID) or 40 μg BID for 12 weeks in patients with persistent asthma. Secondary objective: To assess the safety and tolerability of ciclesonide.

null

Asthma

Bronchial Asthma

null

3

arm 1: double-blind arm 2: double-blind arm 3: double-blind

[ 2, 0, 0 ]

3

[ 0, 0, 0 ]

intervention 1: Ciclesonide MDI 40 µg BID over twelve weeks intervention 2: Ciclesonide MDI 80 µg BID over twelve weeks intervention 3: Placebo MDI over twelve weeks

intervention 1: Ciclesonide intervention 2: Ciclesonide intervention 3: Placebo

6

Bridgewater | New Jersey | United States | -74.64815 | 40.60079 Budapest | N/A | Hungary | 19.04045 | 47.49835 Mexico | N/A | Mexico | -98.43784 | 18.88011 Warsaw | N/A | Poland | 21.01178 | 52.22977 Moscow | N/A | Russia | 37.61556 | 55.75222 Midrand | N/A | South Africa | 28.118 | -25.976

0

NCT00392288

[ 3 ]

197

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

1FEMALE

true

The primary objective of this study was to compare the safety of dose-dense ABI-007 (Abraxane) 260 mg/m\^2 or Taxol 175 mg/m\^2 given every 2 weeks following dose-dense Adriamycin plus Cytoxan (AC) chemotherapy. Bevacizumab was administered at 10 mg/kg every 2 weeks throughout chemotherapy, and then at 15 mg/kg every 3 weeks following chemotherapy.

null

Breast Cancer

Adjuvant therapy Bevacizumab Abraxane Early stage breast cancer

null

2

arm 1: Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 260 mg/m\^2 ABI-007 (Abraxane) plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46). arm 2: Adriamycin and Cytoxan plus Bevacizumab for four cycles (weeks 1-8); 175 mg/m\^2 Taxol plus Bevacizumab for four cycles (weeks 9-16); Bevacizumab (weeks 17-46).

[ 0, 0 ]

5

[ 0, 0, 0, 0, 0 ]

intervention 1: Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) make up the chemotherapy regimen known as AC. Adriamycin 60 mg/m\^2 intravenous, plus Cytoxan 600 mg/m\^2 intravenous on Day 1 of each of four 2-week cycles (weeks 1-8). intervention 2: 260 mg/m\^2 IV on day 1 of each of four 2-week cycle, representing treatment cycles 5-8 (weeks 9-16) intervention 3: 175 mg/m\^2 intravenously (IV) on day 1 of each of four 2-week cycle, representing treatment cycles 5-8 (weeks 9-16) intervention 4: 10 mg/kg on day 1 of each of eight 2-week cycles (weeks 9-16), then 15 mg/kg on day 1 of each of ten three-week cycles (weeks 17-46). intervention 5: 6 mg subcutaneous (SC) on day 2 for each of the first four 2-week cycles (weeks 1-8). Pegfilgrastim 6 mg SC was administered on day 2 of cycles 6-8 (weeks 11-16) during taxane treatment only if necessary.

intervention 1: Adriamycin and Cytoxan (AC) intervention 2: ABI-007 intervention 3: Taxol intervention 4: Bevacizumab intervention 5: pegfilgrastim

27

0

NCT00394251

[ 4 ]

655

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

false

The purpose of this study is to evaluate the combination of alogliptin, once daily (QD), and pioglitazone in patients with type 2 diabetes mellitus who are inadequately controlled with diet and exercise alone.

There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% is type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected, placing an ever-increasing burden on families and the health care system. Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of antidiabetic medications with different mechanisms of action including insulin and insulin analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of alpha- glucosidase, analogs of glucagon-like peptide-1, and synthetic analogues of human amylin. Despite the variety of medications, many have clinically important or potentially life-threatening side effects, restricted use in many subpopulations, concerns with long-term tolerability, and challenges related to compliance due to side effects and route of administration. All of these reasons contribute to the difficulties patients have reaching the target glycosylated hemoglobin level less than 7%. SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4 enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus. Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. As the rate of newly diagnosed cases of type 2 diabetes mellitus continues to grow, so does the need for products that will provide better glycemic control and improved safety and tolerability. Alogliptin and pioglitazone have complementary actions. Alogliptin inhibits the degradation of glucagon-like peptide-1 by inhibiting the enzyme dipeptidyl peptidase IV, thus augmenting glucose-dependent insulin secretion while pioglitazone is a peripheral and hepatic insulin sensitizer. Given the complementary mechanisms of action of alogliptin (stimulates insulin secretion) and pioglitazone (enhances insulin sensitivity), the addition of combination therapy in treatment naïve type 2 diabetes patients may potentially allow the patients to reach and maintain their glycosylated hemoglobin goal more effectively. The aim of this study is to evaluate the effectiveness of the combination of alogliptin with pioglitazone in patients who are inadequately controlled on diet and exercise alone. Study participation is anticipated to be approximately 8.5 months.

Diabetes Mellitus

Glucose Metabolism Disorder Dysmetabolic Syndrome Type II Diabetes Diabetes Mellitus, Lipoatrophic Dyslipidemia Drug Therapy

null

4

arm 1: Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks. arm 2: Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks. arm 3: Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks. arm 4: Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.

[ 0, 1, 0, 1 ]

3

[ 0, 0, 0 ]

intervention 1: Alogliptin tablets. intervention 2: Pioglitazone tablets. intervention 3: Matching placebo tablets.

intervention 1: Alogliptin intervention 2: Pioglitazone intervention 3: Placebo

161

0

NCT00395512

[ 5 ]

77

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

0ALL

null

Chronic sinusitis is reported to be one of the most widespread disorders in the United States. It can be caused by a variety of reasons such as allergy, infection and/or defects in T-cells which help regulate immune function. Medication and other costs related to treatment of nasal and sinus infections are estimated to be more than $60 million annually putting a considerable strain on the economy of health care. Probiotics are live microorganisms that are normally present in the gut of a healthy individual. They are also known as "friendly bacteria" and have been used to help maintain the normal functioning of the immune system. They are safe and are commercially available in the form of yoghurt, sachets, chewable tablets or flavored capsules. Since a number of nasal and sinus disorders are related to allergy and improper functioning of the immune system, we hypothesize that regular use of probiotics may help improve chronic nasal and sinus symptoms by boosting immune responses. The project we propose is novel because it would be the first study evaluating the usefulness of probiotics for the larger population having chronic sinusitis rather than those having only allergic symptoms. We aim to assess whether regular use of probiotics will help improve symptoms of chronic sinusitis and will have a greater effect than placebo in this regard.

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. They are a part of the normal gastrointestinal flora and have safely been used to boost immune responses in patients with perennial and seasonal allergic rhinitis. Their exact mechanism of benefit is unknown but they primarily help to regulate T-cell function which is important in maintaining immune tolerance. Chronic rhinosinusitis is widely prevalent and affects nearly 16 million people in the US alone each year. It puts a strain on the health resources of the nation in terms of costs related to medications and surgery. Chronic rhinosinusitis can be caused by a variety of reasons including allergy/hypersensitivity, infection, nasal anatomical variations and T-cell regulatory dysfunction. We hypothesize that regular use of probiotics in patients with chronic rhinosinusitis will result in substantial improvement in their symptoms by boosting their immunity and may also help decrease their medication usage. Our study will be a double-blinded, randomized, control trial. We hope to recruit 100 patients from the University Otolaryngology and Allergy Clinics. Fifty patients will be randomized to the treatment (active) arm and 50 patients to the placebo arm. Subjects will be followed for 2 months during their period of participation in the study. The main aim of our study is to determine whether regular use of probiotics in patients with chronic rhinosinusitis helps improve their quality of life. Our main outcome of interest is a change in the mean score of the Sino-Nasal Outcome Test (SNOT-20) form in the treatment group and a greater change in the mean score of the SNOT-20 in the treatment arm as compared to the placebo arm. If probiotics are found to be effective, they may be used as a cost-effective, adjunctive therapy for patients with chronic rhinosinusitis.

Chronic Rhinosinusitis

null

2

arm 1: Placebo pills on same schedule as active intervention. arm 2: L. rhamnosus R0011 strain

[ 2, 1 ]

2

[ 0, 10 ]

intervention 1: 500 million active cells of L rhamnosus R0011 strain per tablet bid for 4 weeks intervention 2: Placebo pill

intervention 1: probiotic containing L.rhamnosus R0011 strain intervention 2: Placebo

0

null

0

NCT00396162

[ 4 ]

316

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

false

The purpose of this study is to measure the effectiveness and assess the safety of two dosages of the antipsychotic paliperidone extended-release (ER) in patients who are experiencing an acute episode of schizoaffective disorder.

Schizophrenia and schizoaffective disorder are closely related in terms of symptoms, coexisting conditions, and genetic risk. In previous studies in patients with schizophrenia, treatment with paliperidone extended-release (ER) improved psychotic symptoms, as well as mood symptoms evaluated by anxiety/depression and hostility/excitement Positive and Negative Symptoms of Schizophrenia (PANSS) factor scores. Therefore, paliperidone ER may also be effective in treating symptoms of schizoaffective disorder. Paliperidone's limited potential for drug-drug interaction is particularly important in this patient population, in which multiple drug therapy is relatively common. This multicenter, double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), randomized (patients are assigned different treatments based on chance), placebo-controlled, parallel-group study is designed to examine the effectiveness and safety of paliperidone ER in adult patients with schizoaffective disorder who are experiencing an acute episode of this disorder. Patients in the study will be randomly assigned to 1 of 3 groups to receive 6 weeks of oral treatment with 1 of 2 dosages of paliperidone ER or placebo. The primary efficacy outcome will be the change from baseline to Week 6, or the last post-randomization assessment during double-blind treatment (endpoint), in the PANSS total score. Safety will be assessed by monitoring adverse events, clinical laboratory testing, pregnancy testing, vital signs measurements, physical examination, administration of a 12-lead ECG, movement disorders side effect scales, and the InterSePT Scale for Suicidal Thinking. Patients may also choose to participate in a pharmacogenomic (DNA) analysis. The primary study hypotheses are that at least one of the two dosages of paliperidone ER is better than placebo on the change from baseline in the PANSS total score in acutely ill patients with schizoaffective disorder at the end of 6 weeks of treatment. Patients will receive study drug by mouth for a total of 43 days. Beginning on Day 1, patients will take either placebo or 1 of 2 doses of paliperidone: 6 mg/day (low randomized dosage) or 12 mg/day (high randomized dosage). During the first 2 weeks, dosages may be adjusted.

Schizoaffective Disorder Psychotic Disorder

Schizoaffective Disorder antipsychotic paliperidone placebo

null

3

arm 1: Paliperidone ER 12mg/day paliperidone er for 6 weeks arm 2: Paliperidone ER 6mg/day paliperidone er for 6 weeks arm 3: Placebo Placebo for 6 weeks

[ 0, 0, 2 ]

3

[ 0, 0, 0 ]

intervention 1: 6mg/day paliperidone er for 6 weeks intervention 2: 12mg/day paliperidone er for 6 weeks intervention 3: Placebo for 6 weeks

intervention 1: Paliperidone ER intervention 2: Paliperidone ER intervention 3: Placebo

0

null

0

NCT00397033

[ 5 ]

15

NON_RANDOMIZED

SINGLE_GROUP

0TREATMENT

0NONE

false

0ALL

false

We hypothesize that duloxetine treatment will be associated with improvement in symptoms of IBS, particularly abdominal pain, in individuals without comorbid major depressive disorder. During this 12-week, open-label, outpatient study, male and female subjects between the ages of 18 and 65 years who have been diagnosed with irritable bowel syndrome (IBS) will be treated with open-label duloxetine.

IBS is a chronic gastrointestinal disorder characterized by abdominal pain, altered bowel habits, and abdominal bloating for which no organic cause can be determined. Duloxetine has demonstrated efficacy in the treatment of depression as well as in several pain syndromes including diabetic peripheral neuropathy and fibromyalgia. We hypothesize that it will be a safe and efficacious treatment for the symptoms of IBS, in particular abdominal pain. We plan to study 15 male and female subjects between the ages of 18 and 65 years who have had gastrointestinal symptoms at least 2 days/week for greater than six months and who have been diagnosed with IBS by a physician. During the 12-week study, subjects will receive open-label duloxetine titrated up to 60mg/day. Subjects will be asked to complete a total of ten study visits during the 12-week study period. All study visits will be conducted at McLean Hospital.

Irritable Bowel Syndrome

IBS irritable bowel syndrome irritable bowel

null

1

arm 1: 12-week, open-label trial of duloxetine in subjects with IBS.

[ 5 ]

1

[ 0 ]

intervention 1: 30mg oral duloxetine per day for one week, titrated up to 60mg per day at day 8, concluded by a one week taper period of 4 days of 30mg pills at the conclusion of the study, followed by 3 days on no medication (4+3 days=1 week), concluded with a post-taper follow-up appointment with a study physician.

intervention 1: duloxetine

1

Belmont | Massachusetts | United States | -71.17867 | 42.39593

0

NCT00401258

[ 3 ]

159

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

false

This trial investigated the efficacy and safety of 400mg/day of lacosamide as compared to placebo in reducing the signs and symptoms of fibromyalgia syndrome.

This was a proof-of-concept study and not powered for statistical comparisons. The trial consisted of a 4-week Titration Phase, an 8-week Maintenance Phase, a 1-week Taper Phase, and a 2-week Safety Follow-Up Phase. If subjects met the eligibility criteria, they were randomized to receive either lacosamide 400mg/day or placebo during the Maintenance Phase. Subjects assigned to lacosamide were titrated from 100mg/day to 400mg/day at weekly intervals of 100mg. All subjects who completed the 4-week Titration Phase entered an 8-week Maintenance Phase. No dose adjustment was allowed during the Maintenance Phase. The Treatment Phase was defined as the combined Titration and Maintenance Phases.

Fibromyalgia Syndrome

Fibromyalgia Syndrome Lacosamide Vimpat Harkoseride

null

2

arm 1: None arm 2: Lacosamide Tablet 400mg daily

[ 2, 0 ]

2

[ 0, 10 ]

intervention 1: Tablet 400mg daily (200mg twice daily) during 8-week maintenance phase following 4-week titration phase starting at 100mg/day and increasing to 400mg/day at weekly intervals of 100mg intervention 2: Matching placebo tablet administered twice daily

intervention 1: Lacosamide intervention 2: Placebo

25

0

NCT00401830

[ 3 ]

310

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

false

The primary purpose of this study is to evaluate the efficacy and safety of administration of linaclotide acetate in patients with chronic constipation.

null

Chronic Constipation

Constipation Chronic Constipation Microbia linaclotide linaclotide acetate MD-1100

null

5

arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None

[ 1, 1, 1, 1, 2 ]

2

[ 0, 0 ]

intervention 1: oral, once daily. intervention 2: oral, once daily

intervention 1: linaclotide acetate intervention 2: Matching placebo

60

0

NCT00402337

[ 4 ]

44

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

null

This exploratory study is designed to determine the early viral kinetic profile during treatment with telbivudine or entecavir at multiple time points over 12 weeks.

null

Hepatitis B Chronic Hepatitis B

HBeAg-positive, chronic hepatitis B telbivudine entecavir viral kinetics

null

2

arm 1: None arm 2: None

[ 0, 1 ]

2

[ 0, 0 ]

intervention 1: Entecavir 0.5 mg once daily for 12 weeks. intervention 2: Telbivudine 600 mg once daily for 12 weeks.

intervention 1: Entecavir intervention 2: Telbivudine

8

Bucheon,Kyunggi | N/A | South Korea | 126.78306 | 37.49889 Busan | N/A | South Korea | 129.03004 | 35.10168 Daegu | N/A | South Korea | 128.59111 | 35.87028 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

0

NCT00412529

[ 3 ]

70

RANDOMIZED

PARALLEL

0TREATMENT

2DOUBLE

false

0ALL

true

To evaluate the efficacy, safety and tolerability of CP-195543 and celecoxib dual therapy in subjects with rheumatoid arthritis

Trial enrollment was prematurely discontinued on December 3, 2007. The results of an interim efficacy and safety analysis demonstrated an overall poor tolerability profile and high discontinuation rate when dual therapy with CP-195543 and Celecoxib was administered. The decision to discontinue further enrollment in the trial was not based on any efficacy or serious safety concerns. Previously enrolled study participants continued in the study and the trial completed on February 27, 2008.

Arthritis, Rheumatoid

null

3

arm 1: Celecoxib with placebo therapy. arm 2: Background Methotrexate taken in both CP-195,543/Celecoxib and Celecoxib only arms. arm 3: CP-195,543 and Celecoxib dual therapy.

[ 1, 5, 0 ]

3

[ 0, 0, 0 ]

intervention 1: CP-195543 is a potent and specific antagonist of the leukotriene B4 (LTB4) receptor. intervention 2: Celecoxib is a nonsteroidal anit-inflammatory drug (NSAID) marketed worldwide (in the United States \[US\] as Celeberex) and approved for the relief of signs and symptoms of osteoarthritis. intervention 3: Methotrexate is a folate analogue that, based on it efficacy and safety in RA, is commonly used as frontline DMARD treatment in patients with moderate to severe disease who do not respond to NSAIDs alone.

intervention 1: CP-195,543 intervention 2: celecoxib intervention 3: Methotrexate

39

0

NCT00424294

[ 4 ]

262

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

null

This study was designed to evaluate the safety and tolerability of switching from donepezil to an initial dose of 5cm\^2 rivastigmine patch formulation in patients with probable Alzheimer's Disease (MMSE 10-24). The study included a 5-week, open-label, randomized period followed by a 20-week open-label extension period. Patients were randomized to either an immediate switch from donepezil to rivastigmine patch formulation or to a switch to rivastigmine patch formulation following a 7-day withdrawal period.

null

Alzheimer's Disease

Dementia, Alzheimer's, Rivastigmine, donepezil

null

2

arm 1: Patients randomized to the immediate switch group continued treatment with donepezil through the evening prior to Day 8 of the study. On Day 8, all patients began open-label treatment with 5 cm\^2 rivastigmine patch formulation. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study. arm 2: Patients randomized to the delayed switch group were switched to 5 cm\^2 rivastigmine patch formulation on Day 8, following a 7-day withdrawal period from donepezil. A new patch was applied daily for 4 weeks. Patients who completed the core phase had the option of entering the extension phase, in which they received open-label treatment with rivastigmine patch formulation for an additional 20 weeks. In the absence of any dose-limiting adverse events (AEs), the dose was increased to 10 cm\^2 patch, and it remained the same through Week 25. Patients who experienced dose-limiting AEs had their dose reduced to 5 cm\^2 patch and continued on their best tolerated dose for the remainder of the study.

[ 0, 0 ]

2

[ 0, 0 ]

intervention 1: Rivastigmine 5 cm\^2 patch size, loaded with 9 mg and providing 4.6 mg rivastigmine per 24 hours. intervention 2: Rivastigmine 10 cm\^2 patch size loaded with 18 mg and providing 9.5 mg rivastigmine per 24 hours.

intervention 1: Rivastigmine 5 cm^2 transdermal patch intervention 2: Rivastigmine 10 cm^2 transdermal patch

23

0

NCT00428389

[ 5 ]

132

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

0ALL

false

The purpose of this study is to compare the safety and efficacy of solifenacin with oxybutynin immediate-release (IR) for the treatment of overactive bladder (OAB).

This study is a prospective randomized, double-blind, double-dummy, multicentre, 2-arm (1 Active, Active Control) comparative parallel group study to compare the safety and efficacy of solifenacin with oxybutynin immediate-release (IR) for the treatment of overactive bladder (OAB).

Overactive Bladder

Solifenacin succinate Oxybutynin immediate release Xerostomia Overactive bladder

null

2

arm 1: Solifenacin succinate: 5 mg tablets, taken orally, once daily arm 2: Oxybutynin Immediate Release: 5 mg capsules, taken orally, 3 times a day

[ 0, 1 ]

2

[ 0, 0 ]

intervention 1: Oral intervention 2: Oral

intervention 1: solifenacin intervention 2: oxybutynin immediate release

12

0

NCT00431041

[ 2 ]

30

RANDOMIZED

FACTORIAL

0TREATMENT

2DOUBLE

true

0ALL

true

The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of a single, daily, oral dose of ST-246 (either 250, 400 or 800mg) administered for 21 days to 30 healthy, fed volunteers.

This was a double-blind, placebo-controlled, dose-escalating, multiple-dose study of orally administered ST-246 to 30 healthy volunteers ages 18-50 years, randomized to receive either active drug (8 subjects) or placebo (2 subjects) in 1 of 3 dosing groups (250, 400 or 800mg groups). Each dose group of 10 was divided into two cohorts of 5 subjects (4 active and 1 placebo). The first cohort was dosed approximately 4-8 weeks before the second cohort of each dose group. Dose groups completed the study treatment approximately 5 weeks prior to the start of the following dose group. Study procedures included several overnight stays, medical history/exam, laboratory testing done by blood draw, and electrocardiograms.

Healthy

Healthy Volunteers

null

2

arm 1: 250 mg, 400 mg or 800 mg of ST-246 given once daily for 21 days arm 2: Placebo to match ST-246

[ 0, 2 ]

2

[ 0, 0 ]

intervention 1: 250 mg, 400 mg or 800 mg capsules given once daily for 21 days intervention 2: Capsules to match experimental drug

intervention 1: ST-246 intervention 2: Placebo

1

Orlando | Florida | United States | -81.37924 | 28.53834

0

NCT00431951

[ 4 ]

219

RANDOMIZED

CROSSOVER

0TREATMENT

1SINGLE

false

0ALL

false

The scalp is one of the most common affected sites in psoriatic patients as 79% of them have scalp involvement.It has also a psychological aspect with 31% of patients with scalp psoriasis indicating distress. Topical agents remain the mainstay of treatment for scalp psoriasis. However, they are not always ideal because they might be inconvenient and messy to use, stain or damage hair. The test shampoo, Clobetasol propionate Shampoo 0.05% (marketed in the USA under the tradename of Clobex®) was developed to provide the strongest available corticosteroid as a short-contact therapy in order to improve the chances of it being effective and reduce the potential for traditional side-effects. The objective of this study is to compare subject's overall preference between Clobetasol propionate shampoo 0.05% and three other topical corticosteroids in the treatment of moderate to severe scalp psoriasis.

This study will be a multi-centre, investigator blinded, randomized, cross-over, intra-individual comparison in three parallel groups. In each parallel group, Clobetasol propionate shampoo, 0.05% will be compared to one of the three chosen competitors, following a cross-over design.

Scalp Psoriasis

1 Galderma, 2 Scalp Psoriasis 3 Subject preference 4 Clobetasol propionate 5 Shampoo

null

6

arm 1: Clobetasol propionate Shampoo: * Dose or Concentration: Clobetasol propionate 0.05% shampoo * Mode and Frequency of Administration: Topical Once daily to the dry scalp, to be lathered and rinsed after 15 minutes * Duration of Treatment: 4 weeks as a maximum Wash-out up to 8 weeks Corticosteroid 1: * Dose or Concentration: Corticosteroid 1 Foam * Mode and Frequency of Administration:Twice daily, a "golf-ball" sized amount to be massaged into the affected area of the scalp * Duration of Treatment: 4 weeks as a maximum arm 2: Clobetasol propionate Shampoo: * Dose or Concentration: Clobetasol propionate 0.05% shampoo * Mode and Frequency of Administration: Topical Once daily to the dry scalp, to be lathered and rinsed after 15 minutes * Duration of Treatment: 4 weeks as a maximum Corticosteroid 2: * Dose or Concentration: Corticosteroid 2 Lotion * Mode and Frequency of Administration: Twice daily, a thin film to be applied to the affected area of the scalp and massaged gently and thoroughly into the skin * Duration of Treatment: 4 weeks as a maximum arm 3: Clobetasol propionate Shampoo: * Dose or Concentration: Clobetasol propionate 0.05% shampoo * Mode and Frequency of Administration: Topical Once daily to the dry scalp, to be lathered and rinsed after 15 minutes * Duration of Treatment: 4 weeks as a maximum Corticosteroid 3: * Dose or Concentration: Corticosteroid 3 Scalp application * Mode and Frequency of Administration: Twice daily, a thin film to be applied into the affected area of the dry scalp and rubbed gently into the scalp * Duration of Treatment: 4 weeks as a maximum arm 4: Clobetasol propionate Shampoo: * Dose or Concentration: Clobetasol propionate 0.05% shampoo * Mode and Frequency of Administration: Topical Once daily to the dry scalp, to be lathered and rinsed after 15 minutes * Duration of Treatment: 4 weeks as a maximum Corticosteroid 1: * Dose or Concentration: Corticosteroid 1 Foam * Mode and Frequency of Administration:Twice daily, a "golf-ball" sized amount to be massaged into the affected area of the scalp * Duration of Treatment: 4 weeks as a maximum arm 5: Clobetasol propionate Shampoo: * Dose or Concentration: Clobetasol propionate 0.05% shampoo * Mode and Frequency of Administration: Topical Once daily to the dry scalp, to be lathered and rinsed after 15 minutes * Duration of Treatment: 4 weeks as a maximum Corticosteroid 2: * Dose or Concentration: Corticosteroid 2 Lotion * Mode and Frequency of Administration: Twice daily, a thin film to be applied to the affected area of the scalp and massaged gently and thoroughly into the skin * Duration of Treatment: 4 weeks as a maximum arm 6: Clobetasol propionate Shampoo: * Dose or Concentration: Clobetasol propionate 0.05% shampoo * Mode and Frequency of Administration: Topical Once daily to the dry scalp, to be lathered and rinsed after 15 minutes * Duration of Treatment: 4 weeks as a maximum Corticosteroid 3: * Dose or Concentration: Corticosteroid 3 Scalp application * Mode and Frequency of Administration: Twice daily, a thin film to be applied into the affected area of the dry scalp and rubbed gently into the scalp * Duration of Treatment: 4 weeks as a maximum

[ 1, 1, 1, 1, 1, 1 ]

6

[ 0, 0, 0, 0, 0, 0 ]

intervention 1: Twice daily application intervention 2: Twice daily application intervention 3: Twice daily application intervention 4: Twice daily application intervention 5: Twice daily application intervention 6: Twice daily application

intervention 1: C. propionate - Corticosteroid 1 intervention 2: C. propionate- Corticosteroid 2 intervention 3: C. propionate -Corticosteroid 3 intervention 4: Corticosteroid 1- C. propionate intervention 5: Corticosteroid 2 - C. propionate intervention 6: Corticosteroid 3 - C. propionate

1

Modena | N/A | Italy | 10.92539 | 44.64783

0

NCT00438399

[ 4 ]

375

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

true

The purpose of this study is to demonstrate that once weekly and once every-2-weeks treatment with epoetin alfa, in patients with anemia associated with chronic kidney disease, is not less effective than the approved treatment with epoetin alfa that is given 3 times weekly with respect to changes in hemoglobin.

This is a open-label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), multicenter study designed to show that 2 alternative dosing regimens, once weekly and once every-2-weeks (given at doses equivalent to 50 IU/kg 3 times a week) are not inferior to the 3-times-weekly dosing regimen. Approximately 375 patients with anemia will be enrolled in this study. Patients will be randomly assigned to receive epoetin alfa by subcutaneous (SC) injection according to one of the following 3 regimens: 3 times weekly (Group 1), once weekly (Group 2), or once every 2 weeks (Group 3) for 22 weeks. Thereafter, patients in Group 1 will be switched to the once-weekly dosing regimen for an additional 22 weeks, and patients in Groups 2 and 3 will continue their current treatment for an additional 22 weeks. The total duration of the open-label treatment phase is 44 weeks which will include initiation and maintenance treatment periods (with the goal of increasing, then maintaining, the hemoglobin level between 11.0 and 11.9 g/dL inclusive) and a safety period (to assess longer exposure to epoetin alfa treatment and any period of hemoglobin instability during the transition from 3-times-weekly to once-weekly dosing). Starting doses of epoetin alfa in the 3-times-weekly, once-weekly, and every-2-weeks groups will be 50 IU/kg, 10,000 IU, and 20,000 IU, respectively; thereafter adjusted according to weekly hemoglobin concentrations. Safety evaluations will include assessment of adverse events, laboratory tests, physical examinations, and vital signs.

Anemia

Anemia Chronic Kidney disease Kidney disease Epoetin alfa Procrit

null

3

arm 1: Participants will be administered with epoetin alfa 3 times weekly for 22 weeks (initial subcutaneous (SC) dose 50 IU/kg), then once weekly, for 22 weeks (initial SC dose 10,000 IU) arm 2: Participants will be administered with epoetin alfa once weekly for 44 weeks (initial subcutaneous dose 10,000 IU). arm 3: Participants will be administered with epoetin alfa once every 2 weeks for 44 weeks (initial subcutaneous dose 20,000 IU).

[ 0, 0, 0 ]

3

[ 0, 0, 0 ]

intervention 1: Epoetin alfa will be administered as a SC injections at initial dose of 50 IU/kg (3 times weekly for 22 weeks) and at initial dose of 10000 IU (once weekly for 22 weeks) intervention 2: Epoetin alfa will be administered as a SC injection at initial dose of 10000 IU (once weekly for 44 weeks). intervention 3: Epoetin alfa will be administered as a SC injection at initial dose of 20000 IU (once every 2 weeks for 44 weeks).

intervention 1: Epoetin alfa 3 times weekly /once weekly intervention 2: Epoetin alfa once weekly intervention 3: Epoetin alfa once every two weeks

62

0

NCT00440557

[ 3 ]

213

RANDOMIZED

PARALLEL

0TREATMENT

3TRIPLE

false

1FEMALE

null

This study will explore the safety and effectiveness of different doses of AGN 203818 in relieving Irritable Bowel Syndrome pain. The study is being conducted in 2 parts. Part A enrolled 213 pts dosed with either 3, 20, 60 mg AGN 203818 or placebo over 4 week treatment duration. Part B will enroll 320 pts and dose with either 60, 100, 160 mg BID AGN 203818 or placebo over 12 week treatment duration.

null

Irritable Bowel Syndrome

null

4

arm 1: Part A: AGN 203818 3mg capsule every 12 hours for 4 weeks arm 2: Part A: AGN 203818 20mg capsule every 12 hours for 4 weeks arm 3: Part A: AGN 203818 60mg capsule every 12 hours for 4 weeks arm 4: Part A: Placebo capsule every 12 hours for 4 weeks

[ 0, 0, 0, 2 ]

4

[ 0, 0, 0, 0 ]

intervention 1: Part A: 3 mg AGN203818 capsule every 12 hours for 4 weeks intervention 2: Part A: 20 mg AGN203818 capsule every 12 hours for 4 weeks intervention 3: Part A: 60 mg AGN203818 capsule every 12 hours for 4 weeks intervention 4: Part A: placebo capsule every 12 hours for 4 weeks

intervention 1: AGN 203818 intervention 2: AGN 203818 intervention 3: AGN 203818 intervention 4: placebo

1

Orange | California | United States | -117.85311 | 33.78779

0

NCT00441766

[ 3 ]

35

RANDOMIZED

PARALLEL

0TREATMENT

4QUADRUPLE

false

0ALL

false

The purpose of this study is to evaluate the safety and efficacy of asimadoline in patients who have undergone a laparoscopic segmental colectomy and determine whether it reduces the time to recovery of bowel function compared to placebo.

This randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy and tolerability of two dose levels of asimadoline on the duration of post-operative ileus in subjects undergoing laparoscopic or hand-assisted laparoscopic colon resections. Subjects meeting entry criteria were randomized in a 1:1:1 ratio to receive either asimadoline 1.0 mg, asimadoline 3.0 mg or a placebo. One hundred and fourteen subjects were planned, and in the event that a subject was converted from a laparoscopic surgery to an open surgery (laparotomy), that subject would be discontinued from the trial and followed for safety only. The protocol allowed subjects converted to open procedures to be replaced. The first dose was administered approximately 90 minutes pre-operatively, and subsequent dosing was b.i.d. for up to 10 post-operative doses. Subjects were dosed with study drug only while in the hospital. After discharge, they were followed for an additional 28 days. Total study duration for each patient was approximately 5 to 6 weeks.

Post-Operative Ileus

null

3

arm 1: None arm 2: Asimadoline 1.0 mg b.i.d. arm 3: Asimadoline 3.0 mg b.i.d.

[ 2, 1, 1 ]

2

[ 0, 0 ]

intervention 1: Asimadoline was provided in coated tablets of 1.0 mg strength. Subjects were given 3 tablets of study drug 90 minutes prior to their operation and then 3 tablets b.i.d. for up to 10 post-operative doses. Subjects randomized to receive 3.0 mg of asimadoline received three 1.0 mg asimadoline tablets at each scheduled dose, while those randomized to receive 1.0 mg of asimadoline received two placebo tablets and one 1.0 mg asimadoline tablet at each scheduled dose. intervention 2: Placebo was provided in coated tablets identical in appearance to asimadoline tablets. Subjects were given 3 tablets of placebo 90 minutes prior to their operation and then 3 placebo tablets b.i.d. for up to 10 post-operative doses.

intervention 1: Asimadoline intervention 2: Placebo

4

0

NCT00443040

[ 4 ]

111

RANDOMIZED

PARALLEL

0TREATMENT

0NONE

false

0ALL

null

This study will assess the efficacy and safety of methoxy polyethylene glycol-epoetin beta (Mircera) in the maintenance of hemoglobin levels in patients who have previously received treatment with epoetin alfa or darbepoetin alfa, and who are transitioning from chronic kidney disease stage 4 through dialysis. Patients will be randomized either to receive Mircera or to remain on their existing therapy; the initial monthly dose of subcutaneous (sc) Mircera (120-360 micrograms) will be based on the average weekly dose of epoetin alfa or darbepoetin alfa administered in the week preceding the switch to Mircera. At the initiation of dialysis, patients in the Mircera group will receive monthly intravenous (iv) Mircera at a starting dose based on their previous (sc) dose, and those in the control group will receive weekly (iv) epoetin alfa. The anticipated time on study treatment is 1-2 years, and the target sample size is 500+ individuals.

null

Anemia

null

3

arm 1: 120-360 micrograms methoxy polyethylene glycol-epoetin beta subcutaneous (sc) monthly starting dose, for a minimum of 5 months to a maximum of 18 months. Dosage was adjusted to maintain a hemoglobin target range of ≥10 g/dL to ≤12 g/dL. arm 2: Patients randomized to the reference arm continued to receive their standard of care dose and regimen of epoetin alfa subcutaneous once per week for a minimum of 5 months to a maximum of 18 months. Subcutaneous injections were to be administered in the same part of the body (ie, thigh, abdomen or arm) throughout the study. Dosage was adjusted to maintain a hemoglobin target range of ≥10 g/dL to ≤12 g/dL. arm 3: Patients randomized to the reference arm continued to receive their standard of care dose and regimen of darbepoetin subcutaneous once every two weeks for a minimum of 5 months and a maximum of 18 months. Subcutaneous injections were to be administered in the same part of the body (ie, thigh, abdomen or arm) throughout the study. Dosage was adjusted to maintain a hemoglobin target range of ≥10 g/dL to ≤12 g/dL.

[ 0, 1, 1 ]

3

[ 0, 0, 0 ]

intervention 1: Methoxy polyethylene glycol-epoetin beta was provided as a sterile single-use injectable solution in a 1-mL prefilled syringe containing 0.3 mL or 0.6 mL solution. The methoxy polyethylene glycol-epoetin beta injectable solution was formulated in sodium phosphate, sodium sulfate, mannitol, methionine and poloxamer 188, pH 6.2 and did not contain any preservative. Participants received methoxy polyethylene glycol-epoetin beta subcutaneous once a month. intervention 2: Standard of care as prescribed, per individual participant, subcutaneous once per week. Subcutaneous injections were to be administered in the same part of the body (ie, thigh, abdomen or arm) throughout the study. intervention 3: Standard of care as prescribed, per individual participant, darbepoetin alfa subcutaneous once every two weeks. Subcutaneous injections were to be administered in the same part of the body (ie, thigh,abdomen or arm) throughout the study.

intervention 1: methoxy polyethylene glycol-epoetin beta intervention 2: epoetin alfa intervention 3: darbepoetin alfa

78

0

NCT00454246