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Study design | SUSTAIN-3, an ongoing phase 3, open-label, multicenter (SUSTAIN-3 has a 4-week induction phase (if applicable) and an optimization/maintenance phase of variable duration. Participants in 1 of 6 phase 3, “parent” studies of esketamine and for whom benefit versus risk was favorable were enrolled into either the 4-week in... | PMC10267177 | ||
Study population | TRD, depression | The eligibility criteria of each parent study are reported elsewhere [10–14; clinical trials.gov: ID NCT03434041]. In brief, each parent study enrolled adults (≥18 years) who met the definition of TRD (i.e., non-response to an adequate trial of at least 2 antidepressants in the current episode of depression, one of whi... | PMC10267177 | |
Study drug | depression | In the induction phase, participants self-administered (under medical supervision) esketamine (28 mg [starting dose age ≥65 years], 56 mg, or 84 mg) as a flexible dose, twice-weekly therapy for 4 weeks. In the optimization/maintenance phase, participants received interval dosing of esketamine individualized to the seve... | PMC10267177 | |
Evaluations of safety and efficacy | PMC10267177 | |||
Safety | ADVERSE EVENTS, EVENTS, CYSTITIS | Treatment-emergent adverse events, including events of special interest (i.e., renal disorder/interstitial cystitis, hepatic) were monitored, and other safety assessments (i.e., hematology and serum chemistry, urinalysis, physical examination, pulse oximetry, vital signs, electrocardiogram, and Columbia-Suicide Severit... | PMC10267177 | |
Efficacy | Depression, disability, depressive illness | SHEEHAN | Montgomery–Åsberg Depression Rating Scale (MADRS) assessments [Participants rated the impact of the study treatments on socio-occupational disability using the Sheehan Disability Scale [Investigators rated severity of depressive illness using the CGI-S [ | PMC10267177 |
Statistical methods | depressive symptoms | ADVERSE EVENTS, EVENTS, REMISSION | The number (percentage) of participants with adverse events, including events of clinical interest, serious adverse events, and adverse events leading to premature discontinuation of study drug were summarized by preferred term. Descriptive statistics were provided for other safety parameters.Descriptive statistics and... | PMC10267177 |
Results | TRD | A total of 1148 adult patients with TRD were enrolled into SUSTAIN-3. Overall, 458 participants were enrolled into the induction phase, 38 (8.3%) of whom discontinued and 420 (91.7%) continued to the optimization/maintenance phase. In addition, 690 other participants were enrolled directly into the optimization/mainten... | PMC10267177 | |
Safety | PMC10267177 | |||
Dissociation | ADVERSE EVENTS, EVENTS | Dissociation included reports of perceptual disturbances where sounds, visual stimuli, and proprioception seemed exaggerated or altered, or by a sense of derealization or depersonalization. Overall, dissociation was reported in 24.4% of participants. Although no treatment for dissociation was recommended or specified i... | PMC10267177 | |
Sedation | ADVERSE EVENTS, EVENTS, RESPIRATORY DEPRESSION, ADVERSE EVENT | Sedation was reported as an adverse event in 7.8% of participants. The majority (99.4%, 1073/1079) of sedation events occurred on a dosing day and resolved the same day. Five (0.4%) participants had 1 or more sedation events that did not resolve on the day of dosing. Sedation led to esketamine dose reduction for 1 of t... | PMC10267177 | |
Increased blood pressure | ADVERSE EVENT | The greatest mean (SD) change in systolic and diastolic blood pressure (BP) from predose values were +9.3 (12.01) mmHg at day 15 and +6.1 (7.84) mmHg at day 25, respectively, in the induction phase and +10.2 (9.25) mmHg at week 184 and +6.0 (6.36) mmHg at week 184, respectively, in the optimization/maintenance phase, a... | PMC10267177 | |
Adverse events of clinical interest | renal disorder, urinary incontinence, cholelithiasis, nephrolithiasis, dysuria, UTI, hematuria, pollakiuria, interstitial/ulcerative cystitis, hepatic adverse | CHOLECYSTITIS, URINARY TRACT INFECTIONS, RENAL DISORDER, ADVERSE EVENTS, EVENT, URINARY INCONTINENCE, CHOLELITHIASIS, NEPHROLITHIASIS, HEMATURIA, UTI, EVENTS | No case of treatment-related interstitial/ulcerative cystitis was identified. Urinary tract infections (UTI) were reported in 153 (13.3%) participants, 65 of whom had more than one episode of UTI (63 of 65 were female, mean age 53.7 years). Other adverse events (incidence ≥1%) related to a renal disorder included dysur... | PMC10267177 |
Discharge readiness | At the timepoints assessed, >89% of participants were ready to be discharged from clinic by 1.5 h post dosing. | PMC10267177 | ||
Cognitive effects | Group mean performance on cognitive tests (Cogstate and HVLTR) from baseline through week 160 indicated that cognitive performance generally remained stable. There was no evidence of decline in cognition associated with long-term treatment among participants <65 years old from baseline to week 160 (Table | PMC10267177 | ||
Suicidal ideation and behavior | TRD, illness, ideation | ADVERSE EVENTS, EVENT | Overall, 5.6% of participants experienced 1 or more adverse events potentially related to suicidality. Of these, one participant died by suicide. This individual was a 48-year-old male who did not respond to esketamine (MADRS total score was 35 at baseline and 41 and 25 on days 15 and 22, respectively). The participant... | PMC10267177 |
Efficacy | PMC10267177 | |||
Depressive symptoms | Depressive | Depressive symptoms, as assessed by MADRS total score, decreased during the induction phase (Fig. | PMC10267177 | |
Mean (±SE) Montgomery–Åsberg Depression Rating Scale Total Score (Observed Cases). | depressive symptoms | REMISSION | IND Induction, OP/MA optimization/Maintenance. Note: Responders from the induction phase of the SUSTAIN-3 study and responders from parent studies were to enter the optimization/maintenance phase. The greater variability of the mean MADRS total score at later time points likely reflects the smaller number of participan... | PMC10267177 |
Functioning and associated disability | disability | REMISSION | The mean change (SD) from baseline to endpoint in SDS total score of −6.4 (7.14) indicates an improvement in functioning and associated disability during the induction phase. By endpoint of the optimization/maintenance phase, the mean change (SD) was +0.1 (8.23), suggesting maintenance of effect. The percentage of resp... | PMC10267177 |
Discussion | TRD, ideation, psychiatric, depressive symptoms, MDD, depression, drug abuse | ADVERSE EVENTS, REMISSION, ADVERSE EVENT | Long-term safety as well as remission and response with weekly or biweekly esketamine nasal spray, combined with an oral antidepressant, is being evaluated in SUSTAIN-3, a global multicenter study of participants with TRD. The results of this study extend those of a 1-year open-label study of esketamine nasal spray for... | PMC10267177 |
Supplementary information | The online version contains supplementary material available at 10.1038/s41386-023-01577-5. | PMC10267177 | ||
Acknowledgements | The authors acknowledge Dr. Paul Maruff for his contribution to the interpretation of the cognition data. Drs. Abigail I. Nash, Qiaoyi Zhang, Tricia J. Lopena, Maju Mathews, and Jaskaran B. Singh authored posters in which early data from the SUSTAIN-3 study were presented (at the 2021 Annual Meeting of the American Soc... | PMC10267177 | ||
Author contributions | NZ and D-JF designed the study and wrote the protocol. GS helped design and conduct the study. NC and RL conducted the statistical analyses. RLM designed and supervised the cognition testing. All authors were involved in writing and/or revising the manuscript, and had final responsibility for the decision to submit for... | PMC10267177 | ||
Funding | The SUSTAIN-3 study is supported by funding from Janssen Research & Development LLC, Titusville, NJ, USA. | PMC10267177 | ||
Competing interests | Johnson & Johnson. | EMA | NZ, LC, TD, WCD, VP, D-JF, and RL are employees of Janssen Research & Development, LLC or Janssen Research & Development Belgium, and all are stockholders of Johnson & Johnson. RLM was an employee of Janssen Research & Development, LLC at the time this work was conducted. In the last 12 months. GS has provided consulti... | PMC10267177 |
References | PMC10267177 | |||
Subject terms | aphasia | People with aphasia (PWA) often present deficits in non-linguistic cognitive functions, such as executive functions, working memory, and temporal information processing (TIP), which intensify the associated speech difficulties and hinder the rehabilitation process. Therefore, training targeting non-linguistic cognitive... | PMC10462731 | |
Introduction | death, disability, Stroke | STROKE | Stroke is the second leading cause of death and disability in the worldPWA also have difficulties with temporal information processing (TIP). Some studies have demonstrated a link between TIP and language. Human speech is constrained by temporal organization in the millisecond and multisecond time domains. Millisecond ... | PMC10462731 |
Methods | PMC10462731 | |||
Participants | post-stroke, stroke, left-hemispheric stroke, head injuries, dementia, ExpG, comprehension impairment, post-stroke visual deficits, neurological or psychiatric diseases, aphasia, substance abuse | STROKE | Thirty four post-stroke patients (22 male) suffering from aphasia after their first left-hemispheric stroke (lesion age: Me = 32 weeks; min–max: 5–195 weeks) participated in the study. Participants’ ages ranged from 30 to 82 years (M ± SD: 59 ± 13 years). They were right-handed native speakers of Polish. Participants d... | PMC10462731 |
Procedure | The study was comprised of both assessment and training procedures. The assessment procedures consisted of several neuropsychological measurements evaluating speech comprehension and production, TIP, memory, and executive functions (Fig. Schema of the study. | PMC10462731 | ||
Training procedure | HAND PRESENTATION | The Overview of Dr. NeuronowskiIntroductory games to familiarise patients with the training, types of games, and sounds usedAuditory perceptionReaction speedResponse inhibitionAlertnessAuditory perception of nonverbal stimuliShort-term nonverbal auditory memorySelective attentionSustained attentionMillisecond TIP—proce... | PMC10462731 | |
Statistical analyses | To verify the distributions of the resultant data, the Shapiro–Wilk Test was used and further statistical analyses were adjusted accordingly.To verify the effects of each training type on particular cognitive functions (To examine the stability of training effects | PMC10462731 | ||
Results | PMC10462731 | |||
Pre- vs post-training comparison of cognitive functions | POSITIVE | The effect of experimental and control training was evaluated for particular tasks. The profile of changes in Difference in z scores (post-training minus pre-training) for participants in the two training groups. The z scores for both post-training and pre-training were referred to pre-training performance of all parti... | PMC10462731 | |
Speech comprehension |
Sentence comprehension: the number of correct responses Grammar comprehension: the number of correct responses Word comprehension: the difference in the number of correct responses was nonsignificant between Phoneme discrimination: the number of correct responses | PMC10462731 | ||
Speech production |
Naming: the number of correct responses Verbal fluency: the number of produced words was significantly higher (Z = − 2.626; p = 0.009) | PMC10462731 | ||
Temporal information processing | ExpG |
Temporal order judgement: TOT values in ExpG were significantly lower (Z = -2.154; p = 0.031) | PMC10462731 | |
Memory | ExpG |
Verbal short-term memory: the number of correctly reproduced sequences in ExpG was significantly higher (Z = − 2.599; p = 0.009) Spatial short-term memory: the number of correctly reproduced sequences in | PMC10462731 | |
Executive functions | Verbal working memory, ExpG |
Planning ability: the difference between the number of correctly solved trials was nonsignificant (Z = − 0.595; p = 0.552) between Verbal working memory: the number of correctly reproduced sequences in ExpG was significantly higher (Z = -2.132; p = 0.033) Spatial working memory: the number of correctly reproduced sequ... | PMC10462731 | |
Summary of results | The application of the experimental training in PWA improved all assessed functions, apart from word comprehension, spatial short-term and working memory and planning ability. On the other hand, following the control training, significant improvement was observed only in grammar comprehension and naming. All reported i... | PMC10462731 | ||
Discussion | ExpG | The present study measured the effects of the Dr. NeuronowskiSeveral cognitive functions were exercised in the experimental training, with a particular emphasis on TIP, which resulted in the lowering of participants’ temporal order thresholds (TOT), enhancement of phoneme discrimination (i.e., increased number of corre... | PMC10462731 | |
Acknowledgements | We thank Tomasz Wolak for analysis and graphical presentation of neuroanatomical data as well as Anna Bombinska for her technical assistance during the data collection phase. | PMC10462731 | ||
Author contributions | M.C. designed the study, recruited the participants, acquired, analysed, and interpreted the data, and wrote the manuscript. M.S. wrote the manuscript. A.S. conceptualised and designed the study, recruited the participants, acquired, analysed, and interpreted the data, wrote the manuscript, and is responsible for the f... | PMC10462731 | ||
Funding | POLAND | Supported by the National Science Centre (Narodowe Centrum Nauki, NCN), Poland, Grant no 2016/21/B/HS6/03775. | PMC10462731 | |
Data availability | The datasets generated and/or analysed during the current study are available from the corresponding author on request. | PMC10462731 | ||
Competing interests | AS is the co-creator of the Dr. Neuronowski | PMC10462731 | ||
References | PMC10462731 | |||
Purpose: | cancer | CANCER | These authors contributed equally to this work.While moderate-to-vigorous intensity physical activity (MVPA) is associated with various health improvements shortly after completion of exercise interventions, it remains unclear which health benefits can be expected when MVPA levels are maintained in the long term in can... | PMC10331773 |
Methods: | fatigue, anxiety, cancer, prostate, depression, Cancer | REGRESSION, CANCER, PROSTATE, CANCER | In the Physical training and Cancer (Phys-Can) RCT, 577 participants diagnosed with breast (78%), prostate (19%), or colorectal (3%) cancer were randomized to 6 months of exercise during curative cancer treatment. Accelerometer-assessed physical activity and outcome data (ie, cancer-related fatigue, health-related qual... | PMC10331773 |
Results: | fatigue | A total of 353 participants were included in the analyses. At 12-month follow-up, a higher MVPA level was significantly associated with lower fatigue in 3 domains (general fatigue [β = −.33], physical fatigue [β = −.53] and reduced activity [β = −.37]), higher cardiorespiratory fitness (β = .34) and less sedentary time... | PMC10331773 | |
Conclusion: | cancer, Cancer | CANCER, CANCER | Our results suggest that long-term physical activity is essential for improving health outcomes post-intervention in cancer survivors. Cancer survivors, including those who reach recommended MVPA levels, should be encouraged to maintain or increase MVPA post-intervention for additional health benefits. | PMC10331773 |
Trial registration: | NCT02473003 (10/10/2014) | PMC10331773 | ||
Introduction | cancer, anxiety/depression, fatigue, Cancer | CANCER, CANCER | Regular physical activity has proven safe and beneficial in cancer survivors.We recently reported the results from a 6-month exercise intervention study with a 2 × 2 factorial design, the Physical Training and Cancer randomized controlled trial (Phys-Can RCT).In the present study, we investigated MVPA in cancer survivo... | PMC10331773 |
Methods | PMC10331773 | |||
Settings and Participants | Data included in the present study were collected as part of the Phys-Can RCT, a multicentre trial (NCT02473003). | PMC10331773 | ||
Intervention | PMC10331773 | |||
Exercise program | The exercise program has been described previously in detail. | PMC10331773 | ||
Additional BCS | Additional BCS used in the Phys-Can RCT have been described previously in detail. | PMC10331773 | ||
Measures | PMC10331773 | |||
Physical activity | SWA | Two physical activity measures, MVPA level at 12-month follow-up and long-term MVPA patterns (from immediately post-intervention to 12-month follow-up) were assessed with SenseWear Armband mini (SWA) immediately post-intervention and at 12-month follow-up. The SWA is a monitor combining a tri-axial accelerometer with h... | PMC10331773 | |
Cancer-related health outcomes | fatigue, Fatigue | -20 | All cancer-related health outcomes were assessed at 12-month follow-up. Cancer-related fatigue was assessed with the Multidimensional Fatigue Inventory questionnaire (MFI-20, range 4-20), | PMC10331773 |
Statistical Analyses | cancer | REGRESSION, CANCER | Descriptive characteristics are presented as mean and standard deviation (Multiple linear regression was performed to examine the associations of (1) MVPA level at 12-month follow-up and (2) long-term MVPA patterns with each cancer-related health outcome, respectively. For the analyses with long-term MVPA patterns as i... | PMC10331773 |
Results | PMC10331773 | |||
Discussion | fatigue, ’, breast cancer, cancer, lower cancer-related fatigue | CANCER, BREAST CANCER | In the present study, we investigated MVPA in cancer survivors who previously participated in an exercise intervention during curative cancer treatment. The aims were to assess the associations of (1) MVPA level at 12-months follow-up and (2) long-term MVPA patterns (from immediately post-intervention to 12-month follo... | PMC10331773 |
Conclusion | cancer, Cancer | CANCER, CANCER | Our results suggest that long-term physical activity is essential for improving health outcomes post-intervention in cancer survivors, even among those with high MVPA levels. Cancer survivors, including those who reach recommended MVPA levels, should therefore be encouraged to maintain or increase MVPA post-interventio... | PMC10331773 |
Supplemental Material | PMC10331773 | |||
sj-docx-1-ict-10.1177_15347354231178869 – Supplemental material for The Role of Long-Term Physical Activity in Relation to Cancer-Related Health Outcomes: A 12-Month Follow-up of the Phys-Can RCT | Cancer | CANCER | Click here for additional data file.Supplemental material, sj-docx-1-ict-10.1177_15347354231178869 for The Role of Long-Term Physical Activity in Relation to Cancer-Related Health Outcomes: A 12-Month Follow-up of the Phys-Can RCT by Anne-Sophie Mazzoni, Ann Christin Helgesen Bjørke, Andreas Stenling, Sussanne Börjeson... | PMC10331773 |
References | PMC10331773 | |||
1. Introduction | precancerous lesions, CRC, adenomatous polyps, inflammation, cancer, adenomatous polyp, dysplasia, carcinoma, colon cancer, high-grade dysplasia, adenoma, deaths | PRECANCEROUS LESIONS, CARCINOGENESIS, ADENOMATOUS POLYPS, INFLAMMATION, DISEASE, ADENOMATOUS POLYP, DYSPLASIA, CARCINOMA, COLON CANCER, CANCER, INSULIN RESISTANCE, ADENOMA, COLORECTAL CANCER | These authors contributed equally to this work.Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of precancerous lesions is key to preventing carcinogenesis progression. Natural compounds like curcumin and anthocyan... | PMC10537228 |
2. Materials and Methods | PMC10537228 | |||
2.1. Study Design and Participants | flat serrated, polyp, adenomatous polyps, cancer, adenomatous polyp, blood coagulation, Status ≤, colorectal tract, adenomas | HYPERPLASTIC POLYPS, CANCER, ADENOMATOUS POLYP, ADENOMATOUS POLYPS | A randomized, double-blind, placebo-controlled, phase II presurgical trial in patients with adenomatous polyps of the colon was conducted (MiRACol trial). Participants received either anthocyanin plus curcumin or a placebo for 4–6 weeks before undergoing polypectomy. To be eligible for the trial, patients had to be bet... | PMC10537228 |
2.2. Study Procedures | adenomatous polyp, polyp | ADENOMATOUS POLYP | During screening, subjects underwent colonoscopy with evaluation for the presence of adenomatous polyp ≥1 cm and collection of tissue biopsies of the polyp and perilesional normal tissue. Once the histological confirmation and eligibility criteria were verified, eligible patients were randomly assigned to either the ac... | PMC10537228 |
2.3. Dietary Supplements | Indena SpA (Milan, Italy) generously contributed curcumin (MerivaMerivaMirtoselect | PMC10537228 | ||
2.4. Circulating Biomarkers Assessment | TNF-α | BLOOD | Fasting blood samples were obtained at baseline and the end of the study after 4–6 weeks of intervention. Blood samples were processed into serum and aliquots were frozen at −80 °C until biomarkers measurements.We measured hs-CRP, glycemia, and insulin using the Abbott Alinity analyzer (Abbott Diagnostics, Abbott Park,... | PMC10537228 |
2.5. Statistical Analysis | The sample size calculation was based on data from our previous randomized trial on the same study population [We presented median values and interquartile ranges (IQR) of serum biomarkers at baseline and the end of the study, in changes in time from baseline and % changes, by treatment arm. Biomarker values below the ... | PMC10537228 | ||
4. Discussion | obesity, colorectal cancer, TNF-α, colorectal adenomas, inflammation, dysplasia, adenomatous polyp, carcinoma, colon carcinogenesis, Inflammation, satiety, adenoma | OBESITY, COLORECTAL CANCER, ADENOMATOUS POLYPS, INFLAMMATION, ABNORMAL CELL PROLIFERATION, ADENOMATOUS POLYP, CARCINOMA, DYSPLASIA, DYSPLASTIC, INFLAMMATION, ADENOMA, CHRONIC INFLAMMATION | The findings from our study provide valuable insights into the complex relationships between biomarkers and treatment outcomes of curcumin and anthocyanin in patients with adenomatous polyps. Notably, no significant differences in biomarker levels or their changes were observed across the treatment arms, indicating tha... | PMC10537228 |
5. Conclusions | dysplasia, colorectal adenomas | DISEASE PROGRESSION, DYSPLASIA, DISEASE CHARACTERISTIC | In conclusion, the combined treatment of curcumin and anthocyanins in patients with colorectal adenomas did not directly modulate circulating biomarkers. While the expected changes in biomarker levels were not observed, our study yielded intriguing results, shedding light on the complex interplay between metabolic and ... | PMC10537228 |
Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC10537228 | ||
Author Contributions | Conceptualization, D.M., I.M.B., H.J. and A.D.; methodology, A.D., H.J. and S.G.; formal analysis, S.G. and O.D.; investigation, D.M., I.M.B., H.J., V.A., T.B.W., M.O., B.B. and A.D.; resources, H.J., M.O. and A.D.; data curation, D.M., I.M.B., H.J., V.A., O.D. and S.G.; writing—original draft preparation, D.M., I.M.B.... | PMC10537228 | ||
Institutional Review Board Statement | ICH | The study was carried out in accordance with the Declaration of Helsinki (1964) guidelines and its amendments and the general principles of ICH Harmonised Tripartite Guidelines for Good Clinical Practice (ICH Topic E6, CPMP/ICH/135/95). At the beginning of the study, written informed consent, reviewed by the ethics com... | PMC10537228 | |
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10537228 | ||
Data Availability Statement | Data may be made available for collaborative studies upon reasonable request to the corresponding author. | PMC10537228 | ||
Conflicts of Interest | The authors declare no conflict of interest. | PMC10537228 | ||
ABSTRACT | Shuwen Yu and Benjie Wang have served as speakers for Jiangsu Hansoh Pharmaceutical Group Co., Ltd. Qiong Wu, Chao Pan, Xiangqing Yu, and Yuhui Liu are the employees of Jiangsu Hansoh Pharmaceutical Group Co., Ltd, the sponsor of the study, at the time of this study. The remaining authors declare no conflict of interes... | PMC10720486 | ||
KEYWORDS | PMC10720486 | |||
MATERIALS AND METHODS | PMC10720486 | |||
Study design | SAD) stage | RECRUITMENT | This was a randomized, double-blind, placebo-controlled phase 1 study, aiming at assessing the safety, tolerability, and PK characteristics of ibrexafungerp in healthy Chinese subjects. Two stages, the single ascending dose (SAD) stage and the multiple ascending dose (MAD) stage, were launched sequentially.This study w... | PMC10720486 |
Safety and tolerability assessments | SAD | ADVERSE EVENTS | Safety and tolerability assessments included adverse events (AEs) and serious AEs (SAEs) assessments from the signing of ICF until finishing assessments in the last visit of follow-up. Time intervals between the last dose and last visit of follow-up in SAD and MAD stages were both 7 days. Severity of AEs was classified... | PMC10720486 |
Sample collection and bioanalytical assay | SAD | In all three cohorts of the SAD stage, blood samples for ibrexafungerp concentration were collected predose (0 hour), and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours postdose. In 450 mg cohort of MAD stage, blood samples were collected predose (0 hour), and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, and... | PMC10720486 | |
Pharmacokinetic data analysis | PK data analyses were performed using the data from all enrolled subjects who had at least one plasma concentration post-dosing. PK parameters for ibrexafungerp were calculated with standard non-compartmental analysis using Phoenix WinNonlin (Certara USA, Inc., version 8.1) and were summarized by study part and cohort ... | PMC10720486 | ||
Statistical analysis | All analyses were performed by using SAS software (version 9.4, SAS Institute Inc., NC, USA) or Phoenix WinNonlin (version 8.0, Certara USA Inc., USA). Demographics and baseline characteristics as well as safety data were summarized descriptively for subjects who had received at least one dose of study drug. Mean (stan... | PMC10720486 | ||
RESULTS | PMC10720486 | |||
Demographic profile | SAD stage, SAD | In total, 70 subjects were randomized into this study (42 in the SAD stage and 28 in the MAD stage). For both stages, all subjects are Chinese with balanced distributions of age, sex, ethnicity, and BMI between ibrexafungerp and placebo groups (Demographic and clinical characteristics of subjects in the single ascendin... | PMC10720486 | |
Safety and tolerability | syncope, abdominal pain, diarrhea, TEAEs, SAD | ADVERSE EVENT | All 70 subjects received at least one dose of study drug and were included in the safety analysis sets. TEAEs were reported in 8 (66.7%), 11 (91.7%), 12 (100.0%), 12 (100.0%), and 12 (100.0%) subjects in SAD and MAD stages. All TEAEs were mild to moderate in severity. There were no SAEs, severe AEs, or AEs leading to w... | PMC10720486 |
Pharmacokinetic properties | SAD stage, SAD) stage, SAD | Plasma concentrations of ibrexafungerp were available for analysis in 60 healthy Chinese subjects (36 in the SAD stage and 24 in the MAD stage), and these 60 subjects were included in the PK analysis.After a single oral dose in the fasting state, the mean plasma concentration of ibrexafungerp generally increased with i... | PMC10720486 | |
DISCUSSION | diarrhea, abdominal pain, gastrointestinal degeneration, TEAEs, vomiting, SAD | GASTROINTESTINAL DISORDERS | This was the first study to assess the safety, tolerability, and PK of ibrexafungerp in healthy Chinese subjects. In the SAD stage, CWith respect to the safety of ibrexafungerp in healthy Chinese subjects, most TEAEs were mild to moderate, and resolved without medical interventions. The most common TEAEs in SAD and MAD... | PMC10720486 |
Conclusion | Following a single dose up to 1,500 mg and multiple doses up to 750 mg, ibrexafungerp was safe, well-tolerated, and displayed a favorable PK profile in healthy Chinese subjects, which was similar to those in the previous studies conducted overseas. These results support further clinical development of ibrexafungerp in ... | PMC10720486 | ||
ACKNOWLEDGMENTS | We would like to thank all of the investigators, staffs, all of the subjects and their families for their support in completing this trial during the outbreak of the COVID-19 pandemic. We thank Jiayang Song for carefully analyzing and reviewing the data and also appreciate Wen Jia, Peng Xia, and Chaonan Jin for providi... | PMC10720486 |
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