A Phase 1b, Randomized, Double-blind, Placebo-controlled Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Oral Doses of SEP-380135 in Adults With Schizophrenia or With a Major Depressive Episode Associated With Bipolar I or II Disorder or Major Depressive Disorder
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- All Cohorts: Change From Baseline in BMI
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple dose oral administration of SEP-380135 in participants with schizophrenia or with a major depressive episode associated with bipolar I or II disorder or major depressive disorder (MDD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI from 18.0 to 35.0 kilograms per square meter (kg/m^2) (inclusive).
- •Participants with a primary diagnosis of schizophrenia (cohorts 1 to 3) or bipolar I or II disorder or MDD (cohort 4) for at least 1 year (at screening), as established by clinical review, using the DSM-5 as a reference, and confirmed using the Mini international neuropsychiatric interview (MINI).
- •For cohorts 1 to 3: deemed to have residual symptoms of schizophrenia at screening (i.e., be at least "mildly ill" per CGI-S criteria [CGI-S greater than or equal to (≥) 3]) and a PANSS criteria of less than or equal to (≤)
- •For cohort 4 only: deemed to be currently experiencing an MDE. Participants must be at least "moderately ill" per CGI-S criteria (CGI-S ≥ 4).
- •Ability to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the PI, to comply with all the requirements of the trial.
排除标准
- •Attempted suicide within 12 months prior to screening
- •A disorder or history of a condition, or previous gastrointestinal conditions that may interfere with drug absorption, distribution, metabolism, excretion, gastrointestinal motility, or pH, or a history of clinically significant abnormality of the hepatic (including participants with moderate [Child-Pugh Class B] and severe [Child-Pugh Class C] hepatic impairment) or renal system (a glomerular filtration rate less than (<) 60 milliliters per minute (mL/min)), or a history of malabsorption, bowel resection, bariatric surgery or gastric band/lap band surgery, or is on medications that might interfere with gastric motility.
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin ≥ 2 times the upper limit of the reference ranges provided by the safety laboratory at screening, or total bilirubin ≥ 2 times the upper limit of reference (except for participants with Gilbert's syndrome or similar condition).
- •Has any clinically significant unstable medical condition, clinically significant chronic disease, or any psychiatric symptom or diagnosis that in the opinion of the investigator, MM, or sponsor would pose a risk to the participant or the scientific objectives of the trial.
- •Note: Other protocol-specified Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1
Participants receive SEP-380135 Dose Level 1, orally once daily (QD) from Day 1 to Day 14.
干预措施: SEP-380135 (Drug)
Cohort 2
Participants receive SEP-380135 Dose Level 2 orally once daily (QD) from Day 1 through Day 14.
干预措施: SEP-380135 (Drug)
Cohort 3
Participants receive SEP-380135 Dose Level 3 orally once daily (QD) from Day 1 through Day 14.
干预措施: SEP-380135 (Drug)
Cohort 4
Participants receive SEP-380135 Dose Level 4 orally once daily (QD) from Day 1 through Day 14.
干预措施: SEP-380135 (Drug)
Placebo
Participants receive SEP-380135 matching-placebo orally orally once daily (QD) from Day 1 to Day 14.
干预措施: Placebo (Drug)
结局指标
主要结局
All Cohorts: Change From Baseline in BMI
时间窗: Baseline, Day 18
All Cohorts: Change From Baseline in Weight
时间窗: Baseline, Day 18
All Cohorts: Actual Values of Body Mass Index (BMI)
时间窗: Up to Day 18
All Cohorts: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Treatment Emergent Adverse Events (TEAEs) Leading to Trial Discontinuation
时间窗: Up to Day 44
All Cohorts: Percentage of Participants With Suicidal Ideation or Suicidal Behavior Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to Day 18
All Cohorts: Percentage of Participants With Withdrawal Symptoms Using the 20-Item Physician Withdrawal Checklist (PWC-20)
时间窗: Up to Day 44
All Cohorts: Percentage of Participants With Change From Baseline in Potentially Clinically Relevant Laboratory Tests
时间窗: Baseline, Day 18
All Cohorts: Percentage of Participants With Change From Baseline in Potentially Clinically Relevant Vital Signs
时间窗: Baseline, Day 18
All Cohorts: Percentage of Participants With Change From Baseline in Potentially Clinically Relevant Orthostatic Effects
时间窗: Baseline, Day 18
All Cohorts: Actual Values of Weight
时间窗: Up to Day 18
All Cohorts: Actual Values of Waist Circumference
时间窗: Up to Day 18
All Cohorts: Change From Baseline in Waist Circumference
时间窗: Baseline, Day 18
All Cohorts: Percentage of Participants With Change From Baseline in 12-Lead Electrocardiogram (ECG)
时间窗: Baseline, Day 18
All Cohorts: Actual Values of QT interval corrected using Fridericia's Formula (QTcF)
时间窗: Up to Day 18
All Cohorts: Change From Baseline in QTcF
时间窗: Baseline, Day 18
Cohorts 1, 2, and 3: Actual Values of Clinician-Administered Dissociative States Scale (CADSS) Score
时间窗: Up to Day 18
Cohorts 1, 2, and 3: Change From Baseline in CADSS Score
时间窗: Baseline, Day 18
All Cohorts: Actual Values of Drug Effect Questionnaire (DEQ) Scored Using Visual Analog Scale Score
时间窗: Up to Day 18
All Cohorts: Change From Baseline in DEQ Scored Using Visual Analog Scale Score
时间窗: Baseline, Day 18
Cohorts 1, 2, and 3: Actual Values of Barnes Akathisia Rating Scale (BARS) Score
时间窗: Up to Day 18
Cohorts 1, 2, and 3: Change From Baseline in BARS Score
时间窗: Baseline, Day 18
Cohorts 1, 2, and 3: Actual Values of Abnormal Involuntary Movement Scale (AIMS) Score
时间窗: Up to Day 18
Cohorts 1, 2, and 3: Change From Baseline in AIMS Score
时间窗: Baseline, Day 18
Cohorts 1, 2, and 3: Actual Values of Simpson Angus Scale (SAS) Score
时间窗: Up to Day 18
Cohorts 1, 2, and 3: Change From Baseline in SAS Score
时间窗: Baseline, Day 18
Cohorts 1, 2, and 3: Actual Values of Positive and Negative Syndrome Scale (PANSS) Score
时间窗: Up to Day 18
Cohorts 1, 2, and 3: Change From Baseline in PANSS Score
时间窗: Baseline, Day 18
All Cohorts: Actual Values of Clinical Global Impressions-Severity Scale (CGI-S) Score
时间窗: Up to Day 18
All Cohorts: Change From Baseline in CGI-S Score
时间窗: Baseline, Day 18
Cohorts 1, 2, and 3: Actual Values of Calgary Depression Scale for Schizophrenia (CDSS) Score
时间窗: Up to Day 18
Cohorts 1, 2, and 3: Change From Baseline in CDSS Score
时间窗: Baseline, Day 18
All Cohorts: Percentage of Participants With Change From Baseline in Physical Examinations
时间窗: Baseline, Day 18
All Cohorts: Percentage of Participants With Change From Baseline in Neurological Examinations
时间窗: Baseline, Day 18
Cohort 4: Actual Values of Hamilton Anxiety Rating Scale (HAM-A) Score
时间窗: Up to Day 18
Cohort 4: Change From Baseline in HAM-A Score
时间窗: Baseline, Day 18
Cohort 4: Actual Values of Montgomery-Asberg Depression Rating Scale (MADRS) Score
时间窗: Up to Day 18
Cohort 4: Change From Baseline in MADRS Score
时间窗: Baseline, Day 18
Cohort 4: Actual Values of Young Mania Rating Scale (YMRS) Score
时间窗: Up to Day 18
Cohort 4: Change From Baseline in YMRS Score
时间窗: Baseline, Day 18
All Cohorts: Percentage of Participants With Changes in Quantitative Sleep Parameters Measured Using Electroencephalography (EEG)
时间窗: Up to Day 17
All Cohorts: Apparent Clearance (CL/F) of SEP-380135
时间窗: Day 14
All Cohorts: Volume of Distribution (Vz/F) of SEP-380135
时间窗: Day 14
All Cohorts: Maximum Plasma Concentration (Cmax) of SEP-380135
时间窗: Day 14
All Cohorts: Area Under the Drug Concentration-time Curve From Time Zero Predose to 24 hours Postdose (AUC0-24h) of SEP-380135
时间窗: Day 14
次要结局
- All Cohorts: Cmax of SEP-380135 and its Metabolites(Days 1 and 14)
- All Cohorts: Time to Maximum Plasma Concentration (tmax) of SEP-380135 and its Metabolites(Days 1 and 14)
- All Cohorts: AUC0-24h of SEP-380135 and its Metabolites(Days 1 and 14)
- All Cohorts: Observed Plasma Concentration at 24 hours Postdose (C24h) of SEP-380135(Days 1 and 14)
- All Cohorts: Terminal Phase Elimination Half-Life (t1/2,z) of SEP-380135 and its Metabolites(Day 14)
- All Cohorts: Serum Concentration of SEP-380135 at Steady-State(Day 14)