Bipolar Disorder, Major Depressive Disorder (MDD), Schizophrenia
Conditions
Brief summary
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).
Interventions
DRUGSEP-380135
oral capsule.
DRUGPlacebo
Placebo capsule.
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 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 (≤) 75. 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.
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| All Cohorts: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Treatment Emergent Adverse Events (TEAEs) Leading to Trial Discontinuation | Up to Day 44 |
| All Cohorts: Percentage of Participants With Suicidal Ideation or Suicidal Behavior Using the Columbia-Suicide Severity Rating Scale (C-SSRS) | Up to Day 18 |
| All Cohorts: Percentage of Participants With Withdrawal Symptoms Using the 20-Item Physician Withdrawal Checklist (PWC-20) | Up to Day 44 |
| All Cohorts: Percentage of Participants With Change From Baseline in Potentially Clinically Relevant Laboratory Tests | Baseline, Day 18 |
| All Cohorts: Percentage of Participants With Change From Baseline in Potentially Clinically Relevant Vital Signs | Baseline, Day 18 |
| All Cohorts: Percentage of Participants With Change From Baseline in Potentially Clinically Relevant Orthostatic Effects | Baseline, Day 18 |
| All Cohorts: Actual Values of Weight | Up to Day 18 |
| All Cohorts: Change From Baseline in Weight | Baseline, Day 18 |
| All Cohorts: Actual Values of Body Mass Index (BMI) | Up to Day 18 |
| All Cohorts: Change From Baseline in BMI | Baseline, Day 18 |
| All Cohorts: Actual Values of Waist Circumference | Up to Day 18 |
| All Cohorts: Change From Baseline in Waist Circumference | Baseline, Day 18 |
| All Cohorts: Percentage of Participants With Change From Baseline in 12-Lead Electrocardiogram (ECG) | Baseline, Day 18 |
| All Cohorts: Actual Values of QT interval corrected using Fridericia's Formula (QTcF) | Up to Day 18 |
| All Cohorts: Change From Baseline in QTcF | Baseline, Day 18 |
| Cohorts 1, 2, and 3: Actual Values of Clinician-Administered Dissociative States Scale (CADSS) Score | Up to Day 18 |
| Cohorts 1, 2, and 3: Change From Baseline in CADSS Score | Baseline, Day 18 |
| All Cohorts: Actual Values of Drug Effect Questionnaire (DEQ) Scored Using Visual Analog Scale Score | Up to Day 18 |
| All Cohorts: Change From Baseline in DEQ Scored Using Visual Analog Scale Score | Baseline, Day 18 |
| Cohorts 1, 2, and 3: Actual Values of Barnes Akathisia Rating Scale (BARS) Score | Up to Day 18 |
| Cohorts 1, 2, and 3: Change From Baseline in BARS Score | Baseline, Day 18 |
| Cohorts 1, 2, and 3: Actual Values of Abnormal Involuntary Movement Scale (AIMS) Score | Up to Day 18 |
| Cohorts 1, 2, and 3: Change From Baseline in AIMS Score | Baseline, Day 18 |
| Cohorts 1, 2, and 3: Actual Values of Simpson Angus Scale (SAS) Score | Up to Day 18 |
| Cohorts 1, 2, and 3: Change From Baseline in SAS Score | Baseline, Day 18 |
| Cohorts 1, 2, and 3: Actual Values of Positive and Negative Syndrome Scale (PANSS) Score | Up to Day 18 |
| Cohorts 1, 2, and 3: Change From Baseline in PANSS Score | Baseline, Day 18 |
| All Cohorts: Actual Values of Clinical Global Impressions-Severity Scale (CGI-S) Score | Up to Day 18 |
| All Cohorts: Change From Baseline in CGI-S Score | Baseline, Day 18 |
| Cohorts 1, 2, and 3: Actual Values of Calgary Depression Scale for Schizophrenia (CDSS) Score | Up to Day 18 |
| Cohorts 1, 2, and 3: Change From Baseline in CDSS Score | Baseline, Day 18 |
| All Cohorts: Percentage of Participants With Change From Baseline in Physical Examinations | Baseline, Day 18 |
| All Cohorts: Percentage of Participants With Change From Baseline in Neurological Examinations | Baseline, Day 18 |
| Cohort 4: Actual Values of Hamilton Anxiety Rating Scale (HAM-A) Score | Up to Day 18 |
| Cohort 4: Change From Baseline in HAM-A Score | Baseline, Day 18 |
| Cohort 4: Actual Values of Montgomery-Asberg Depression Rating Scale (MADRS) Score | Up to Day 18 |
| Cohort 4: Change From Baseline in MADRS Score | Baseline, Day 18 |
| Cohort 4: Actual Values of Young Mania Rating Scale (YMRS) Score | Up to Day 18 |
| Cohort 4: Change From Baseline in YMRS Score | Baseline, Day 18 |
| All Cohorts: Percentage of Participants With Changes in Quantitative Sleep Parameters Measured Using Electroencephalography (EEG) | Up to Day 17 |
| All Cohorts: Apparent Clearance (CL/F) of SEP-380135 | Day 14 |
| All Cohorts: Volume of Distribution (Vz/F) of SEP-380135 | Day 14 |
| All Cohorts: Maximum Plasma Concentration (Cmax) of SEP-380135 | Day 14 |
| All Cohorts: Area Under the Drug Concentration-time Curve From Time Zero Predose to 24 hours Postdose (AUC0-24h) of SEP-380135 | Day 14 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Outcome results
None listed