A Study of SEP-380135 in Adults With Schizophrenia or Major Depressive Episode

NCT07549581 | Completed Phase 1 FDA Drug

• 1 other identifier: 384-201-00002
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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).

Conditions

Schizophrenia; Major Depressive Disorder (MDD); Bipolar Disorder

Outcome Measures

Primary Outcomes (44)

• 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 Outcomes (6)

• 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

Study Arms (5)

Cohort 1

EXPERIMENTAL

Participants receive SEP-380135 Dose Level 1, orally once daily (QD) from Day 1 to Day 14.

Drug: SEP-380135

Cohort 2

EXPERIMENTAL

Participants receive SEP-380135 Dose Level 2 orally once daily (QD) from Day 1 through Day 14.

Drug: SEP-380135

Cohort 3

EXPERIMENTAL

Participants receive SEP-380135 Dose Level 3 orally once daily (QD) from Day 1 through Day 14.

Drug: SEP-380135

Cohort 4

EXPERIMENTAL

Participants receive SEP-380135 Dose Level 4 orally once daily (QD) from Day 1 through Day 14.

Drug: SEP-380135

Placebo

PLACEBO COMPARATOR

Participants receive SEP-380135 matching-placebo orally orally once daily (QD) from Day 1 to Day 14.

Drug: Placebo

Interventions

SEP-380135 DRUG

oral capsule.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Placebo DRUG

Placebo capsule.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (1)

Collaborative Neuroscience Research, LLC

Los Alamitos, California, 90720, United States

Location

Related Links

• Otsuka Clinical Trials website

MeSH Terms

Conditions

Schizophrenia; Depressive Disorder, Major; Bipolar Disorder

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Bipolar and Related Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2026
• First Posted: April 24, 2026
• Study Start: November 7, 2024
• Primary Completion: September 12, 2025
• Study Completion: September 12, 2025
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform: https://vivli.org/ourmember/Otsuka/

Locations

US (1)