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

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

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).

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Bipolar Disorder; Major Depressive Disorder (MDD)
• Intervention / Treatment: Drug: SEP-380135; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Alamitos, California, United States, 90720
      • Collaborative Neuroscience Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants receive SEP-380135 Dose Level 1, orally once daily (QD) from Day 1 to Day 14.	Drug: SEP-380135; oral capsule.
Experimental: Cohort 2; Participants receive SEP-380135 Dose Level 2 orally once daily (QD) from Day 1 through Day 14.	Drug: SEP-380135; oral capsule.
Experimental: Cohort 3; Participants receive SEP-380135 Dose Level 3 orally once daily (QD) from Day 1 through Day 14.	Drug: SEP-380135; oral capsule.
Experimental: Cohort 4; Participants receive SEP-380135 Dose Level 4 orally once daily (QD) from Day 1 through Day 14.	Drug: SEP-380135; oral capsule.
Placebo Comparator: Placebo; Participants receive SEP-380135 matching-placebo orally orally once daily (QD) from Day 1 to Day 14.	Drug: Placebo; Placebo capsule.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

Helpful Links

• Otsuka Clinical Trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2024
• Primary Completion (Actual): September 12, 2025
• Study Completion (Actual): September 12, 2025

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Mood Disorders; Depressive Disorder; Schizophrenia; Bipolar Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 384-201-00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing 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.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No