Brexpiprazole as Combination Therapy With Sertraline in Treatment of Adults With PTSD

NCT04124614 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 331-201-00071
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a 12-week, multicenter, randomized, double-blind trial evaluating the efficacy, safety, and tolerability of brexpiprazole + sertraline combination treatment in adult participants with Post-Traumatic Stress Disorder.

Conditions

Post Traumatic Stress Disorder

Keywords

PTSD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total Score

  CAPS-5 is a structured interview designed to assess PTSD diagnostic status \& symptoms severity as defined by DSM-5. CAPS-5 total score was calculated by summing severity scores for 20 DSM-5 PTSD symptoms (items 1-20) from following categories: Category B: Intrusion symptoms (5 items); Category C: Avoidance symptoms (2 items); Category D: Cognition \& mood symptoms (7 items); Category E: Arousal \& reactivity symptoms (6 items). CAPS-5 total score was imputed by adding all subscores from categories B, C, D, E. Each symptom was scored 0= Absent to 4= Extreme/incapacitating, yielding a score range of 0-80. Higher scores indicate worse outcome. Least squares (LS) mean was determined by Mixed-effect model repeated measures (MMRM) method with fixed class effect terms for treatment, trial site, visit, previous treatment intervention for PTSD (Yes/No), \& an interaction term of treatment by visit, \& include the interaction term of baseline values of CAPS-5 total score by visit as a covariate.

  Baseline (Week 1), Week 10

Secondary Outcomes (2)

• Change in Clinical Global Impression - Severity (CGI-S) Score

  Baseline (Week 1), Week 10

• Change in Brief Inventory or Psychosocial Functions (B-IPF) Score

  Baseline (Day 1), Week 12

Study Arms (3)

Placebo

OTHER

All enrolled participants received brexpiprazole-matched placebo tablets and sertraline-matched placebo tablets during the 1-week placebo run-in period.

Other: Placebo

Brexpiprazole + Sertraline

EXPERIMENTAL

Randomized participants received brexpiprazole as a flexible dose 2 milligrams (mg) to 3 mg, orally, once daily (QD) along with sertraline, at a fixed dose of 150 mg, orally, QD from Week 1 to Week 12 of the double-blind treatment (DBT) period.

Drug: Brexpiprazole; Drug: Sertraline

Sertraline + Placebo

EXPERIMENTAL

Randomized participants received sertraline, 150 mg, orally, QD along with sertraline matching placebo, orally, QD from Week 1 to Week 12 of the DBT period.

Drug: Sertraline; Other: Placebo

Interventions

Brexpiprazole DRUG

3 mg pill

Also known as: Rexulti

Brexpiprazole + Sertraline

Sertraline DRUG

150 mg pill

Also known as: Zoloft

Brexpiprazole + Sertraline; Sertraline + Placebo

Placebo OTHER

Pill

Placebo; Sertraline + Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent.
• Participants who have PTSD, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), and confirmed by the Mini International Neuropsychiatric Interview (MINI).
• Onset of symptoms meeting the DSM-5 criteria for PTSD symptoms for a minimum of 6 months prior to screening.

You may not qualify if:

• The index traumatic event that led to the develop of PTSD took place \> 9 years before screening.
• The index traumatic event occurred before age 16.
• Participants who have experienced a traumatic event within 3 months of screening.
• Participants who are receiving disability payments because of PTSD or any other psychiatric disorder; unless the disability payments will not be impacted by potential improvements demonstrated in the trial.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (1)

For additional information regarding sites, contact 844-687-8522

San Diego, California, 92103, United States

Location

Related Publications (1)

• Davis LL, Behl S, Lee D, Zeng H, Skubiak T, Weaver S, Hefting N, Larsen KG, Hobart M. Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder: A Phase 3 Randomized Clinical Trial. JAMA Psychiatry. 2025 Mar 1;82(3):218-227. doi: 10.1001/jamapsychiatry.2024.3996.

  PMID: 39693081 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

brexpiprazole; Sertraline

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Global Clinical Development
• Organization: Otsuka Pharmaceutical Development & Commercialization, Inc

clinicaltransparency@otsuka-us.com

1-609-524-6788

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2019
• First Posted: October 11, 2019
• Study Start: October 17, 2019
• Primary Completion: July 19, 2023
• Study Completion: August 8, 2023
• Last Updated: June 13, 2025
• Results First Posted: June 13, 2025

Record last verified: 2025-05

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 an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com

Locations

US (1)