Brexpiprazole as Combination Therapy With Sertraline in the Treatment of Adults With Post-traumatic Stress Disorder

NCT04174170 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 331-201-00072
• Study Type: interventional
• Target: 591
• 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 fixed-dose brexpiprazole + sertraline combination treatment in adult subjects 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 was a structured interview designed to assess PTSD diagnostic status and 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 categories: Category B: Intrusion symptoms (5 items); Category C: Avoidance symptoms (2 items); Category D: Cognition and mood symptoms (7 items); Category E: Arousal and 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, to yield 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 effect of treatment, trial site, visit week, and an interaction term of treatment by visit week, and included the interaction term of baseline values by visit week 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 of Psychosocial Functions (B-IPF) Score

  Baseline, Week 12

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Brexpiprazole (2 mg) + Sertraline

EXPERIMENTAL

Randomized participants received brexpiprazole 2 milligrams (mg), orally, once daily (QD) in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the double-blind treatment (DBT) period.

Drug: Sertraline; Drug: Brexpiprazole

Brexpiprazole (3 mg) + Sertraline

EXPERIMENTAL

Randomized participants received brexpiprazole 3 mg, orally, QD in combination with sertraline, 150 mg, orally, QD from Week 1 to Week 12 of the DBT period.

Drug: Brexpiprazole; Drug: Sertraline

Sertraline + Placebo

EXPERIMENTAL

Randomized participants received sertraline 150 mg, orally, QD, in combination 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 (3 mg) + Sertraline

Sertraline DRUG

150 mg pill

Also known as: Zoloft

Brexpiprazole (2 mg) + Sertraline; Brexpiprazole (3 mg) + 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 post-traumatic stress disorder (PTSD), diagnosed according to 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 development 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

New York, New York, 10010, United States

Location

Related Publications (1)

• Davis LL, Behl S, Lee D, Zeng H, Skubiak T, Weaver S, Hefting N, Larsen KG, Hobart M. Fixed-Dose Brexpiprazole and Sertraline Combination Therapy for the Treatment of Posttraumatic Stress Disorder: A Phase 3, Randomized Trial. J Clin Psychopharmacol. 2025 Nov-Dec 01;45(6):580-589. doi: 10.1097/JCP.0000000000002076. Epub 2025 Sep 22.

  PMID: 40982703 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: November 21, 2019
• First Posted: November 22, 2019
• Study Start: October 30, 2019
• Primary Completion: July 25, 2023
• Study Completion: August 15, 2023
• Last Updated: May 30, 2025
• Results First Posted: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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)