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

A Phase 3, Multicenter, Randomized, Double-blind Trial of Fixed-Dose Brexpiprazole as Combination Therapy With Sertraline in the Treatment of Adults With Post-traumatic Stress Disorder

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.

Study Overview

• Status: Completed
• Conditions: Post Traumatic Stress Disorder
• Intervention / Treatment: Other: Placebo; Drug: Brexpiprazole; Drug: Sertraline; Drug: Brexpiprazole

• Study Type: Interventional
• Enrollment (Actual): 591
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10010
      • For additional information regarding sites, contact 844-687-8522

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; All enrolled participants received brexpiprazole-matched placebo tablets and sertraline-matched placebo tablets during the 1-week placebo run-in period.	Other: Placebo; Pill
Experimental: Brexpiprazole (2 mg) + Sertraline; 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: Brexpiprazole; 3 mg pill; Other Names: Rexulti; Drug: Sertraline; 150 mg pill; Other Names: Zoloft; Drug: Brexpiprazole; 2 mg pill; Other Names: Rexulti
Experimental: Brexpiprazole (3 mg) + Sertraline; 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; 3 mg pill; Other Names: Rexulti; Drug: Sertraline; 150 mg pill; Other Names: Zoloft; Drug: Brexpiprazole; 2 mg pill; Other Names: Rexulti
Experimental: Sertraline + Placebo; 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.	Other: Placebo; Pill; Drug: Sertraline; 150 mg pill; Other Names: Zoloft

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Global Impression - Severity (CGI-S) Score	The CGI-S is a standardized, clinician-administered global rating scale that measures disease severity. To assess CGI-S, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices include: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. The score 0 (not assessed) was to be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7. A higher score on the CGI-S represents a higher severity of disease. LS mean was determined by 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
Change in Brief Inventory of Psychosocial Functions (B-IPF) Score	The B-IPF is a short patient-reported questionnaire consisting of 7 questions which measure PTSD-specific psychosocial function on a 7-point Likert scale (0 = not at all to 6 = very much, and a not applicable option) with a recall period of 30 days. The B-IPF measures the concepts of romantic relationships, parenting, family, friendships and socializing, work, education, and self-care. Total score ranges from 0-100 and is calculated by summing the completed scale items, dividing by the maximum possible score of all items and multiplying by 100. Higher scores indicate greater impairment. LS mean was determined by 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 12

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2019
• Primary Completion (Actual): July 25, 2023
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: November 21, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: PTSD
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Dopamine Agonists; Antidepressive Agents; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Brexpiprazole; Sertraline
• Other Study ID Numbers: 331-201-00072

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 an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; 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