A Study of Flexible Dose Brexpiprazole as Monotherapy or Combination Therapy in the Treatment of Adults With Post-traumatic Stress Disorder (PTSD)

A Phase 2, Multicenter, Randomized, Double-blind, Placebo- and Active-controlled Trial of Brexpiprazole (1 - 3 mg/Day) as Monotherapy or as Combination Therapy in the Treatment of Adults With Post-traumatic Stress Disorder

To evaluate the safety, efficacy and tolerability of brexpiprazole (with placebo) as monotherapy or combination therapy with Zoloft (sertraline) in adults with PTSD.

Study Overview

• Status: Completed
• Conditions: Stress Disorders, Post-Traumatic
• Intervention / Treatment: Drug: Brexpiprazole; Drug: Sertraline; Drug: Sertraline Matching Placebo; Drug: Brexpiprazole Matching Placebo

Detailed Description

This trial is designed to assess the efficacy, safety and tolerability of flexible dose brexpiprazole as monotherapy or as combination therapy with Zoloft (Sertraline) in adult participants with PTSD.

This study will consist of a continuous 12-week, double-blind treatment period with a 14-day follow-up.

• Study Type: Interventional
• Enrollment (Actual): 336
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35404
      • Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Investigational Site
    • Rogers, Arkansas, United States, 72758
      • Investigational Site
  • California
    • Bellflower, California, United States, 90706
      • Investigational Site
    • Beverly Hills, California, United States, 90210
      • Investigational Site
    • Glendale, California, United States, 91206
      • Investigational Site
    • National City, California, United States, 91950
      • Investigational Site
    • Oceanside, California, United States, 92056
      • Investigational Site
    • Oceanside, California, United States, 92054
      • Investigational Site
    • Orange, California, United States, 92868
      • Investigational Site
    • Redlands, California, United States, 92374
      • Investigational Site
    • Riverside, California, United States, 92506
      • Investigational Site
    • San Diego, California, United States, 92103
      • Investigational Site
    • San Marcos, California, United States, 92078
      • Investigational Site
    • Torrance, California, United States, 90502
      • Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Investigational Site
  • Florida
    • Bradenton, Florida, United States, 34201
      • Investigational Site
    • Fort Lauderdale, Florida, United States, 33319
      • Investigational Site
    • Fort Myers, Florida, United States, 33912
      • Investigational Site
    • Gainesville, Florida, United States, 32607
      • Investigational Site
    • Jacksonville, Florida, United States, 32256
      • Investigational Site
    • North Miami, Florida, United States, 33161
      • Investigational Site
    • Orlando, Florida, United States, 32806
      • Investigational Site
    • Orlando, Florida, United States, 32801
      • Investigational Site
    • Tampa, Florida, United States, 33614
      • Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • Investigational Site
    • Decatur, Georgia, United States, 30030
      • Investigational Site
    • Roswell, Georgia, United States, 30076
      • Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Investigational Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Investigational Site
    • Princeton, New Jersey, United States, 08540
      • Investigational Site
  • New York
    • Brooklyn, New York, United States, 11235
      • Investigational Site
    • Cedarhurst, New York, United States, 11516
      • Investigational Site
    • New York, New York, United States, 10128
      • Investigational Site
    • Rochester, New York, United States, 14618
      • Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Investigational Site
    • Raleigh, North Carolina, United States, 27609
      • Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45215
      • Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Investigational Site
    • Oklahoma City, Oklahoma, United States, 73118
      • Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97214
      • Investigational Site
    • Salem, Oregon, United States, 97301
      • Investigational Site
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Investigational Site
    • Norristown, Pennsylvania, United States, 19403
      • Investigational Site
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Investigational Site
  • Texas
    • Bellaire, Texas, United States, 77401
      • Investigational Site
    • San Antonio, Texas, United States, 78229
      • Investigational Site
    • Wichita Falls, Texas, United States, 76309
      • Investigational Site
  • Washington
    • Everett, Washington, United States, 98201
      • Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male and female participants between the years of 18-65 with a diagnosis of PTSD (diagnosis can be made at screening)

Exclusion Criteria:

• Index trauma event >15 years before screening
• Index trauma event at age <16
• Any traumatic event within 3 months of screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brexpiprazole + Sertraline; Participants were administered oral brexpiprazole initial dose of 0.5 milligram (mg)/day plus sertraline initial dose of 50 mg/day. The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo based on dose titration/adjustment up to Week 12.	Drug: Brexpiprazole; Brexpiprazole oral tablets.; Other Names: OPC-34712; OPC-331; Drug: Sertraline; Sertraline oral capsules.; Other Names: Zoloft; Drug: Sertraline Matching Placebo; Sertraline matching placebo oral capsules.
Experimental: Brexpiprazole; Participants were administered oral brexpiprazole initial dose of 0.5 mg/day The dose was up titrated to brexpiprazole maximum dose of 3 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received sertraline matching placebo up to Week 12.	Drug: Brexpiprazole; Brexpiprazole oral tablets.; Other Names: OPC-34712; OPC-331; Drug: Sertraline Matching Placebo; Sertraline matching placebo oral capsules.
Active Comparator: Sertraline; Participants were administered oral sertraline initial dose of 50 mg/day. The dose was up titrated to sertraline maximum dose of 200 mg/day and continued thereafter up to Week 12 based on efficacy and tolerability. No dose reductions were allowed after Week 6 and no dose increments were allowed after Week 4. Participants also received brexpiprazole matching placebo and sertraline matching placebo based on dose titration/adjustment up to Week 12.	Drug: Sertraline; Sertraline oral capsules.; Other Names: Zoloft; Drug: Sertraline Matching Placebo; Sertraline matching placebo oral capsules.; Drug: Brexpiprazole Matching Placebo; Brexpiprazole matching placebo oral tablets.
Placebo Comparator: Placebo; Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12.	Drug: Sertraline Matching Placebo; Sertraline matching placebo oral capsules.; Drug: Brexpiprazole Matching Placebo; Brexpiprazole matching placebo oral tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinician-Administered Post-traumatic Stress Disorder (PTSD) Scale for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (CAPS-5) Total Score	CAPS-5:clinician-rated, structured interview to assess PTSD diagnostic status, symptoms severity as defined by DSM-5. CAPS-5 Past Week version of scale was completed at Baseline and at all visits after Baseline. CAPS-5 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 with range 0-80. Higher scores=worse outcome. Mixed model repeated measure (MMRM) was used for analysis.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2017
• Primary Completion (Actual): November 12, 2018
• Study Completion (Actual): November 12, 2018

Study Registration Dates

• First Submitted: January 24, 2017
• First Submitted That Met QC Criteria: January 24, 2017
• First Posted (Estimate): January 26, 2017

Study Record Updates

• Last Update Posted (Actual): December 8, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Sertraline; Brexpiprazole
• Other Study ID Numbers: 331-201-00061

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 which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (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