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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Stress Disorders, Post-Traumatic

Intervention / Treatment
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* Drug: Brexpiprazole
* Drug: Sertraline
* Drug: Brexpiprazole Matching Placebo
* Drug: Sertraline Matching Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brexpiprazole + Sertraline<br>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<br>* Brexpiprazole oral tablets.<br>* Other names: OPC-331;Drug: Sertraline<br>* Sertraline oral capsules.<br>* Other names: Zoloft;Drug: Sertraline Matching Placebo<br>* Sertraline matching placebo oral capsules.<br>|
| Experimental: Brexpiprazole<br>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<br>* Brexpiprazole oral tablets.<br>* Other names: OPC-331;Drug: Sertraline Matching Placebo<br>* Sertraline matching placebo oral capsules.<br>|
| Active Comparator: Sertraline<br>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<br>* Sertraline oral capsules.<br>* Other names: Zoloft;Drug: Brexpiprazole Matching Placebo<br>* Brexpiprazole matching placebo oral tablets.<br>Drug: Sertraline Matching Placebo<br>* Sertraline matching placebo oral capsules.<br>|
| Placebo Comparator: Placebo<br>Participants received oral brexpiprazole matching placebo tablet and oral sertraline matching placebo capsules up to Week 12. | Drug: Brexpiprazole Matching Placebo<br>* Brexpiprazole matching placebo oral tablets.<br>Drug: Sertraline Matching Placebo<br>* Sertraline matching placebo oral capsules.<br>|

What is the study measuring?
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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 |