Two trials studying brexpiprazole in combination with sertraline "constitute one of the largest clinical development programs ever conducted in posttraumatic stress disorder (PTSD)."
Based on data from several phase 3 and phase 2 clinical trials, Otsuka Pharmaceutical Co., Ltd. and H. Lundbeck A/S submitted a supplemental new drug application (sNDA) to the FDA for brexpiprazole in combination with sertraline in the treatment of posttraumatic stress disorder (PTSD) in adults.1
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The combination proved to be effective in a phase 3 randomized, double-blind, 2-arm, flexible dose trial (NCT04124614), meeting its primary endpoint by demonstrating improvements from baseline Clinician-Administered PTSD Scale (CAPS-5) scores at week 10 (P < .05).2,3 The study included 416 adult (aged 18–65 years) patients with DSM-5 diagnosis of PTSD for a minimum of 6 months who were randomized to receive brexpiprazole (2-3 mg/day) plus sertraline or sertraline plus placebo. Up to 150 mg of sertraline were administered simultaneously with the placebo or brexpiprazole.
About NCT04124614
Trial Name: Brexpiprazole as Combination Therapy With Sertraline in Treatment of Adults With PTSD
Clinicaltrials.gov Identifier: NCT04124614
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
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 subjects with Post-Traumatic Stress Disorder.
The second phase 3 study (NCT04174170) was a randomized, double-blind, 3-arm, fixed dose trial that sought to evaluate its efficacy, safety and tolerability.2,4 The trial included a group who received fixed-dose brexpiprazole 2 mg/day plus sertraline 150 mg/day, a group who received brexpiprazole 3 mg/day plus sertraline 150 mg/day, and those who received sertraline 150 mg/day plus placebo. A total of 553 participants with a DSM-5 diagnosis of PTSD were included in the trial. This phase 3 trial, however, failed to meet the primary endpoint of reduction in CAPS-5 scores (P > .05).
The results from both phase 3 studies were announced in September 2023. “The two trials constitute one of the largest clinical development programs ever conducted in PTSD. We will analyze the dataset to further determine the potential of brexpiprazole as combination therapy with sertraline in comprehensively addressing symptoms across the PTSD core domains,” Johan Luthman, DDS, PhD, executive vice president and head of Research & Development at Lundbeck, said in a press statement at the time.2
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The clinical phase 2 study was also a flexible dose trial and included 321 patients with PTSD. It demonstrated statistical superiority of combination brexpiprazole and sertraline over sertraline plus placebo.
The studies also indicated that the drug combination was generally well-tolerated, with reports that the safety profile was similar to that seen with brexpiprazole in studies of other psychiatric conditions (ie, agitation associated with Alzheimer, schizophrenia, and adjunctive treatment of major depressive disorder).1,2 Dyspepsia, fatigue, weight increase, akathisia, and somnolence were the most commonly reported adverse events associated with the combination treatment. Interestingly, discontinuation rates due to adverse events was higher in the sertraline and placebo treatment groups than in the combination groups and were and 7.6% and 3.7%, respectively.
Brexpiprazole is currently approved by the FDA for the treatment of schizophrenia in adults, adjunctive therapy to antidepressants for major depressive disorder in adults, and in May 2023 received approval for the treatment of agitation associated with dementia due to Alzheimer disease.
This article originally appeared in Psychiatric Times.
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