Efficacy and Safety of a Combination of Olanzapine and Samidorphan in Adult Patients With an Acute Exacerbation of Schizophrenia
Steven G. Potkin, Jelena Kunovac, Bernard L. Silverman, Adam Simmons, Ying Jiang, Lauren DiPetrillo, David McDonnell
Abstract
OBJECTIVE: To assess the antipsychotic efficacy and safety of a combination of olanzapine and samidorphan (OLZ/SAM). METHODS: This 4-week, phase 3, randomized, double-blind, placebo- and olanzapine-controlled study was conducted from December 2015 to June 2017 in adults with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria who were experiencing an acute exacerbation. Patients were randomized 1:1:1 to OLZ/SAM, olanzapine monotherapy, or placebo. The primary and key secondary efficacy endpoint assessed was the change in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness Scale (CGI-S) score between baseline and week 4, respectively, for OLZ/SAM versus placebo. Safety monitoring occurred throughout. RESULTS: 401 patients received ≥ 1 dose of study drug; 352 completed treatment. Treatment with OLZ/SAM resulted in significant improvements versus placebo in PANSS total and CGI-S scores from baseline to week 4 (least squares [LS] mean ± SE: -6.4 ± 1.8 [P < .001] and -0.38 ± 0.12 [P = .002], respectively). Olanzapine treatment resulted in similar improvements (PANSS and CGI-S LS mean ± SE of -5.3 ± 1.84 [P = .004] and -0.44 ± 0.12 [P < .001], respectively). Adverse events (AEs) occurred in 54.5%, 54.9%, and 44.8% of patients on OLZ/SAM, olanzapine, and placebo, respectively. Weight gain, somnolence, dry mouth, anxiety, and headache were the most common AEs (ie, ≥ 5%) with active treatment. CONCLUSIONS: OLZ/SAM treatment resulted in statistically and clinically significant efficacy improvements over 4 weeks versus placebo in adults with acutely exacerbated schizophrenia. Improvements were similar to those observed with olanzapine. OLZ/SAM was well tolerated, with a safety profile similar to that of olanzapine. TRIAL REGISTRATIONS: ClinicalTrials.gov identifier: NCT02634346; EudraCT number: 2015-003373-15.