F232. A PHASE 3 STUDY TO DETERMINE THE ANTIPSYCHOTIC EFFICACY AND SAFETY OF ALKS 3831 IN ADULT PATIENTS WITH ACUTE EXACERBATION OF SCHIZOPHRENIA

Abstract

BackgroundALKS 3831, currently under development for the treatment of schizophrenia, is composed of a flexible dose of olanzapine (OLZ) and a fixed dose of 10 mg of samidorphan. In a Phase 2 study, ALKS 3831 mitigated OLZ-associated weight gain and exhibited antipsychotic efficacy similar to OLZ alone. This Phase 3 study assessed antipsychotic efficacy and safety of ALKS 3831 in patients with acute exacerbation of schizophrenia.MethodsThis was an international (USA, Ukraine, Serbia, and Bulgaria), 4-week, randomised, double-blind, active and placebo (PBO)-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (ClinicalTrials.gov: NCT02634346). Eligible patients (N=403) were randomised 1:1:1 to receive either ALKS 3831, OLZ, or PBO. Patients were treated in an inpatient setting for the first 2 weeks of the study and could be treated as inpatients or outpatients for the remaining 2 weeks. Patients were excluded if they received OLZ within 6 months prior to screening. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression–Severity (CGI-S), and CGI–Improvement (CGI-I) scales. Safety and tolerability were assessed as adverse events (AEs).ResultsOf 401 patients randomised and dosed to ALKS 3831, OLZ, and PBO, 91%, 89%, and 83% of patients, respectively, completed treatment. The most common reason for discontinuation was withdrawal by patient (6% in both the ALKS 3831 and PBO groups, and 7% in the OLZ group). Baseline characteristics were generally similar between groups; however, baseline mean body-mass index was higher in the OLZ group than in the ALKS 3831 group. Baseline mean ± standard deviation scores were 101.7 ± 11.9 for PANSS total score and 5.1 ± 0.7 for CGI-S score. The mean OLZ dose was 18.4 mg/day in both active treatment arms. Least squares (LS) mean difference ± standard error (SE) versus PBO from baseline to Week 4 in PANSS total score was –6.4 ± 1.8 (P<.001) for the ALKS 3831 group and –5.3 ± 1.8 (P=.004) for the OLZ group. LS mean difference ± SE vs PBO from baseline to Week 4 in CGI-S score was −0.38 ± 0.12 (P=.002) for the ALKS 3831 group and −0.44 ± 0.12 (P<.001) for the OLZ group. The percentage of patients with an improvement in PANSS response (≥30% improvement from baseline) at Week 4 was 60%, 54%, and 38% in the ALKS 3831, OLZ, and PBO groups, respectively. The percentage of patients with an improvement in CGI-I response (score of ≤2) at Week 4 was 58%, 51%, and 33% in the ALKS 3831, OLZ, and PBO groups, respectively. Discontinuation due to AEs was low in all groups. Common AEs (≥5%) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.DiscussionALKS 3831 demonstrated greater antipsychotic efficacy than PBO, as measured by the PANSS and CGI-S scale, and was similar to the active control, OLZ. The safety profile of ALKS 3831 was similar to OLZ.