A Phase 3 Study to Determine the Antipsychotic Efficacy and Safety of ALKS 3831 in Adult Patients With Acute Exacerbation of Schizophrenia

Background: ALKS 3831, under development for the treatment of schizophrenia, is composed of olanzapine and samidorphan. In a prior study, samidorphan mitigated olanzapine-associated weight gain and ALKS 3831 exhibited antipsychotic efficacy similar to olanzapine.

Methods: This was a phase 3, 4-week, randomized, double-blind, active and placebo-controlled study of ALKS 3831 in patients with acute exacerbation of schizophrenia (NCT02634346). Eligible patients (N=403) were randomized 1:1:1 to ALKS 3831, olanzapine, or placebo. Antipsychotic efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression–Severity (CGI-S) scale. Safety was assessed as adverse events (AEs).

Results: Of 401 patients who received ALKS 3831, olanzapine, or placebo, 91%, 89%, and 83% of patients, respectively, completed treatment. Baseline mean scores were 101.7 (PANSS total score) and 5.1 (CGI-S scale score). The mean difference ±standard error (SE) vs. placebo from baseline to Week 4 in PANSS score was −6.4±1.8 (P<.001) for the ALKS 3831 group and −5.3±1.8 (P=.004) for the olanzapine group. Mean difference ±SE vs. placebo from baseline to Week 4 in CGI-S scale score was −0.4±0.1 (P=.002) for the ALKS 3831 group and −0.4±0.1 (P<.001) for the olanzapine group. Overall, discontinuation due to AEs was low. Common AEs (≥5%) included weight gain, somnolence, dry mouth, anxiety, headache, and schizophrenia.

Conclusions: Treatment with ALKS 3831 resulted in greater antipsychotic efficacy compared with placebo, as measured by the PANSS and CGI-S scale, and was similar to the active control, olanzapine. The safety profile of ALKS 3831 was similar to olanzapine.