A phase 3, multicenter study to assess the long-term safety, tolerability, and efficacy of olanzapine/samidorphan in patients with schizophrenia

Background: ALKS 3831, a combination of olanzapine and samidorphan (OLZ/SAM), is in development for the treatment of schizophrenia and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. We report the safety, tolerability, and efficacy of OLZ/SAM in patients with schizophrenia in a phase 3, 52-week, open-label extension study. METHODS: Patients aged 18-70 years who completed a previous phase 3, 4-week, inpatient acute efficacy study were switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Study assessments included adverse events (AEs), weight, clinical laboratory testing, and Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S) scores. RESULTS: 281 patients were enrolled; 277 (mean age, 41.4 years) received >1 dose of study drug, and 183 (66.1%) completed the extension study. The most common reasons for discontinuation were withdrawal by patient (15.5%), loss to follow-up (6.9%), andAEs (5.8%). AEs were reported in 136 (49.1%) patients; mostweremildin severity. The most common AEs were increased weight (13.4%), somnolence (8.3%), nasopharyngitis (4.0%), and headache (4.0%). Mean weight increase from baseline in patients completing 52 weeks of treatment was 1.86 kg, a 2.79% increase. No clinically significant changes in mean laboratory parameters were observed. Mean (SD) changes from baseline to week 52 in PANSS total score and CGI-S score were -16.2 (15.41) and -0.9 (0.92), respectively (both P<0.001). N: OLZ/SAM was generally well tolerated with a safety profile that supports long-term treatment. During this 52-week extension study, there were improvements in schizophrenia symptoms.