Olanzapine/Samidorphan Effects on Weight Gain: A Pooled Analysis of Phase 2 and 3 Randomized, Double-Blind Studies

This work was sponsored by Alkermes, Inc. BACKGROUND/OBJECTIVE: This post hoc analysis assessed weight change profiles of OLZ/SAM versus olanzapine. METHODS: Data from 3 randomized, double-blind studies (NCT01903837 [phase 2], NCT02694328 [phase 3], NCT03187769 [phase 3]) assessing weight change as a primary or secondary outcome for OLZ/SAM versus olanzapine in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) were pooled. Adults with SZ or BD-I who received daily OLZ/SAM (olanzapine 5-20 mg + samidorphan 10 mg) or olanzapine (5-20 mg) and had ≥1 postbaseline weight assessment by week 12 were included. The primary endpoint was percent change in body weight, and the secondary endpoints were proportions with ≥7% or ≥10% weight gain. Metabolic changes and adverse events (AEs) were also examined. RESULTS: Among 1336 randomized patients, 1063 (79.6%) meeting criteria were analyzed. Mean (SD) age was 35.2 (10.7), 308 (29%) were female, 440 (41.4%) were White, and mean (SD) BMI was 24.8 (3.3) kg/m2. At week 12, OLZ/SAM was associated with lower least-squares mean (LSM) percent change in body weight from baseline (3.68%) versus olanzapine (5.43%; LSM [SE] difference=−1.75% [0.41]; 95% CI=−2.55, −0.94). Fewer patients taking OLZ/SAM versus olanzapine gained ≥7% (23.9% vs 34.6%; odds ratio [OR]=0.58; 95% CI=0.43, 0.79) or ≥10% of baseline body weight (13.7% vs 20.4%; OR=0.60; 95% CI=0.42, 0.88). Metabolic parameters and AEs were similar between treatment groups at week 12. CONCLUSIONS: In this pooled post hoc analysis, treatment with OLZ/SAM was consistently associated with less weight gain and reduced odds of ≥7% or ≥10% weight gain at week 12 versus olanzapine.