Study Retention Rates in the OLZ/SAM Phase III Clinical Program

INTRODUCTION: Efficacy and safety of the combination of olanzapine and samidorphan (OLZ/SAM) were assessed in 6 phase 3 studies of adults with schizophrenia or bipolar I disorder. We reviewed retention rates across these studies.
METHODS: Patients in 3 randomized controlled trials (RCTs) of 1mo, 3mo, or 6mo duration had the option to continue into two 1yr open-label extensions and one 4yr open-label study. Demographics and clinical characteristics were summarized. Proportions of patients completing the treatment period and reasons for study discontinuation were assessed descriptively for each study.
RESULTS: In the RCTs, 134, 211, and 274 patients received ≥1 dose of OLZ/SAM, whereas 277 and 265 in the 1yr extensions and 523 in the 3mo study or the 1yr extensions who continued into the 4y open-label study did so. Proportions of patients who completed the OLZ/SAM treatment period were 91.0% (122/134, 1mo), 78.2% (165/211, 3mo), 64.2% (176/274, 6mo), 66.1% (183/277, 1yr), and 63.0% (167/265, 1yr). In the 4yr open-label study, retention rates were 53.7% (242/451) at 2 years and 32.5% (109/335) at 4 years. Withdrawal by subject was the most common reason for discontinuation from each study (6.0% [8/134, 1mo]; 9.5% [20/211, 3mo]; 15.5% [43/277, 1yr]; 13.6% [36/265, 1yr]; 25.4% [133/523, 4yr]), except the 6mo trial (adverse event, 12.0% [33/274]).
CONCLUSIONS: Across the OLZ/SAM phase 3 clinical program, retention rates were high. Overall, 70% of dosed patients completed studies ≤1yr in duration, whereas retention rates were 54% at 2 years and 33% at 4 years in the 4yr open-label study.