T24. A PHASE 3, MULTICENTER STUDY TO ASSESS THE LONG-TERM SAFETY, TOLERABILITY AND EFFICACY OF ALKS 3831 IN SUBJECTS WITH SCHIZOPHRENIA

ALKS 3831, currently under development for the treatment of schizophrenia, is composed of a flexible dose of olanzapine and a fixed dose of 10 mg of samidorphan. Samidorphan is intended to mitigate weight gain associated with olanzapine treatment alone. Here, we report the safety, tolerability and efficacy of ALKS 3831 in subjects with schizophrenia that were enrolled in a phase 3, 52 week open-label extension study. Subjects had completed a phase 3, 4-week, double-blind, inpatient acute efficacy study of ALKS 3831 compared to olanzapine or placebo. Subjects were switched from either ALKS 3831, olanzapine or placebo from the previous study to receive treatment with ALKS 3831 10/10 (10 mg olanzapine/10 mg samidorphan) as investigators were blinded to previous treatment. Subsequently, treatment could be increased to 15/10 or 20/10 at any time during the study at the discretion of the Investigator. Study assessments included adverse event monitoring, clinical laboratory testing, evaluation of extrapyramidal symptoms, PANSS and CGI-S rating scales (last observed on treatment visit), and weight (observed case). Sites were located in the United States, Ukraine, Serbia and Bulgaria. In total, 281 patients were enrolled in this extension study and 277 subjects received at least 1 dose of study drug with the majority of subjects being male (58.1%), a mean (SD) age of 41.4 (11.31) years, and white (78.7%). The baseline weight of all 277 subjects was 79.1 kg (SD=17.8 kg). A total of 183 (66.1%) subjects completed the treatment period. Overall, the most common reasons for early termination were withdrawal by subject (15.5%), lost to follow-up (6.9%) and adverse event (5.8%). 1.8% of subjects discontinued due to lack of efficacy. Treatment emergent adverse events (TEAEs) were reported in 136 (49.1%) subjects. Serious adverse events were reported in 8 (2.9%) subjects and none were considered related to study drug. No deaths were reported. Most of the TEAEs were mild in severity. The common TEAEs (≥4%) were weight increase (13%), somnolence (8%), nasopharyngitis (4%), and headache (4%). The mean weight increase from baseline was 2.79%. There was a statistically significant improvement in PANSS and CGI-S scores with a 14.0 (SE=1.11; p<0.001) and 0.8 (SE=0.07; p<0.001) point improvement from baseline scores of 78.9 (SD=16.51), and 3.9 (SD=1.00), respectively. ALKS 3831 was generally well tolerated with a safety profile that supports long-term effective treatment. Over the course of this 52-week study, there was a significant improvement in schizophrenia symptoms.