S226. A STUDY COMPARING WEIGHT GAIN FROM ALKS 3831 TO OLANZAPINE IN EARLY-ILLNESS YOUNG ADULTS WITH SCHIZOPHRENIFORM, SCHIZOPHRENIA, OR BIPOLAR I DISORDER

Abstract

Background: First-and early-episode schizophrenia and bipolar I disorder are critical phases of the diseases where optimal pharmacologic efficacy is crucial. Olanzapine is a highly efficacious antipsychotic indicated for the treatment of schizo phrenia and bipolar I disorder [1]. However, the clinical utility of olanzapine is limited by a propensity to cause significant weight gain and metabolic risk, especially for patients early in the course of their illness who could benefit most from its antipsychotic efficacy. ALKS 3831 is a fixed-dose combination of olanzapine and samidorphan that has been shown in Phase 1 and Phase 2 studies to result in significantly less weight gain than olanzapine while delivering equivalent antipsychotic efficacy. The planned Phase 3, 12-week study, is designed to evaluate the effect of ALKS 3831 on body weight in young adults with schizophrenia, schizophreniform or bipolar I disorder who are early in their illness. Methods:The proposed study is an international (Austria, Germany, Ireland, Israel, Italy, Poland, Spain, United Kingdom, United States) two-arm, double-blind, active comparator con trolled, multi-center study (planned N = 250) that is slated to begin enrollment in 2017. Inclusion criteria are having a primary diagnosis of schizophrenia, schizophreniform disorder, or bipolar I disorder, a body-mass index (BMI) of > 18.0 and < 27.0 kg/m2 at Screening and randomization, and meet specific duration criteria for duration of illness and prior antipsychotic exposure. Subjects with bipolar I disorder must be experiencing an acute episode of mania. In addition, for US sites, men and women must be > 16 through < 40 years of age at Screening, and for European sites, men and women must be > 18 through < 40 years of age at Screening. Exclusion criteria include diagnosis of additional psychiatric conditions, use of prohibited or contraindicated drugs and abnormal lab results during screening. After up to a 4-week screening period, subjects will be randomized 1:1 to either olanzapine or ALKS 3831 treatment for 12 weeks. ALKS 3831 and olanzapine will be provided as bilayer tablets to be taken by mouth once daily and doses will include ALKS 3831 5/10 mg, 10/10 mg, 15/10 mg, 20/10 mg (olanzapine/samidorphan) or 5 mg, 10 mg or 15 mg olanzapine. The primary endpoint will be percent change from baseline in body weight at week 12. Secondary and exploratory endpoints will include weight gain thresholds, metabolic parameters (including fasting triglycerides, cholesterol, and glucose), bio impedance, and psychiatric symptoms will be evaluated. Safety, pharmacoki-netic, and pharmacodynamic parameters will also be measured. A daily medication adherence monitoring and reminder system (via smartphones) may be used in this study and subjects will be asked to participate in a supportive clinical care (SCC) program during the 12-week treatment period.