(#49) Safety, Tolerability, and Durability of Treatment Effect of Olanzapine and Samidorphan: A Patient Subgroup Analysis of a 4-Year Open-Label Study

Abstract: Objective: To analyze subgroup data from a 4-year, open-label study of combined olanzapine and samidorphan (OLZ/SAM) in adults with schizophrenia, schizophreniform disorder, or bipolar I disorder. Methods: Patients completing studies in the ENLIGHTEN clinical trial program were eligible to receive ?2ñ4 years of additional treatment in a phase 3, open-label study assessing OLZ/SAMís safety, tolerability, and durability of treatment effect. Prespecified subgroup analyses were conducted by age (18ñ29 or ?30 years), sex (male or female), race (Black/African American or non-Black/African American), baseline body mass index (BMI; 25 or ?25 kg/m2), and geographic region (US or non-US). Safety assessments included changes from baseline in body weight and waist circumference and adverse event (AE) incidences. Durability of treatment effect was assessed using the Clinical Global ImpressionsñSeverity (CGI-S) scale. Results: Overall, 523 patients were included; 53.7% (242/451) and 32.5% (109/335) received 2 and 4 years of treatment, respectively. At 2 years, OLZ/SAM treatment was associated with small mean changes from baseline in body weight (range: 0ñ2.15 kg) and minimal mean changes from baseline in waist circumference (range: ?1.13ñ0.15 cm) across subgroups. Mean changes in body weight (range: 1.51ñ5.49 kg) and waist circumference (range: 0.67ñ3.85 cm) were generally similar across subgroups at 4 years. No clinically meaningful subgroup differences in AEs were observed. Mean CGI-S scale scores were stable across subgroups at 2 and 4 years. Conclusions: Outcomes following up to 4 years of OLZ/SAM treatment were generally similar across age, sex, race, BMI, and geographic subgroups.Short Description: We analyzed subgroup data from a 4-year open-label study of combined olanzapine and samidorphan (OLZ/SAM) in patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. Prespecified analyses were conducted by age, sex, race, body mass index, and geographic region. After up to 4 years of treatment, OLZ/SAM was associated with small changes in body weight and waist circumference across subgroups. No meaningful subgroup differences in adverse events were observed. Across subgroups, symptom control was maintained.Name of Sponsoring Organization(s): This study was sponsored by Alkermes, Inc. Medical writing and editorial support were provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Alkermes, Inc.