Long-Term Safety and Efficacy of Olanzapine/Samidorphan: Results of a 4-Year Open-Label Study

Abstract: Background: Long-term safety, tolerability, and durability of therapeutic effect are important aspects of antipsychotic treatment. Methods: This phase 3, multicenter, open-label, long-term extension assessed the safety and efficacy of combination olanzapine/samidorphan (OLZ/SAM) treatment in patients who completed the ENLIGHTEN clinical trial program. Patients could receive ≥2 to 4 years of additional treatment. Safety assessments included adverse event (AE) incidences and changes from baseline in body weight, waist circumference, and lipid/glycemic parameters. Durability of effect was assessed using the Clinical Global Impressions-Severity (CGI-S) scale. Results: Of 524 patients enrolled, 523 received ≥1 dose of OLZ/SAM. Most patients had schizophrenia/schizophreniform disorder diagnoses (91%); the remainder had bipolar I disorder (9%). Mean (SD) age was 35.1 (12.2) years. Mean (SD) OLZ/SAM exposure was 652.4 (454.8) days. The most common AEs were weight increased (9.8%), headache (7.1%), anxiety (6.1%), insomnia (5.9%), somnolence (5.9%), nausea (5.7%), and weight decreased (5.7%). At 2 years (n=238/451 eligible patients), mean (SD) change in body weight was 0.84 (6.8) kg; waist circumference change was −0.56 (6.2) cm. At 4 years (n=108/335 eligible patients), mean (SD) change in body weight was 2.65 (8.1) kg; waist circumference change was 1.37 (8.7) cm. Changes in lipid and glycemic parameters were minimal. CGI-S scores remained stable with reductions of −0.18 (0.67) at 2 years and −0.24 (0.65) at 4 years. Conclusions: OLZ/SAM maintained symptom control with a long-term safety profile over 4 years consistent with prior studies, highlighting its clinical benefits as a maintenance treatment in patients with schizophrenia or bipolar I disorder.Short Description: This open-label extension study evaluated the long-term safety, tolerability, and durability of effect of OLZ/SAM in patients with schizophrenia, schizophreniform disorder, or bipolar I disorder who received ≥2 to 4 years of treatment. Treatment with OLZ/SAM resulted in a safety profile consistent with previous studies, with small changes in body weight and minimal changes in waist circumference and lipid and glycemic parameters while also maintaining symptom control.Name of Sponsoring Organization(s): Alkermes, Inc.