Long-Term Safety and Efficacy of Olanzapine/Samidorphan: Results of a 4-Year Open-Label Study
INTRODUCTION: 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 diagnosed schizophrenia/schizophreniform disorder (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.
