Long-Term Safety, Tolerability, and Durability of Treatment Effect of Olanzapine and Samidorphan: Results of a 4-Year Open-Label Study

J Clin Psychiatry. 2024 Dec 4;86(1):24m15511. doi: 10.4088/JCP.24m15511.

Abstract

Objective: Evaluate long-term safety, tolerability, and durability of the effect of olanzapine/samidorphan (OLZ/SAM) for up to 4 years in patients with schizophrenia, schizophreniform disorder, or bipolar I disorder (BD-I).

Methods: This phase 3, multicenter, open-label, long-term extension (conducted June 2017-September 2023) assessed OLZ/SAM in patients completing the ENLIGHTEN clinical program. Patients received ≥2-4 years of additional treatment. Safety assessments included adverse event (AE) incidences and changes from baseline in body weight, waist circumference, and lipid/glycemic parameters. The durability of the effect was assessed using the Clinical Global Impressions-Severity (CGI-S) scale.

Results: Of 524 patients enrolled, 523 received ≥1 dose of OLZ/SAM. Of these, 460 (88%) patients had schizophrenia, 15 (3%) had schizophreniform disorder, and 48 (9%) had BD-I. Mean (SD) age was 35.1 (12.2) years. Mean (SD) OLZ/SAM exposure was 652.4 (454.8) days. Of 451 patients eligible for 2 years of treatment, 242 (53.7%) received it; of 335 patients eligible for 4 years, 109 (32.5%) received it. 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, mean (SD) body weight change was 0.84 (6.84) kg; waist circumference change was -0.56 (6.24) cm. At 4 years, mean (SD) body weight change was 2.65 (8.12) kg; waist circumference change was 1.37 (8.65) cm. Changes in lipid/glycemic parameters were minimal. CGI-S scores remained stable.

Conclusion: OLZ/SAM maintained symptom control with a long-term safety profile over 4 years consistent with that of prior studies.

Trials Registration: ClinicalTrials.gov identifier: NCT03201757.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase III

MeSH terms

  • Adult
  • Antipsychotic Agents* / administration & dosage
  • Antipsychotic Agents* / adverse effects
  • Antipsychotic Agents* / pharmacology
  • Antipsychotic Agents* / therapeutic use
  • Bipolar Disorder* / drug therapy
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Naltrexone / analogs & derivatives
  • Olanzapine* / adverse effects
  • Olanzapine* / therapeutic use
  • Psychotic Disorders / drug therapy
  • Schizophrenia* / drug therapy
  • Treatment Outcome
  • Waist Circumference / drug effects
  • Young Adult

Substances

  • Olanzapine
  • Antipsychotic Agents
  • 3-carboxamido-4-hydroxynaltrexone
  • Drug Combinations
  • Naltrexone

Associated data

  • ClinicalTrials.gov/NCT03201757