Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study.

Abstract

BACKGROUND:

Combination olanzapine and samidorphan (OLZ/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported.

METHODS:

Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Assessments included adverse events (AEs), weight, vital signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ/SAM in the extension study.

RESULTS:

In total, 281 patients enrolled, 277 received ≥1 OLZ/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported in eight patients (2.9%); none were considered treatment related. There were no deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 52: -16.2 [-18.5, -14.0] and -0.9 [-1.0, -0.8], respectively).

CONCLUSION:

OLZ/SAM was generally well tolerated in this extension study; most patients completed the 52-week treatment period with sustained improvement in schizophrenia symptoms. Mean increases in weight stabilized by week 6 with limited subsequent change through end of treatment.

• Authors: Sergey Yagoda, Christine Graham, Adam Simmons, Christina Arevalo, Ying Jiang, David McDonnell
• Journal: CNS spectrums (CNS Spectr) Vol. 26 Issue 4 Pg. 383-392 (08 2021) ISSN: 1092-8529 [Print] United States
• PMID: 32393412 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adult
• Antipsychotic Agents (therapeutic use)
• Drug Therapy, Combination
• Female
• Humans
• Male
• Middle Aged
• Naltrexone (analogs & derivatives, therapeutic use)
• Olanzapine (therapeutic use)
• Schizophrenia (drug therapy)
• Treatment Outcome