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Psych Congress  

Olanzapine/Samidorphan for Schizophrenia: Weight Gain and Metabolic Outcomes in Phase 3 ENLIGHTEN-2 and Subsequent Long-Term, Open-Label Safety Study

Authors  

Christoph Correll, MD – Hofstra Northwell School of Medicine; John Newcomer, MD – Thriving Mind South Florida; Bernard Silverman, MD – Alkermes, Inc.; Lauren DiPetrillo, PhD – Alkermes, Inc.; Christine Graham, PhD – Alkermes, Inc.; Ying Jiang, PhD – Alkermes, Inc.; Yangchun Du, PhD – Alkermes, Inc.; Adam Simmons, MPH – Alkermes, Inc.; Craig Hopkinson, MD – Alkermes, Inc.; David McDonnell, MD – Alkermes Pharma Ireland Limited; Rene Kahn, MD, PhD – Icahn School of Medicine at Mount Sinai

Sponsor  
Alkermes, Inc.

BACKGROUND: Opioid antagonists may mitigate medication-associated weight gain and/or metabolic dysregulation. ENLIGHTEN-2 evaluated a combination of olanzapine and the opioid antagonist samidorphan (OLZ/SAM) vs olanzapine for effects on weight gain and metabolic parameters over 24 weeks in adults with stable schizophrenia.

METHODS: This phase 3, double-blind study (ClinicalTrials.gov: NCT02694328) enrolled adults 18‒55 yo with stable schizophrenia, randomized 1:1 to once-daily OLZ/SAM or olanzapine. Co-primary endpoints were percent change from baseline in body weight and proportion of patients with ≥10% weight gain at week 24. Waist circumference and fasting metabolic parameters were also measured. Completers could enter a 52-week open-label safety extension.

RESULTS: 561 patients were randomized: 550 were dosed, 538 had ≥1 post-baseline weight assessment, and 352 (64%) completed; 10.9% discontinued due to AEs. At week 24, least squares mean (SE) percent weight change from baseline was 4.21 (0.68)% with OLZ/SAM and 6.59 (0.67)% with olanzapine (difference, −2.38 [0.76]%; P=0.003). Fewer patients treated with OLZ/SAM (17.8%) had ≥10% weight gain vs olanzapine (29.8%; odds ratio=0.50; P=0.003). The change from baseline in waist circumference was significantly smaller with OLZ/SAM (P < 0.001). Common AEs (≥10%) with OLZ/SAM and olanzapine were weight increased (24.8%, 36.2%), somnolence (21.2%, 18.1%), dry mouth (12.8%, 8.0%), and increased appetite (10.9%, 12.3%), respectively. Metabolic parameter changes were generally small and remained stable with long-term OLZ/SAM treatment.

DISCUSSION: OLZ/SAM treatment limited weight gain associated with olanzapine. Metabolic parameter changes were generally small, similar between groups over 24 weeks, and remained stable over an additional 52 weeks of open-label OLZ/SAM treatment.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.

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