Olanzapine/Samidorphan in Young Adults With Schizophrenia, Schizophreniform Disorder, or Bipolar I Disorder Who Are Early in Illness: Results of the ENLIGHTEN-Early Study

Abstract: Aims: This 12-week, phase 3, multicenter, double-blind study (NCT03187769) evaluated the effect of combination olanzapine and samidorphan (OLZ/SAM) vs olanzapine on weight in early-in-illness patients with schizophrenia, schizophreniform disorder, or bipolar I disorder (BD-I). Methods: Patients 16-39 years old with < 4 years since symptom onset, BMI < 30 kg/m2, and < 24 weeks of cumulative antipsychotic exposure were randomized 1:1 to OLZ/SAM (olanzapine 5-20 mg/d + samidorphan 10 mg/d) or olanzapine (5-20 mg/d) for ≤12 weeks. The primary endpoint was percent change from baseline body weight at 12 weeks. Key secondary endpoints (week 12) were proportion of patients with ≥10% or ≥7% weight gain, change in waist circumference, and change in Clinical Global Impressions-Severity (CGI-S) score. Results: Of 428 patients (OLZ/SAM, n=213; olanzapine, n=215), 408 had ≥1 postbaseline weight assessment and were included in the analysis. Percent weight change at week 12 was significantly lower with OLZ/SAM (4.91%) vs olanzapine (6.77%) (least-squares mean [LSM] [SE] difference, −1.87% [0.745]; P=0.012). Although not statistically significant, fewer patients had ≥10% (21.9% vs 30.4%; OR=0.64; 95% CI=0.39-1.05) or ≥7% (33.1% vs 44.8%; OR=0.61; 95% CI=0.39-0.94) weight gain with OLZ/SAM vs olanzapine, respectively. Waist circumference change (OLZ/SAM: 2.99 cm; olanzapine: 3.90 cm) numerically favored OLZ/SAM (LSM [SE] difference, −0.92 cm [0.582], 95% CI=−2.06-0.22). OLZ/SAM treatment improved clinical symptoms (LSM [SE] change in CGI-S, −0.82 [0.06]). The safety profiles of OLZ/SAM and olanzapine were similar. Conclusion: Treatment with OLZ/SAM mitigated weight gain vs olanzapine in early-in-illness patients with schizophrenia, schizophreniform disorder, or BD-I.Short Description: ENLIGHTEN-Early was a 12-week, phase 3, multicenter, double-blind study evaluating the effects of combination olanzapine and samidorphan (OLZ/SAM) versus olanzapine in early-in-illness patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. Percent weight change from baseline at week 12 was significantly lower with OLZ/SAM.Name of Sponsoring Organization(s): This study was funded by Alkermes, Inc. Medical writing and editorial support were provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Alkermes, Inc.