TY - JOUR
T1 - A phase 3, multicenter study to assess the 1-year safety and tolerability of a combination of olanzapine and samidorphan in patients with schizophrenia
T2 - Results from the ENLIGHTEN-2 long-term extension
AU - Kahn, René S
AU - Silverman, Bernard L
AU - DiPetrillo, Lauren
AU - Graham, Christine
AU - Jiang, Ying
AU - Yin, Jiani
AU - Simmons, Adam
AU - Bhupathi, Vasudev
AU - Yu, Bei
AU - Yagoda, Sergey
AU - Hopkinson, Craig
AU - McDonnell, David
N1 - Funding Information:
In this open-label study, OLZ/SAM was generally well tolerated in adults with schizophrenia who received treatment for up to 52 weeks. The tolerability of OLZ/SAM is supported by the overall study completion rate, the low rate of discontinuation attributable to AEs and the low incidence of SAEs. Long-term treatment with OLZ/SAM was associated with sustained antipsychotic efficacy and minimal effects on weight, waist circumference, and metabolic parameters over 52 weeks of treatment.
Funding Information:
This study was sponsored by Alkermes, Inc. Alkermes employees were involved in the study design; the collection, analysis, and interpretation of data; the review of the manuscript; and the decision to submit for publication.
Publisher Copyright:
© 2021 The Authors
PY - 2021/6
Y1 - 2021/6
N2 - AIM: A combination of olanzapine and samidorphan (OLZ/SAM) is in development for the treatment of patients with schizophrenia or bipolar I disorder and is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension (NCT02873208; ENLIGHTEN-2-EXT) assessed the long-term safety and tolerability of OLZ/SAM in patients with schizophrenia.METHODS: Patients completing the 24-week randomized, double-blind, phase 3 ENLIGHTEN-2 study (NCT02694328) comparing weight change from baseline to week 24 with OLZ/SAM versus olanzapine were eligible to enroll in the 52-week ENLIGHTEN-2-EXT study. Assessments included adverse events (AEs; each visit), weight/waist circumference (every other week for the first 8 weeks, then every 4 weeks thereafter), metabolic laboratory parameters (weeks 4, 12, 24, 36, and 52), Positive and Negative Syndrome Scale (PANSS) scores (weeks 2, 4, 8, 12, 24, 36, and 52), and Clinical Global Impression-Severity (CGI-S) scores (weeks 2 and 4, then every 4 weeks thereafter through week 48, and at week 52). Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.RESULTS: In total, 265 patients were enrolled and received at least 1 dose of OLZ/SAM; 167 (63.0%) completed the 52-week extension study. Common AEs (≥5%) were weight decreased (n = 23; 8.7%), extra dose administered (n = 21; 7.9%), headache (n = 18; 6.8%), and weight increased (n = 16; 6.0%). At week 52, the mean (SD) change from baseline for weight and waist circumference was -0.03 (6.17) kg and - 0.35 (6.12) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. During the extension, PANSS total scores remained stable, and at week 52, 81.3% of patients had CGI-S scores of 3 or less, reflecting mild illness severity.CONCLUSIONS: OLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.
AB - AIM: A combination of olanzapine and samidorphan (OLZ/SAM) is in development for the treatment of patients with schizophrenia or bipolar I disorder and is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension (NCT02873208; ENLIGHTEN-2-EXT) assessed the long-term safety and tolerability of OLZ/SAM in patients with schizophrenia.METHODS: Patients completing the 24-week randomized, double-blind, phase 3 ENLIGHTEN-2 study (NCT02694328) comparing weight change from baseline to week 24 with OLZ/SAM versus olanzapine were eligible to enroll in the 52-week ENLIGHTEN-2-EXT study. Assessments included adverse events (AEs; each visit), weight/waist circumference (every other week for the first 8 weeks, then every 4 weeks thereafter), metabolic laboratory parameters (weeks 4, 12, 24, 36, and 52), Positive and Negative Syndrome Scale (PANSS) scores (weeks 2, 4, 8, 12, 24, 36, and 52), and Clinical Global Impression-Severity (CGI-S) scores (weeks 2 and 4, then every 4 weeks thereafter through week 48, and at week 52). Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.RESULTS: In total, 265 patients were enrolled and received at least 1 dose of OLZ/SAM; 167 (63.0%) completed the 52-week extension study. Common AEs (≥5%) were weight decreased (n = 23; 8.7%), extra dose administered (n = 21; 7.9%), headache (n = 18; 6.8%), and weight increased (n = 16; 6.0%). At week 52, the mean (SD) change from baseline for weight and waist circumference was -0.03 (6.17) kg and - 0.35 (6.12) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. During the extension, PANSS total scores remained stable, and at week 52, 81.3% of patients had CGI-S scores of 3 or less, reflecting mild illness severity.CONCLUSIONS: OLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.
KW - Antipsychotic agents
KW - Clinical trial
KW - Outpatients
KW - Waist circumference
KW - Weight gain
UR - http://www.scopus.com/inward/record.url?scp=85106252312&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2021.04.009
DO - 10.1016/j.schres.2021.04.009
M3 - Article
C2 - 34015555
SN - 0920-9964
VL - 232
SP - 45
EP - 53
JO - Schizophrenia Research
JF - Schizophrenia Research
ER -