ObjectiveCombination olanzapine and samidorphan (OLZ/SAM) is in development for treatment of schizophrenia and bipolar I disorder and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension study (NCT02873208; ENLIGHTEN-2-EXT) in schizophrenia assessed the safety and tolerability of OLZ/SAM. Methods: Patients completing the 24-week, randomized, double-blind, phase 3 ENLIGHTEN−2 study comparing weight gain with OLZ/SAM vs olanzapine were eligible for ENLIGHTEN-2-EXT enrollment. Initial OLZ/SAM doses were based on olanzapine dose (10 or 20 mg) received at the conclusion of ENLIGHTEN-2; subsequent olanzapine dose adjustments were allowed. The samidorphan dose (10 mg) remained fixed throughout. Assessments included adverse events (AEs), weight, waist circumference, metabolic laboratory parameters, and Positive and Negative Syndrome Scale (PANSS) scores. Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study.Results265 patients received OLZ/SAM; 167 (63.0%) completed the 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, mean (SD) change from baseline for weight and waist circumference was −0.03 (6.216) kg and −0.35 (6.115) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. PANSS total scores remained stable during the extension.ConclusionsOLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.FundingAlkermes, Inc.

中文翻译：

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奥氮平和沙米多芬联合治疗精神分裂症患者的 3 期安全性和耐受性结果：1 年 ENLIGHTEN-2-Extension

目标联合奥氮平和沙米多芬 (OLZ/SAM) 正在开发用于治疗精神分裂症和双相 I 型障碍，旨在提供奥氮平的抗精神病功效，同时减轻奥氮平相关的体重增加。这项针对精神分裂症的 52 周开放标签扩展研究 (NCT02873208; ENLIGHTEN-2-EXT) 评估了 OLZ/SAM 的安全性和耐受性。方法：完成 24 周、随机、双盲、3 期 ENLIGHTEN-2 研究比较体重增加与 OLZ/SAM 与奥氮平的患者有资格参加 ENLIGHTEN-2-EXT。初始 OLZ/SAM 剂量基于 ENLIGHTEN-2 结束时收到的奥氮平剂量（10 或 20 mg）；随后的奥氮平剂量调整是允许的。沙米多芬剂量 (10 mg) 自始至终保持固定。评估包括不良事件 (AE)、体重、腰围、代谢实验室参数和阳性和阴性症状量表 (PANSS) 评分。分析基于使用描述性统计观察到的结果。基线相对于扩展研究中的第一个 OLZ/SAM 剂量。结果 265 名患者接受了 OLZ/SAM；167 (63.0%) 人完成了扩展研究。常见的 AE (= 5%) 是体重减轻 (n=23; 8.7%)、给予额外剂量 (n=21; 7.9%)、头痛 (n=18; 6.8%) 和体重增加 (n=16; 6.0 %）。在第 52 周，体重和腰围从基线的平均 (SD) 变化分别为 -0.03 (6.216) kg 和 -0.35 (6.115) cm。空腹血脂和血糖参数的变化通常很小，并且在 52 周内保持稳定。PANSS总分在延长期间保持稳定。结论OLZ/SAM在52周内总体耐受良好。重量，