BackgroundCombination 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.MethodsPatients 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.ResultsIn 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).ConclusionOLZ/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.

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长期安全性和持久性：一项为期 1 年的开放标签扩展研究的结果

背景奥氮平和沙米多芬联合用药 (OLZ/SAM) 正在开发用于治疗精神分裂症和双相 I 型障碍，旨在提供奥氮平的疗效，同时减轻奥氮平相关的体重增加。报道了一项针对精神分裂症患者进行的为期 52 周的开放标签扩展研究的 OLZ/SAM 安全性、耐受性和有效性。安慰剂对 OLZ/SAM。评估包括不良事件 (AE)、体重、生命体征、阳性和阴性症状量表 (PANSS) 和临床总体印象严重程度 (CGI-S) 评分。基线是在扩展研究中首次给药 OLZ/SAM 之前。结果总共有 281 名患者入组，277 名接受 ≥1 次 OLZ/SAM 剂量，183 名 (66.1%) 完成了 52 周。停药的原因包括患者退出（15.5%）、失访（6.9%）、不良事件（5.8%）和缺乏疗效（1.8%）。136 名 (49.1%) 患者报告了 AE；体重增加（13%）和嗜睡（8%）是最常见的。8 名患者（2.9%）报告了 10 次严重 AE；没有一个被认为与治疗有关。没有死亡。平均 (SD) 基线体重为 79.1 (17.8) 公斤。从基线到第 52 周的平均体重变化为 1.86 kg（增加 2.79%）。PANSS 总分和 CGI​​-S 分数在 52 周内持续下降（平均 [95% CI] 从基线到第 52 周的变化：分别为 -16.2 [-18.5, -14.0] 和 -0.9 [-1.0, -0.8]）。结论 OLZ/SAM 在本次扩展研究中总体耐受性良好；大多数患者完成了 52 周的治疗期，精神分裂症症状持续改善。