Black Jed, Pillar Giora, Hedner Jan, Polo Olli, Berkani Ouali, Mangialaio Sara, Hmissi Abdel, Zammit Gary, Hajak Goran
Center for Sleep Research and Medicine, Stanford, USA.
Rambam Medical Center, Haifa, Israel.
Sleep Med. 2017 Aug;36:86-94. doi: 10.1016/j.sleep.2017.05.009. Epub 2017 May 29.
The orally active dual OXR and OXR antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults.
Prospective, randomized, double-blind, placebo-controlled, active referenced trial in male and female adults aged 18-64 years with chronic, primary insomnia. Patients were randomized 1:1:1:1 to receive placebo, almorexant 100 mg, almorexant 200 mg, or zolpidem 10 mg (active reference) for 16 days. Primary efficacy assessments were objective (polysomnography-measured) and subjective (patient-recorded) wake time after sleep onset (WASO). Further sleep variables were also evaluated.
From 709 randomized patients, 707 (mean age 45.4 years; 61.7% female) received treatment and 663 (93.8%) completed the study. A significant decrease versus placebo in median objective WASO was observed with almorexant 200 mg at the start and end of randomized treatment (-26.8 min and -19.5 min, respectively; both p < 0.0001); subjective WASO also decreased over the two-week treatment period (p = 0.0006). Objective and subjective total sleep time (TST) were increased with almorexant 200 mg (p < 0.0001). Almorexant 200 mg significantly reduced objective and subjective latency to persistent sleep and latency to sleep onset at initiation of therapy, and provided longer duration of sleep stages with no suppression of slow-wave sleep. No impaired next-day performance, rebound insomnia, or withdrawal effects were observed. Adverse events were similar with almorexant and placebo.
Almorexant reduced time to sleep onset and maintained sleep without residual effects on next-day performance or safety concerns. This study provides further support for the role of the endogenous orexin system in insomnia disorder. CLINICALTRIALS.
NCT00608985.
口服活性双重食欲素受体（OXR）激动剂及拮抗剂阿莫雷生作用于食欲素系统，用于治疗原发性失眠。本临床试验评估了阿莫雷生对睡眠维持及其他睡眠终点指标的影响，及其在成人中的安全性和耐受性。
对年龄在18 - 64岁、患有慢性原发性失眠的成年男性和女性进行前瞻性、随机、双盲、安慰剂对照、活性药物对照试验。患者按1:1:1:1随机分组，接受安慰剂、100毫克阿莫雷生、200毫克阿莫雷生或10毫克唑吡坦（活性对照药物）治疗16天。主要疗效评估指标为睡眠起始后客观（多导睡眠图测量）和主观（患者记录）的清醒时间（WASO）。还评估了其他睡眠变量。
在709例随机分组的患者中，707例（平均年龄45.4岁；61.7%为女性）接受了治疗，663例（93.8%）完成了研究。在随机治疗开始和结束时，200毫克阿莫雷生组的客观WASO中位数与安慰剂相比显著降低（分别为 - 26.8分钟和 - 19.5分钟；均p < 0.0001）；在两周治疗期间主观WASO也有所下降（p = 0.0006）。200毫克阿莫雷生可增加客观和主观总睡眠时间（TST）（p < 0.0001）。200毫克阿莫雷生在治疗开始时显著缩短了客观和主观的持续睡眠潜伏期及睡眠起始潜伏期，并提供了更长的睡眠阶段持续时间，且未抑制慢波睡眠。未观察到次日表现受损、反弹性失眠或撤药效应。阿莫雷生组和安慰剂组的不良事件相似。
阿莫雷生缩短了入睡时间并维持了睡眠，对次日表现无残留影响，也无安全性问题。本研究为内源性食欲素系统在失眠症中的作用提供了进一步支持。临床试验。
NCT00608985。
