Eisai Inc, Woodcliff Lake, New Jersey.
Community Research Inc, Cincinnati, Ohio.
J Clin Sleep Med. 2017 Nov 15;13(11):1289-1299. doi: 10.5664/jcsm.6800.
To identify dose(s) of lemborexant that maximize insomnia treatment efficacy while minimizing next-morning residual sleepiness and evaluate lemborexant effects on polysomnography (PSG) measures (sleep efficiency [SE], latency to persistent sleep [LPS], and wake after sleep onset [WASO]) at the beginning and end of treatment.
Adults and elderly subjects with insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition were enrolled in a multicenter, randomized, double-blind, placebo-controlled, Bayesian, adaptive, parallel-group study, receiving lemborexant (1, 2.5, 5, 10, 15, 25 mg) or placebo for 15 nights. Efficacy assessments included a utility function that combined efficacy (SE) and safety (residual morning sleepiness as measured by Karolinska Sleepiness Scale [KSS]), PSG measures, and sleep diary. Safety assessments included KSS, Digit Symbol Substitution Test, computerized reaction time tests, and adverse events (AEs).
A total of 616 subjects were screened; 291 were randomized. Baseline characteristics were similar between lemborexant groups and placebo (∼63% female, median age: 49.0 years). The study was stopped for early success after the fifth interim analysis when the 15-mg dose met utility index/KSS criteria for success; 3 other doses also met the criteria. Compared with placebo, subjects showed significant improvements in SE, subjective SE, LPS, and subjective sleep onset latency at the beginning and end of treatment for lemborexant doses ≥ 5 mg ( < .05). WASO and subjective WASO showed numerically greater improvements for doses > 1 mg. AEs, mostly mild to moderate, included dose-related somnolence.
Lemborexant doses ranging from 2.5-10 mg provided efficacy for the treatment of insomnia while minimizing next-morning residual sleepiness.
Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia; URL: https://clinicaltrials.gov/ct2/show/NCT01995838; Identifier: NCT01995838.
确定最大限度提高失眠治疗效果，同时最小化次日残余嗜睡的利马曲班剂量，并评估利马曲班对治疗开始和结束时多导睡眠图（PSG）测量值（睡眠效率[SE]、持续睡眠潜伏期[LPS]和睡眠起始后觉醒[WASO]）的影响。
根据《精神障碍诊断与统计手册》第五版，患有失眠症的成年人和老年人被纳入一项多中心、随机、双盲、安慰剂对照、贝叶斯、适应性、平行组研究，接受利马曲班（1、2.5、5、10、15、25mg）或安慰剂治疗 15 晚。疗效评估包括一个效用函数，该函数结合了疗效（SE）和安全性（以 Karolinska 睡眠量表[KSS]测量的残余晨睡）、PSG 测量值和睡眠日记。安全性评估包括 KSS、数字符号替代测试、计算机反应时间测试和不良事件（AE）。
共有 616 名受试者接受了筛选，291 名被随机分组。利马曲班组和安慰剂组的基线特征相似（~63%为女性，中位年龄：49.0 岁）。在第五次中期分析后，由于 15mg 剂量符合效用指数/KSS 成功标准，该研究提前成功停止；其他 3 个剂量也符合标准。与安慰剂相比，利马曲班剂量≥5mg 的受试者在治疗开始和结束时 SE、主观 SE、LPS 和主观入睡潜伏期均有显著改善（<.05）。WASO 和主观 WASO 显示剂量>1mg 时的改善程度更大。不良事件（AE）主要为轻度至中度，包括与剂量相关的嗜睡。
利马曲班剂量为 2.5-10mg 可有效治疗失眠，同时最小化次日残余嗜睡。
标题：一项多中心、随机、双盲、安慰剂对照、平行组、贝叶斯适应性随机设计、E2006 对慢性失眠成人和老年人疗效的剂量反应研究；网址：https://clinicaltrials.gov/ct2/show/NCT01995838；标识符：NCT01995838。
