Summary of Change in Latency to Persistent Sleep.

Background
Tasimelteon is a dual melatonin 1 and melatonin 2  receptor agonist. Tasimelteon is the first and only approved medicine to treat a circadian rhythm disorder. In this Phase III trial, the efficacy and safety of tasimelteon was studied in primary insomnia characterized by difficulty falling asleep.
Trial design
A randomized, double-blind, placebo-controlled, multi-center study investigated 20 mg or 50 mg tasimelteon vs placebo in 322 patients with primary insomnia over a 5-week double-blind treatment interval using polysomnography(PSG) measures of sleep.
Methods
Patients underwent PSGs on Nights 1, 8, 22 and 29. Entry criteria emphasized enrollment of primary insomnia patients with a confirmed difficulty falling asleep. Subjective sleep latency was ≥ 45 minutes based on sleep history and sleep diary and, patients had a mean latency to persistent sleep (LPS) of ≥30 minutes on two consecutive screening PSG nights with no night having an LPS less than 20 minutes.
Findings
On the primary end point, the mean improvement in LPS from baseline to the average of Nights 1 and 8 was 44.9 minutes (20 mg) and 46.3 minutes (50 mg) versus 28.2 minutes (placebo) (p < 0.001). Improvements in LPS persisted through the follow-up time points (Nights 22 and 29, p < 0.01). Tasimelteon use was not associated with cognitive or mood changes, and neither rebound nor withdrawal effects were observed after discontinuation.
Conclusion
Tasimelteon improved sleep from the first night of treatment, and the effect continued for the duration of the study. Tasimelteon was well-tolerated with no adverse next-day residual effects observed. The results of the study strongly suggest that tasimelteon may be an effective therapeutic tool in the treatment of individuals with chronic sleep onset insomnia.

背景
他司美琼（Tasimelteon）是双重褪黑素1型与褪黑素2型受体激动剂，亦是首款且唯一获批用于治疗昼夜节律紊乱的药物。本项III期临床试验针对入睡困难型原发性失眠患者，评估他司美琼的疗效与安全性。

试验设计
本研究为随机、双盲、安慰剂对照的多中心试验，共纳入322名原发性失眠患者，在为期5周的双盲治疗周期内，采用多导睡眠图（polysomnography, PSG）评估睡眠指标，对比20mg、50mg他司美琼与安慰剂的疗效差异。

研究方法
受试者分别于第1、8、22、29晚接受多导睡眠图检测。入组标准明确纳入经确诊的入睡困难型原发性失眠患者：基于睡眠史与睡眠日记，受试者的主观睡眠潜伏期≥45分钟；且在连续两晚的筛选期多导睡眠图检测中，其平均维持睡眠潜伏期（latency to persistent sleep, LPS）≥30分钟，且单晚维持睡眠潜伏期均不低于20分钟。

研究结果
主要终点方面，从基线至第1、8晚平均值的维持睡眠潜伏期改善均值：20mg组为44.9分钟，50mg组为46.3分钟，安慰剂组为28.2分钟（p<0.001）。维持睡眠潜伏期的改善效应持续至随访时间点（第22、29晚，p<0.01）。服用他司美琼未出现认知或情绪相关变化，停药后亦未观察到反跳性失眠或戒断反应。

结论
他司美琼自治疗首日即可改善睡眠，且该效应贯穿整个研究周期。他司美琼耐受性良好，未观察到次日残留不良反应。本研究结果强烈提示，他司美琼或可作为慢性入睡型失眠患者的有效治疗手段。