Thomas Dahl, PO Box 404, Guilford, CT 06437 USA. Email: tadahl@outlook.com. The objectives of the study were to demonstrate the efficacy and safety of SM-1 in a circadian challenge model of transient insomnia. Randomized, double-blind, placebo-controlled cross-over study utilizing a 5-h phase advance model of transient insomnia. Subjects were 85 healthy adults reporting a history of transient insomnia, with an average age of 38.9 years. Both SM-1 and placebo were administered to all subjects in a randomly assigned sequence, with at least 1 week between treatments. The primary endpoint was total sleep time determined by polysomnography. Secondary endpoints included wakefulness after sleep onset, latency to persistent sleep, number of awakenings, subjective total sleep time and subjective sleep onset latency, total sleep time by quarters of the night, subjective number of awakenings, and sleep quality. Safety endpoints included adverse events, Karolinska Sleepiness Scale, Digit Symbol Substitution Test, and predischarge evaluation (tandem gait and Romberg tests). SM-1 provided an increase of 94.4 min in total sleep time over placebo (p < 0.0001). Wakefulness after sleep onset, subjective total sleep time, subjective sleep onset latency, and total sleep time in the first quarter of the night also showed significant improvement. SM-1 was well-tolerated with both type and frequency of adverse events being comparable to placebo, and no residual sleepiness upon awakening (i.e., after 8 h). SM-1 provided a robust and statistically significant increase in total sleep time compared to placebo in a circadian model of transient insomnia, without evidence of next-day impairment.

Thomas Dahl，邮政信箱 404，吉尔福德，康涅狄格州 06437 美国。电子邮件：tadahl@outlook.com。该研究的目的是证明 SM-1 在短暂性失眠的昼夜节律挑战模型中的有效性和安全性。随机、双盲、安慰剂对照的交叉研究，利用短暂性失眠的 5 小时相位提前模型。受试者是 85 名报告有短暂失眠史的健康成年人，平均年龄为 38.9 岁。SM-1 和安慰剂均以随机分配的顺序对所有受试者给药，两次治疗之间至少间隔 1 周。主要终点是由多导睡眠图确定的总睡眠时间。次要终点包括入睡后觉醒、持续睡眠潜伏期、觉醒次数、主观总睡眠时间和主观入睡潜伏期，每季度的总睡眠时间、主观觉醒次数和睡眠质量。安全终点包括不良事件、Karolinska 嗜睡量表、数字符号替代测试和出院前评估（串联步态和 Romberg 测试）。与安慰剂相比，SM-1 的总睡眠时间增加了 94.4 分钟（p  < 0.0001)。入睡后觉醒、主观总睡眠时间、主观入睡潜伏期和第一季度总睡眠时间也有显着改善。SM-1 耐受性良好，不良事件的类型和频率与安慰剂相当，并且在醒来时（即 8 小时后）没有残留的困倦。在短暂性失眠的昼夜节律模型中，与安慰剂相比，SM-1 在总睡眠时间方面提供了稳健且统计上显着的增加，而没有第二天受损的证据。