Purpose

To assess the efficacy of tasimelteon to improve sleep in Smith–Magenis syndrome (SMS).

Methods

A 9-week, double-blind, randomized, two-period crossover study was conducted at four US clinical centers. Genetically confirmed patients with SMS, aged 3 to 39, with sleep complaints participated in the study. Patients were assigned to treatment with tasimelteon or placebo in a 4-week crossover study with a 1-week washout between treatments. Eligible patients participated in an open-label study and were followed for >3 months.

Results

Improvement of sleep quality (DDSQ50) and total sleep time (DDTST50) on the worst 50% of nights were primary endpoints. Secondary measures included actigraphy and behavioral parameters. Over three years, 52 patients were screened, and 25 patients completed the randomized portion of the study. DDSQ50 significantly improved over placebo (0.4, p = 0.0139), and DDTST50 also improved (18.5 minutes, p = 0.0556). Average sleep quality (0.3, p = 0.0155) and actigraphy-based total sleep time (21.1 minutes, p = 0.0134) improved significantly, consistent with the primary outcomes. Patients treated for ≥90 days in the open-label study showed persistent efficacy. Adverse events were similar between placebo and tasimelteon.

Conclusion

Tasimelteon safely and effectively improved sleep in SMS.

中文翻译：

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Tasimeleon 安全有效地改善 Smith-Magenis 综合征患者的睡眠：一项双盲随机试验，随后进行开放标签扩展

目的

评估他司美琼改善 Smith-Magenis 综合征 (SMS) 睡眠的功效。

方法

在四个美国临床中心进行了一项为期 9 周、双盲、随机、两期的交叉研究。年龄在 3 至 39 岁、有睡眠问题的经基因证实的 SMS 患者参与了这项研究。在一项为期 4 周的交叉研究中，患者被分配接受他司美琼或安慰剂治疗，治疗之间有 1 周的清除期。符合条件的患者参加了一项开放标签研究，并被随访 > 3 个月。

结果

在最差的 50% 的夜晚，睡眠质量 (DDSQ50) 和总睡眠时间 (DDTST50) 的改善是主要终点。次要测量包括活动记录和行为参数。三年多来，筛选了 52 名患者，其中 25 名患者完成了研究的随机部分。DDSQ50 比安慰剂显着改善（0.4，p  = 0.0139），DDTST50 也得到改善（18.5 分钟，p  = 0.0556）。平均睡眠质量（0.3，p  = 0.0155）和基于活动记录的总睡眠时间（21.1 分钟，p  = 0.0134）显着改善，与主要结果一致。在开放标签研究中治疗≥90天的患者显示出持续的疗效。安慰剂和他司美琼之间的不良事件相似。

结论

Tasimeleon 安全有效地改善短信中的睡眠。