Merck & Co Inc, Whitehouse Station, NJ, USA.
Merck & Co Inc, Whitehouse Station, NJ, USA.
Lancet Neurol. 2014 May;13(5):461-71. doi: 10.1016/S1474-4422(14)70053-5. Epub 2014 Mar 27.
Suvorexant (MK-4305) is an orexin receptor antagonist shown to be efficacious for insomnia over 3 months. We aimed to assess its clinical profile during and after 1 year of treatment.
We did a randomised, placebo-controlled, parallel-group trial at 106 investigational centres in the Americas, Australia, Europe, and South Africa from December, 2009, to August, 2011. Patients aged 18 years or older with primary insomnia by DSM-IV-TR criteria were assigned using a computer-generated randomised allocation schedule to receive nightly suvorexant (40 mg for patients younger than 65 years, 30 mg for patients aged 65 years or older) or placebo at a 2:1 ratio for 1 year with a subsequent 2-month randomised discontinuation phase in which patients on suvorexant either continued suvorexant or were abruptly switched to placebo while patients on placebo remained on placebo. Treatment assignment was masked from patients and investigators. The primary objective was to assess the safety and tolerability of suvorexant for up to 1 year. Secondary objectives were to assess the efficacy of suvorexant for improving patient-reported subjective total sleep time (sTST) and time to sleep onset (sTSO) over the first month of treatment. Efficacy endpoints over the first month were assessed with a mixed model with terms for baseline value of the response variable, age, sex, region, treatment, time, and treatment by time interaction. This trial is registered with ClinicalTrials.gov, number NCT01021813.
322 (62%) of 522 patients randomly assigned to receive suvorexant and 162 (63%) of 259 assigned to receive placebo completed the 1-year phase. Over 1 year, 362 (69%) of 521 patients treated with suvorexant experienced any adverse events compared with 164 (64%) of 258 treated with placebo. Serious adverse events were recorded in 27 patients (5%) who received suvorexant and 17 (7%) who received placebo. The most common adverse event, somnolence, was reported for 69 patients (13%) who received suvorexant and seven (3%) who received placebo. At month 1, suvorexant (517 patients in the efficacy population) showed greater efficacy than placebo (254 in the efficacy population) in improving sTST (38·7 min vs 16·0 min; difference 22·7, 95% CI 16·4 to 29·0; p<0·0001) and sTSO (-18·0 min vs -8·4 min, difference -9·5, -14·6 to -4·5; p=0·0002).
Our findings show that suvorexant was generally safe and well tolerated over 1 year of nightly treatment in patients with insomnia, with efficacy noted for subjective measures of sleep onset and maintenance.
Merck & Co Inc.
苏沃雷生（MK-4305）是一种食欲素受体拮抗剂，已被证明对失眠症有 3 个月以上的疗效。我们旨在评估其在 1 年治疗期间和之后的临床特征。
我们在 2009 年 12 月至 2011 年 8 月期间在美洲、澳大利亚、欧洲和南非的 106 个研究中心进行了一项随机、安慰剂对照、平行组试验。根据 DSM-IV-TR 标准，年龄在 18 岁或以上的原发性失眠症患者被随机分配到每晚服用苏沃雷生（65 岁以下患者 40 毫克，65 岁以上患者 30 毫克）或安慰剂组，比例为 2:1，持续 1 年，随后是 2 个月的随机停药阶段，在此阶段，服用苏沃雷生的患者要么继续服用苏沃雷生，要么突然转为安慰剂，而服用安慰剂的患者继续服用安慰剂。治疗分配对患者和研究者均保密。主要目的是评估苏沃雷生在长达 1 年的时间内的安全性和耐受性。次要目的是评估苏沃雷生在改善患者报告的主观总睡眠时间（sTST）和入睡潜伏期（sTSO）方面的疗效，治疗时间为 1 个月。在第一个月内，使用具有反应变量基线值、年龄、性别、地区、治疗、时间和治疗与时间交互作用项的混合模型评估疗效终点。该试验在 ClinicalTrials.gov 上注册，编号为 NCT01021813。
322（62%）名随机分配接受苏沃雷生的 522 名患者和 162（63%）名随机分配接受安慰剂的 259 名患者完成了 1 年治疗期。在 1 年期间，362（69%）名接受苏沃雷生治疗的患者经历了任何不良事件，而 258 名接受安慰剂治疗的患者中 164 名（64%）经历了任何不良事件。27 名（5%）接受苏沃雷生治疗的患者和 17 名（7%）接受安慰剂治疗的患者出现严重不良事件。最常见的不良事件为思睡，接受苏沃雷生治疗的 69 名患者（13%）和接受安慰剂治疗的 7 名患者（3%）出现思睡。在第一个月，苏沃雷生（疗效人群中的 517 名患者）在改善 sTST（38.7 分钟 vs 16.0 分钟；差异 22.7，95%CI 16.4 至 29.0；p<0.0001）和 sTSO（-18.0 分钟 vs -8.4 分钟，差异-9.5，-14.6 至-4.5；p=0.0002）方面的疗效优于安慰剂（疗效人群中的 254 名患者）。
我们的研究结果表明，苏沃雷生在每晚治疗失眠症患者 1 年期间通常是安全且耐受良好的，并且在睡眠起始和维持的主观测量方面具有疗效。
默克公司。
