Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial

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• 作者：Dr David Michelson ; MD^a ; ^{david_michelson@merck.com" class="auth_mail} ; Ellen Snyder ; PhD^a ; Erin Paradis ; BSN^a ; Mary Chengan-Liu ; PhD^a ; Duane B Snavely ; MA^a ; Jill Hutzelmann ; MS^a ; James K Walsh ; PhD^b ; Andrew D Krystal ; MD^c ; Ruth M Benca ; MD^d ; Martin Cohn ; MD^e ; Christopher Lines ; PhD^a ; Thomas Roth ; PhD^f ; W Joseph Herring ; MD^a
• 刊名：Lancet Neurology
• 出版年：May, 2014
• 年：2014
• 卷：13
• 期：5
• 页码：461-471
• 全文大小：242 K

文摘

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Summary

Background

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.

Methods

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 , number .

Findings

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路7 min vs 16路0 min; difference 22路7, 95% CI 16路4 to 29路0; p<0路0001) and sTSO (-18路0 min vs 鈭?路4 min, difference 鈭?路5, 鈭?4路6 to 鈭?路5; p=0路0002).

Interpretation

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.

Funding

Merck & Co Inc.