TY - JOUR
T1 - Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation
T2 - A phase 3 randomised, double-blind, placebo-controlled trial
AU - Michelson, David
AU - Snyder, Ellen
AU - Paradis, Erin
AU - Chengan-Liu, Mary
AU - Snavely, Duane B.
AU - Hutzelmann, Jill
AU - Walsh, James K.
AU - Krystal, Andrew D.
AU - Benca, Ruth M.
AU - Cohn, Martin
AU - Lines, Christopher
AU - Roth, Thomas
AU - Herring, W. Joseph
PY - 2014
Y1 - 2014
N2 - 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 ClinicalTrials.gov, number NCT01021813. 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 (38·7 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). 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.
AB - 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 ClinicalTrials.gov, number NCT01021813. 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 (38·7 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). 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.
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U2 - 10.1016/S1474-4422(14)70053-5
DO - 10.1016/S1474-4422(14)70053-5
M3 - Article
C2 - 24680372
AN - SCOPUS:84898546938
SN - 1474-4422
VL - 13
SP - 461
EP - 471
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 5
ER -