BACKGROUND: Suvorexant is an orexin receptor antagonist for treatment of insomnia. We report results from two pivotal phase 3 trials. METHODS: Two randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in nonelderly (18-64 years) and elderly (≥65 years) patients with insomnia. Suvorexant doses of 40/30 mg (nonelderly/elderly) and 20/15 mg (nonelderly/elderly) were evaluated. The primary focus was 40/30 mg, with fewer patients randomized to 20/15 mg. There was an optional 3-month double-blind extension in trial 1. Each trial included a 1-week, randomized, double-blind run-out after double-blind treatment to assess withdrawal/rebound. Efficacy was assessed at week 1, month 1, and month 3 by patient-reported subjective total sleep time and time to sleep onset and in a subset of patients at night 1, month 1, and month 3 by polysomnography end points of wakefulness after persistent sleep onset and latency to onset of persistent sleep (LPS). One thousand twenty-one patients were randomized in trial 1 and 1019 patients in trial 2. RESULTS:Suvorexant 40/30 mg was superior to placebo on all subjective and polysomnography end points at night 1/week 1, month 1, and month 3 in both trials, except for LPS at month 3 in trial 2. Suvorexant 20/15 mg was superior to placebo on subjective total sleep time and wakefulness after persistent sleep onset at night 1/week 1, month 1, and month 3 in both trials and at most individual time points for subjective time to sleep onset and LPS in each trial. Both doses of suvorexant were generally well tolerated, with <5% of patients discontinuing due to adverse events over 3 months. The results did not suggest the emergence of marked rebound or withdrawal signs or symptoms when suvorexant was discontinued. CONCLUSIONS: Suvorexant improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated.
RCT Entities:
BACKGROUND:Suvorexant is an orexin receptor antagonist for treatment of insomnia. We report results from two pivotal phase 3 trials. METHODS: Two randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in nonelderly (18-64 years) and elderly (≥65 years) patients with insomnia. Suvorexant doses of 40/30 mg (nonelderly/elderly) and 20/15 mg (nonelderly/elderly) were evaluated. The primary focus was 40/30 mg, with fewer patients randomized to 20/15 mg. There was an optional 3-month double-blind extension in trial 1. Each trial included a 1-week, randomized, double-blind run-out after double-blind treatment to assess withdrawal/rebound. Efficacy was assessed at week 1, month 1, and month 3 by patient-reported subjective total sleep time and time to sleep onset and in a subset of patients at night 1, month 1, and month 3 by polysomnography end points of wakefulness after persistent sleep onset and latency to onset of persistent sleep (LPS). One thousand twenty-one patients were randomized in trial 1 and 1019 patients in trial 2. RESULTS:Suvorexant 40/30 mg was superior to placebo on all subjective and polysomnography end points at night 1/week 1, month 1, and month 3 in both trials, except for LPS at month 3 in trial 2. Suvorexant 20/15 mg was superior to placebo on subjective total sleep time and wakefulness after persistent sleep onset at night 1/week 1, month 1, and month 3 in both trials and at most individual time points for subjective time to sleep onset and LPS in each trial. Both doses of suvorexant were generally well tolerated, with <5% of patients discontinuing due to adverse events over 3 months. The results did not suggest the emergence of marked rebound or withdrawal signs or symptoms when suvorexant was discontinued. CONCLUSIONS:Suvorexant improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated.
Authors: W Joseph Herring; Kathleen M Connor; Ellen Snyder; Duane B Snavely; Ying Zhang; Jill Hutzelmann; Deborah Matzura-Wolfe; Ruth M Benca; Andrew D Krystal; James K Walsh; Christopher Lines; Thomas Roth; David Michelson Journal: J Clin Sleep Med Date: 2016-09-15 Impact factor: 4.062
Authors: W Joseph Herring; Kathryn M Connor; Ellen Snyder; Duane B Snavely; Ying Zhang; Jill Hutzelmann; Deborah Matzura-Wolfe; Ruth M Benca; Andrew D Krystal; James K Walsh; Christopher Lines; Thomas Roth; David Michelson Journal: Psychopharmacology (Berl) Date: 2017-03-07 Impact factor: 4.530
Authors: Jessica X Chong; Kati J Buckingham; Shalini N Jhangiani; Corinne Boehm; Nara Sobreira; Joshua D Smith; Tanya M Harrell; Margaret J McMillin; Wojciech Wiszniewski; Tomasz Gambin; Zeynep H Coban Akdemir; Kimberly Doheny; Alan F Scott; Dimitri Avramopoulos; Aravinda Chakravarti; Julie Hoover-Fong; Debra Mathews; P Dane Witmer; Hua Ling; Kurt Hetrick; Lee Watkins; Karynne E Patterson; Frederic Reinier; Elizabeth Blue; Donna Muzny; Martin Kircher; Kaya Bilguvar; Francesc López-Giráldez; V Reid Sutton; Holly K Tabor; Suzanne M Leal; Murat Gunel; Shrikant Mane; Richard A Gibbs; Eric Boerwinkle; Ada Hamosh; Jay Shendure; James R Lupski; Richard P Lifton; David Valle; Deborah A Nickerson; Michael J Bamshad Journal: Am J Hum Genet Date: 2015-07-09 Impact factor: 11.025
Authors: Annemiek Vermeeren; Hong Sun; Eric F P M Vuurman; Stefan Jongen; Cees J Van Leeuwen; Anita C M Van Oers; John Palcza; Xiadong Li; Tine Laethem; Ingeborg Heirman; An Bautmans; Matthew D Troyer; Rebecca Wrishko; Jacqueline McCrea Journal: Sleep Date: 2015-11-01 Impact factor: 5.849