0405 Randomized Controlled Clinical Polysomnography Trial of Suvorexant for Treating Insomnia in Patients with Alzheimer's Disease. (12th April 2019)

• Record Type: Journal Article
• Authors: Herring, W Joseph; Ceesay, Paulette; Snyder, Ellen; Bliwise, Donald; Budd, Kerry; Hutzelmann, Jill; Stevens, Joanne; Michelson, David
• Is Part Of: Sleep. Volume 42(2019)Supplement 1
• Page Start: A164
• Page End: A164
• Publication Date: 2019-04-12
• Subjects: Sleep -- Physiological aspects -- Periodicals; Sleep disorders -- Periodicals; Sommeil -- Aspect physiologique -- Périodiques; Sommeil, Troubles du -- Périodiques; Sleep disorders; Sleep -- Physiological aspects; Sleep -- physiological aspects; Sleep Wake Disorders; Psychophysiology; Electronic journals; Periodicals; 616.8498
• DOI: 10.1093/sleep/zsz067.404
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Introduction: Sleep disturbance and insomnia are common in patients with Alzheimer's disease (AD) but evidence for the efficacy of sleep medications in this population is limited. Suvorexant, a first-in-class orexin receptor antagonist that enables sleep to occur via competitive antagonism of wake-promoting orexins, is approved for treating insomnia in elderly and non-elderly adults. We conducted a clinical trial to evaluate its efficacy and safety for treating insomnia in patients with AD using sleep laboratory polysomnography (PSG) assessments. Methods: This randomized, placebo-controlled trial consisted of a 3-week screening period followed by a double-blind 4-week treatment period (ClinicalTrials.gov: NCT02750306). Patients met diagnostic criteria for both AD and insomnia and had a qualified trial partner/caregiver. Participants were randomized to an initial dose of suvorexant 10mg, that could be increased to 20mg based on clinical response, or matching placebo. Assessments included overnight sleep laboratory PSG visits, a sleep diary completed by the trial partner, an activity/sleep watch worn by the patient, and exploratory measures of cognition and neuropsychiatric behavior. The primary objective was to test the hypothesis that suvorexant would be superior to placebo in improving PSG-derived total sleep time (TST) at Week-4. Results: A total of 285 participants (suvorexant N=142, placebo N=143) were randomized from 35 sites in 8 countries worldwide. Of these, 277 (97%) completed the study (suvorexant N=136, placebo N=141). One patient in each group discontinued study treatment due to an adverse event. Mean (SD) TST at baseline was 278 (77) minutes for suvorexant and 274 (84) minutes for placebo. At Week-4, the model-based least squares mean changes-from-baseline were 73 minutes for suvorexant and 45 minutes for placebo (difference = 28 minutes [95% CI:11, 45], p<0.005). Regarding safety, 22.5% of suvorexant-treated patients and 16.1% of placebo-treated patients experienced ≥1 adverse events. Somnolence was reported in 4.2% of suvorexant-treated patients and 1.4% of placebo-treated patients. Conclusion: Suvorexant was effective and generally well-tolerated for treating insomnia in patients with AD. Support (If Any): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA