C. Lines’s research while affiliated with Merck & Co. and other places

Introduction Suvorexant, an orexin receptor antagonist that enables sleep to occur via competitive antagonism of wake-promoting orexins, improved total sleep time (TST) in a sleep laboratory polysomnography (PSG) study of patients with AD and insomnia. Here we report on the effects of suvorexant on sleep architecture in the study. Methods This was a randomized, double-blind, 4-week trial (ClinicalTrials.gov NCT02750306). Participants who met diagnostic criteria for both probable AD dementia (of mild to moderate severity) and insomnia were randomized to suvorexant 10mg (could be increased to 20mg based on clinical response) or matching placebo. Overnight sleep laboratory PSG was performed on 3 nights: screening, baseline, and Night-29 (last night of dosing). Suvorexant differences from placebo in changes-from-baseline at Night-29 for sleep architecture were analyzed as exploratory endpoints. Results A total of 274 participants were included in the analysis (suvorexant N=135, placebo N=139). At Night-29, suvorexant improved TST by 28 minutes versus placebo (p=0.001). There were no significant differences between suvorexant and placebo in the % of TST spent in REM (1.3%, 95% CI: -0.5, 3.0), N1 (0.6%, 95% CI: -1.2, 2.5), N2 (-1.0%, 95% CI: -3.2, 1.2), or N3 (-0.6%, 95% CI: -1.8, 0.6). There was no significant difference between suvorexant and placebo in latency to REM (-5.4 minutes, 95% CI: -23.4, 12.7). Conclusion Suvorexant improves TST without altering the underlying sleep architecture in AD patients with insomnia. Support Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Introduction Suvorexant, an orexin receptor antagonist, improved total sleep time (TST) in a sleep laboratory polysomnography (PSG) study of patients with Alzheimer’s disease (AD) and insomnia. The study included a pilot evaluation of an actigraphy watch for continuously recording patient’s sleep and daytime activity. We report on the utility of the watch for assessing sleep in relation to gold-standard PSG. Methods This was a randomized, double-blind, 4-week trial (ClinicalTrials.gov NCT02750306). Participants who met diagnostic criteria for both probable AD dementia and insomnia were randomized to suvorexant 10-20mg or placebo. Overnight sleep laboratory PSG was performed on 3 nights: screening, baseline, and Night-29 (last dose). An actigraphy watch (Garmin vívosmart® HR) was worn continuously by the patient. Separate analyses were performed for PSG and watch. We compared treatment effects on change-from-baseline in PSG-TST at Night-29 and WATCH-TST at Week-4 (average TST per night over Week-4). We also analyzed Night-29 data only with watch data restricted to the PSG recording time. Results A total of 274 participants were included in the Night-29 PSG analysis (suvorexant=135, placebo=139) and 223 in the Week-4 watch analysis (suvorexant=113, placebo=110). Suvorexant improved Night-29 PSG-TST by 28 minutes versus placebo (p=0.001) and Week-4 WATCH-TST by 17 minutes versus placebo (p=0.144). In the subgroup who had usable data for both assessments at Night-29 (suvorexant=57, placebo=50), the watch overestimated TST compared to PSG (e.g. placebo baseline scores = 412 minutes for WATCH-TST and 265 minutes for PSG-TST) and underestimated change-from-baseline treatment effects: the suvorexant versus placebo difference was 35 minutes for PSG-TST (p=0.057) and 20 minutes for WATCH-TST (p=0.405). Conclusion The watch was less sensitive than PSG for evaluating treatment effects on TST. However, results obtained with the watch were directionally similar to PSG in indicating a benefit of suvorexant versus placebo for improving TST in AD patients with insomnia. Support Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA