STUDY OBJECTIVES: Suvorexant (MK-4305) is an orexin receptor antagonist being 
developed for the treatment of insomnia. This report describes the effects of 
nighttime administration of suvorexant on polysomnography (PSG) sleep parameters 
in healthy young men.
DESIGN: Randomized, double-blind, placebo-controlled, 4-period crossover PSG 
study, followed by an additional 5(th) period to assess pharmacokinetics.
SETTING: Sleep laboratory.
PARTICIPANTS: Healthy young men between 18 and 45 years of age (22 enrolled, 19 
completed).
INTERVENTIONS: Periods 1-4: suvorexant (10 mg, 50 mg, or 100 mg) or placebo 1 h 
before nighttime PSG recording. Period 5: suvorexant 10 mg, 50 mg, or 100 mg.
MEASUREMENTS AND RESULTS: In Periods 1-4, overnight sleep parameters were 
recorded by PSG and next-morning residual effects were assessed by psychomotor 
performance tests and subjective assessments. Statistically significant 
sleep-promoting effects were observed with all doses of suvorexant compared to 
placebo. Suvorexant 50 mg and 100 mg significantly decreased latency to 
persistent sleep and wake after sleep onset time, and increased sleep 
efficiency. Suvorexant 10 mg significantly decreased wake after sleep onset 
time. There were no statistically significant effects of suvorexant on EEG 
frequency bands including delta (slow wave) activity based on power spectral 
analysis. Suvorexant was well tolerated. There was no evidence of next-day 
residual effects for suvorexant 10 mg. Suvorexant 50 mg statistically 
significantly reduced subjective alertness, and suvorexant 100 mg significantly 
increased reaction time and reduced subjective alertness. There were no 
statistically significant effects of any suvorexant dose on digit symbol 
substitution test performance. In Period 5, plasma samples of suvorexant were 
collected for pharmacokinetic evaluation. The median T(max) was 3 hours and 
apparent terminal t(½) was 9-13 hours.
CONCLUSIONS: In healthy young men without sleep disorders, suvorexant promoted 
sleep with some evidence of residual effects at the highest doses.