Effects of suvorexant, an orexin receptor antagonist, on sleep parameters as measured by polysomnography in healthy men.
OBJECTIVE
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.


METHODS
Randomized, double-blind, placebo-controlled, 4-period crossover PSG study, followed by an additional 5(th) period to assess pharmacokinetics.


METHODS
Sleep laboratory.


METHODS
Healthy young men between 18 and 45 years of age (22 enrolled, 19 completed).


METHODS
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.


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.
Merck Sharp - Dohme Corp., Whitehouse Station, NJ, USA.
Hong
H
Sun
William P
WP
Kennedy
Darren
D
Wilbraham
Nicole
N
Lewis
Nicole
N
Calder
Xiaodong
X
Li
Junshui
J
Ma
Ka Lai
KL
Yee
Susan
S
Ermlich
Eric
E
Mangin
Christopher
C
Lines
Laura
L
Rosen
Jeffrey
J
Chodakewitz
Gail M
GM
Murphy
D000293:Adolescent; D000328:Adult; D001381:Azepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D064446:Orexin Receptors; D017286:Polysomnography; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
D001381:Azepines; D006993:Hypnotics and Sedatives; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014230:Triazoles; C551624:suvorexant