Effects of the orexin receptor antagonist suvorexant on respiration during sleep in healthy subjects

Suvorexant is an orexin receptor antagonist for treating insomnia. The maximum approved dose in the United States and Japan is 20mg. We evaluated suvorexant effects on respiration during sleep in a randomized, double-blind, 3-period crossover study of healthy adult men (n=8) and women (n=4) 50 years old who received single-dose suvorexant 40mg, 150mg, and placebo. Respiration during sleep was measured by oxygen saturation (SpO(2), primary end point) and the Apnea Hypopnea Index (AHI). The study was powered to detect a reduction greater than 5% in SpO(2). There was no effect of suvorexant on mean SpO(2) during sleep. The mean (90%CI) treatment differences versus placebo were -0.3 (-1.2-0.6) for 40mg and 0.0 (-0.9-0.9) for 150mg. There were no dose-related trends in individual SpO(2) values. Mean SpO(2) was >96% for all treatments during total sleep time and during both non-REM and REM sleep. There was no effect of either suvorexant dose on AHI. The mean (90%CI) treatment differences versus placebo were 0.8 (-0.7-2.3) for 40mg and -0.2 (-1.7-1.3) for 150mg. Suvorexant was generally well tolerated; there were no serious adverse experiences or discontinuations. These data from healthy subjects suggest that suvorexant lacks clinically important respiratory effects during sleep at doses greater than the maximum recommended dose for treating insomnia.