Purpose: Fazamorexant is a dual orexin receptor antagonist being developed for the treatment of insomnia. This study aims to determine the dose-exposure-response relationship of single-dose fazamorexant versus zolpidem in young adult and elderly healthy Chinese volunteers. Methods: This was a single-center, randomized, double-blind, double-dummy, placebo- and active-controlled, 4-period crossover study. The dose of fazamorexant was 40mg/80mg in young adults and 20mg/40mg in the elderly, while zolpidem was administered at the clinically recommended dose, 10mg. Pharmacokinetic and pharmacodynamic measurements were scheduled during each period. Safety was assessed throughout the study. Results: There was no significant pharmacokinetic difference between young adults and the elderly with fazamorexant. In general, high-dose fazamorexant caused similar or less impairment versus zolpidem in eye movements, choice-reaction-time performance, body sway, and memory tests in young and elderly cohorts. The effects of low-dose fazamorexant on these psychomotor and cognitive measurements were significantly smaller than those of high-dose fazamorexant and zolpidem in both age cohorts. Despite of similarity in exposure, fazamorexant demonstrated larger effects on the pharmacodynamic measurements in the elderly than in young adults, suggesting an age-related increase of pharmacological sensitivity. Conclusion: Fazamorexant induced less balance, judgement and memory impairment compared to the comprehensive suppression of zolpidem on the neurological system. Such favorable spectrum makes fazamorexant a potentially safer drug for insomnia. No age-related pharmacokinetic difference was identified with fazamorexant. Key words: Fazamorexant, Zolpidem, pharmacokinetics, pharmacodynamics, insomnia.