Efficacy and safety of vornorexant in Japanese patients with insomnia: a randomized, placebo-controlled phase 3 pivotal study.

Study objectives: A placebo-controlled phase 3 study was conducted to evaluate the efficacy and safety of vornorexant, a novel dual orexin receptor antagonist, in Japanese patients with insomnia.

Methods: Following a 2-week placebo run-in period, 596 patients with insomnia were randomized to receive 5 mg of vornorexant (VOR5), 10 mg of vornorexant (VOR10), or placebo for 2 weeks in a 1:1:1 ratio in double-blind manner, followed by a 1-week placebo run-out period. The primary and key secondary efficacy endpoints were subjective sleep latency and subjective sleep efficiency, respectively, assessed by sleep diary.

Results: Subjective sleep latency was significantly improved at week 2 in both groups compared to placebo (differences of the least-squares mean [LSM] changes from baseline in VOR5, -10.6 min [95% confidence interval - 14.2, -7.0] p<.001, and VOR10, -10.1 min [-13.8, -6.5] p<.001). Subjective sleep efficiency was also significantly improved at 2 weeks in both groups compared to placebo (LSM changes from baseline in VOR5, 3.41% [1.87, 4.96] p<.001, and VOR10, 2.94% [1.40, 4.48] p<.001). The most common adverse event was somnolence (VOR5: 3.1%, VOR10: 3.6%, placebo: 1.5%). No adverse events of cataplexy, fall, muscular weakness, sleep paralysis, hypnagogic or hypnopompic hallucination, or excessive daytime sleepiness were reported. No withdrawal symptoms or rebound insomnia were observed in the placebo run-out period.

Conclusion: Treatment with 5 and 10 mg of vornorexant significantly improved sleep onset latency and sleep efficiency compared with placebo without relevant safety concerns.