Long-term safety and efficacy of vornorexant in Japanese patients with insomnia: A 52-week open-label, randomized trial.

STUDY OBJECTIVES: This study aimed to evaluate the long-term safety and efficacy of vornorexant, a novel dual orexin receptor antagonist, in Japanese patients with insomnia. METHODS: This multicenter, randomized, open-label trial consisted of a 1-week screening period, an initial 26-week treatment period followed by an optional 26-week extension (for a total of up to 52 weeks), and a 1-week single-blind placebo run-out period. Patients received vornorexant 5 mg (VOR5) or vornorexant 10 mg (VOR10) during the treatment period(s). Safety assessments included adverse events, withdrawal symptoms, and rebound insomnia. Efficacy for sleep onset and maintenance was evaluated using patient-reported sleep diaries. Subgroup analyses by age and sex were conducted. RESULTS: A total of 371 patients were randomized; 38 discontinued during the initial period and 8 during the extension. The most common adverse events were nasopharyngitis (10.9% and 8.2%) and somnolence (5.4% and 12.0%) in VOR5 and VOR10, respectively. No withdrawal symptoms and rebound insomnia of clinical concern were detected. Regarding efficacy, mean change from baseline (CFB) in subjective sleep latency were -31.2 and -38.9 min at week 26 and -31.8 and -44.0 min at week 52 for VOR5 and VOR10, respectively. For sleep maintenance, mean CFB in subjective sleep efficiency were 14.07% and 17.63% at week 26 and 15.56% and 20.40% at week 52, respectively. Changes were generally similar across age and sex subgroups; however, psychiatric comorbidity subgroup analyses were underpowered. CONCLUSIONS: Long-term vornorexant treatment was well tolerated, and improvements in sleep onset and sleep maintenance were observed for up to 52 weeks in Japanese patients with insomnia.