Efficacy and safety of daridorexant in Chinese patients with insomnia disorder: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial

STUDY OBJECTIVES: To evaluate the efficacy and safety of daridorexant in Chinese patients with insomnia disorder. METHODS: This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase III clinical trial in China. Adults aged 18-75 years meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for insomnia disorder, with a baseline Insomnia Severity Index (ISI) more than equal to 15, were randomly assigned in a 1:1 ratio to receive daridorexant 50 mg or placebo once every evening for 1 month. The primary endpoint was the change from baseline to month 1 in wake time after sleep onset (WASO) assessed by polysomnography (PSG). The secondary endpoints included the change from baseline to month 1 in self-reported total sleep time (sTST) and in latency to persistent sleep (LPS). In addition to the standardized collection of adverse events (AEs), safety data specific to insomnia treatment were assessed as follows: withdrawal symptoms, rebound insomnia, and next-day residual effects. RESULTS: Two hundred and six participants were enrolled and evenly randomized to each group. Compared with the placebo group, the daridorexant group showed a significant reduction in WASO (-15.4 min, p = .0009), a significant increase in sTST (16.8 min, p = .021) and a significant reduction in LPS (geometric mean ratio to placebo 0.7, p = .001) from baseline to month 1. The proportion of participants reporting AEs during double-blind treatment was generally comparable between two groups (21.6 vs. 18.4 percent), with no notable safety signals observed. No withdrawal symptoms, rebound insomnia, and next-day residual effects were observed. CONCLUSIONS: Daridorexant 50 mg significantly improved both objective and self-reported sleep outcomes in Chinese patients with insomnia disorder, with a favorable safety profile. CLINICAL TRIAL: A Study of Daridorexant in Chinese Patients With Insomnia Disorder, https://clinicaltrials.gov/study/NCT06010693, with the number NCT06010693. Statement of Significance Daridorexant has been evaluated and approved for the treatment of insomnia in many countries worldwide, but there is no data of daridorexant in Chinese populations. This study is the first randomized controlled phase III study of daridorexant in Chinese. It verified the efficacy and safety of daridorexant in Chinese people for the first time and fully explained the characteristics of daridorexant in Chinese patients with insomnia. This study provides a basis for the approval of daridorexant for clinical use in China, as well as reference data for clinicians to use the drug in the future.