The Effects of Daridorexant on Patients With Comorbid Insomnia Disorder and Untreated Mild Obstructive Sleep Apnoea: A Post Hoc Subgroup Analysis of a Phase 3, Randomised Clinical Trial

ABSTRACT Daridorexant, a dual orexin receptor antagonist, is approved for the treatment of insomnia disorder in adults. Approximately 30%–35% of patients with insomnia disorder also have obstructive sleep apnoea (OSA) of any severity. It is unclear whether sleep medications provide safe and effective treatment for insomnia in these patients. This post hoc analysis evaluated the efficacy and safety of daridorexant 25 and 50 mg on objective and self‐reported insomnia variables and self‐reported daytime functioning in patients with untreated mild OSA and comorbid insomnia disorder (COMISA). This analysis included participants with insomnia disorder enrolled in the Phase 3 study assessing either daridorexant 25 or 50 mg with an apnoea/hypopnoea index 5–< 15 events/h (‘mild OSA’). Wake after sleep onset (WASO), latency to persistent sleep (LPS), self‐reported total sleep time (sTST) and the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) were assessed at Months 1 and 3. Safety endpoints were treatment‐emergent adverse events, daytime somnolence and next‐morning residual effects. In participants with mild OSA, daridorexant improved WASO, LPS, sTST and IDSIQ total score over time. The average treatment effect size for all efficacy parameters was numerically greater with daridorexant 50 mg than with daridorexant 25 mg; daridorexant 25 mg was not always greater than placebo. No safety concerns were reported for daridorexant 50 or 25 mg. In participants with comorbid insomnia and untreated mild OSA, daridorexant 50 mg versus placebo improved all sleep parameters over time and was well tolerated. Daridorexant warrants further investigation in COMISA. Trial Registration: ClinicalTrials.gov identifier: NCT03545191