A randomised crossover trial of daridorexant for the treatment of chronic insomnia and nocturia

Summary This double‐blind, placebo‐controlled, two‐way crossover trial evaluated the efficacy and safety of daridorexant in patients with chronic insomnia and comorbid nocturia. In total, 60 patients aged ≥55 years with insomnia complaints for ≥3 months, Insomnia Severity Index (ISI) ≥13 and ≥3 voids/night for ≥1 month were randomised (1:1) to daridorexant 50 mg/placebo for 4 weeks followed by crossover after a 14–21‐day washout period. The primary endpoint was change from baseline to Week (W) 4 in self‐reported total sleep time (sTST). Other endpoints included change in ISI score, sleep depth and quality (visual analogue scale scores), nocturnal voids (mean number, time to first) and daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire score [IDSIQ]). At W4, daridorexant significantly increased sTST versus placebo (least‐squares mean difference [LSMD] 20.9 min, 95% confidence interval [CI] 8.0–33.7; p = 0.002); significant improvements were also seen at W1–3. Compared with placebo, daridorexant significantly decreased ( p < 0.001) ISI at both timepoints, W2 (LSMD −3.7, 95% CI −5.1 to −2.3) and W4 (LSMD −3.3, 95% CI −4.7 to −1.8) and significantly improved ( p < 0.05) sleep depth (W1, 2, 3, 4), sleep quality (W1, 2, 3) and IDSIQ total score (W1, 3). Daridorexant versus placebo reduced the number of voids (LSMD [95% CI]: W1–0.6 [−0.9 to −0.3], p < 0.001; W4–0.3 [−0.7 to +0.1], p = 0.090) and increased median time to first void (difference to placebo, W1: +31 min, p = 0.0027; W4: +23 min, p = 0.2026). No adverse events of special interest (falls/urinary incontinence) were reported during daridorexant treatment. In conclusion, in patients with chronic insomnia and nocturia, daridorexant improves both conditions with a favourable safety profile.