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Randomized Controlled Trial
. 2025 Dec;34(6):e70002.
doi: 10.1111/jsr.70002. Epub 2025 Mar 13.

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

Katharina Lederer  1 , Heike Benes  2 , Alan Fine  3 , Sylvia Shoffner  4 , Sandro Bacchelli  5 , David Castro Diaz  6 , Jose Emilio Batista  7 , Racheal Rowles  8 , Tobias Di Marco  8 , Michael Meinel  8
Affiliations
Randomized Controlled Trial

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

Katharina Lederer et al. J Sleep Res. 2025 Dec.

Abstract

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.

Keywords: daridorexant; dual orexin receptor antagonist; insomnia; nocturia; total sleep time; voids.

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Conflict of interest statement

Heike Benes has received speaker fees from Idorsia Pharmaceuticals and participated in advisory boards from Idorsia Pharmaceuticals and Takeda. Jose Emilio Batista has received CME grants from Lacer Italfarmaco, Astellas Europe, Hollister and Coloplast. Michael Meinel, Racheal Rowles and Tobias Di Marco were all employees of Idorsia Pharmaceuticals Ltd at the time of the study. Alan Fine, David Castro Diaz, Katharina Lederer, Sandro Bacchelli, and Sylvia Shoffner have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Patient disposition.
FIGURE 2
FIGURE 2
Mean changes from baseline over time in efficacy endpoints. Mean change from baseline in (a) subjective total sleep time (sTST, min), (b) Insomnia Severity Index (ISI), (c) Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) total score, (d) number of voids/night. sTST was collected every day in the morning and weekly averages were calculated. The ISI (scale 0–28) was collected after Week 2 and 4 of each treatment period. The IDSIQ (scale from 0 to 140) was collected every day in the evening and weekly averages were calculated. Number of voids was collected for 3 consecutive days at the beginning (Week 1) and the end of each treatment period (Week 4). Error bars show the standard error of the mean. Two‐sided p values shown are versus placebo.
FIGURE 3
FIGURE 3
Mean change from baseline over time on subjective assessment of sleep and daytime symptoms assessed by visual analogue scale (VAS). Weekly mean change from baseline in the 100‐mm VAS (a) quality of sleep, (b) depth of sleep, (c) ability to function and (d) daytime alertness. Higher VAS scores indicate better scores. Error bars show the standard error of the mean. Two‐sided p values shown are versus placebo.
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