Crossover Trial Highlights Therapeutic Benefit of Daridorexant in Chronic Insomnia and Comorbid Nocturia

Katharina Lederer, PhD

Daridorexant (Quviviq; Idorsia), an FDA-approved medication for insomnia, was recently shown to improve subjective sleep and nocturia symptoms while decreasing daytime impairment in patients with chronic insomnia and nocturia. Overall, data from this placebo-controlled, crossover trial showcased the therapeutic effectiveness and safety of this medication in patients with these overlapping conditions.¹

Published in the Journal of Sleep Research, the trial featured 60 patients with insomnia and nocturia who were randomly assigned to 50 mg doses of either daridorexant (n = 30) or placebo (n = 30) for a 4-week period, followed by a crossover. Coming into the study, patients were experiencing insomnia complaints for at least 3 months, had Insomnia Severity Index (ISI) scores greater than 13, and had at least 3 voids/night for at least 1 month before entering.

Lead author Katharina Lederer, PhD, Advanced Sleep Research GmbH, Berlin, Germany, and colleagues used change in self-reported total sleep time (sTST) at week 4 as the primary end point. At the conclusion of the 4-week trial, investigators observed significant increase in mean sTST in daridorexant-treated patients (+56.6 min; 95% CI, 46.0-67.2 min) relative to placebo (+35.7; 95% CI, 25.0-46.4 min). Overall, there was a least square mean difference of 20.9 min (95% CI, 8.0-33.7; P = .002) between daridorexant and placebo, with significant increases observed within the first 3 weeks of treatment.

After 4 weeks of treatment, daridorexant-treated patients experienced greater decreases in the number of voids per night, a measure of nocturia, relative to placebo (daridorexant: LS mean, –1.6 [95% CI, –2.0 to –1.3) vs placebo: –1.3 [95% CI, –1.6 to –1.0). At week 1 of treatment, 47% of patients on daridorexant reported less than 2 voids/night compared with 19% on placebo. This increased to 53% and 32%, respectively, after 4 weeks of treatment. In terms of timing to first void, the difference between daridorexant and placebo was +31 min (P = .0027) and +23 min (P = .2026) at week 1 and 4, respectively, favoring daridorexant.

Daridorexant, a dual orexin receptor antagonist, was approved in early 2022 following a clinical program that included 1854 adults across 160 clinical trial sites. In the latest data, the medication was shown to be safe and well tolerated, with no serious adverse events observed, nor any AEs leading to study drug discontinuation or death. Relevant treatment-emergent AEs for daridorexant included somnolence, fatigue, and hangover effect.

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Lederer et al noted that, "Strengths of the trial include the placebo-controlled, crossover design, with patients as their own matched control, the inclusion of both male and female patients and 30% Black/African American patients (which represents more than double the proportion of the Black/African American population in the United States and the patient selection based on criteria that identified patients with moderate/severe chronic insomnia and clinically relevant nocturia irrespective of cause."

Daridorexant demonstrated significant improvements over placebo in the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) total scores, with greater reductions observed at Week 1 (P = 0.021) and Week 3 (P = 0.043). At Week 1, the mean reduction in IDSIQ score on daridorexant was 16.8, surpassing the clinically meaningful threshold of 17, and maintained improvements at later timepoints. In contrast, the placebo group had smaller reductions, remaining below 16 units at all timepoints. Similar patterns were observed for the IDSIQ domain scores. Additionally, VAS scores for ability to function and daytime alertness improved more with daridorexant, with statistical significance reached at Week 3 for both endpoints (P < 0.05).

Patient satisfaction was also high with daridorexant, as treated patients had mean satisfaction scores of 7.0 (95% CI, 6.3-7.6). For comparison, those on placebo had scores of 5.3 (95% CI, 4.3-6.2), representing a least square mean difference of 1.7 (95% CI, 0.7-2.7; P = .001). At the conclusion of the study, more patients expressed a preference for daridorexant than placebo (74% vs 26%; OR, 2.6; 95% CI, 1.59-5.16; P = .0004).

REFERENCE
1. Lederer K, Benes H, Fine A, et al. A randomised crossover trial of daridorexant for the treatment of chronic insomnia and nocturia. Journal of Sleep Research. Published online March 13, 2025. doi:10.1111/jsr.70002