Daridorexant improves sleep outcomes and daytime functioning in insomnia patients: Lancet

USA: In persons with insomnia conditions, daridorexant 25 mg and 50 mg improved sleep outcomes, and daridorexant 50 mg also improved daytime functioning, with a favorable safety profile, says an article published in The Lancet Neurology.

In those with insomnia disorder, daytime functioning is hindered. Dual orexin receptor antagonists, which are now available, have proven beneficial in insomnia problems, although they do not treat all elements of the condition. Therefore Emmanuel Mignot and team conducted this study with the goal to see how safe and effective daridorexant, a new orexin receptor antagonist, was in treating insomnia symptoms both at night and during the day.

For this study, in trial 1, 930 individuals were randomly allocated to receive daridorexant 50 mg (n=310), daridorexant 25 mg (n=310), or placebo (n=310) between June 4, 2018 and February 25, 2020. In trial 2, 924 individuals were randomly allocated to receive daridorexant 25 mg (n=309), daridorexant 10 mg (n=307), or placebo (n=308) between May 29, 2018, and May 14, 2020.

At 156 locations in 17 countries, researchers conducted two multicenter, randomized, double-blind, placebo-controlled phase 3 studies. Adults (aged 18 years) with insomnia problems were randomly allocated to receive daridorexant 50 mg, 25 mg, or placebo (study 1) or daridorexant 25 mg, 10 mg, or placebo (study 2) every evening for three months utilizing interactive response technology. Treatment allocation was kept a secret from participants, investigators, and site staff. Changes in waking time after sleep onset (WASO) and latency to persistent sleep (LPS), as evaluated by polysomnography, during months 1 and 3 were the primary objectives. Changes from baseline in self-reported total sleep time and the sleepiness domain score of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) at months 1 and 3 were used as secondary outcomes. For all pairwise comparisons, the study-specific type I error rate (5%) was controlled. All individuals who were randomly allocated were evaluated for efficacy, and all participants who received at least one dose of medication were evaluated for safety.

At month 1 and month 3, WASO and LPS were considerably lower in the daridorexant 50 mg group compared to the placebo group in research 1. At month 1 and month 3, participants in the daridorexant 25 mg group had significantly lower WASO and LPS than those in the placebo group. Participants in the daridorexant 50 mg group showed substantially better self-reported total sleep time and IDSIQ sleepiness domain scores at month 1 and month 3 when compared to placebo. Participants in the daridorexant 25 mg group had substantially better self-reported total sleep time at month 1 and month 3, but not IDSIQ sleepiness domain scores, as compared to the placebo group.

In trial 2, WASO was considerably lower in the daridorexant 25 mg group compared to the placebo group at month 1 and month 3, but no significant changes in LPS were identified at either month 1 or month 3. Participants in the daridorexant 25 mg group demonstrated substantial improvements in self-reported total sleep time at month 1 and month 3, but not in IDSIQ sleepiness domain scores, as compared to the placebo group. There were no significant differences in WASO, LPS, self-reported total sleep duration, or IDSIQ sleepiness domain scores between the daridorexant 10 mg group and the placebo group. The overall rate of adverse events was similar between treatment groups.

The most prevalent adverse effects in all groups were nasopharyngitis and headache. In study 1, one fatality (cardiac arrest) occurred in the daridorexant 25 mg group that was not attributed to the drug.

Reference:

Mignot, Emmanuel & Mayleben, David & Fietze, Ingo & Leger, Damien & Zammit, Gary & Bassetti, Claudio & Pain, Scott & Kinter, Dalma & Roth, Thomas. (2022). Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. The Lancet Neurology. 21. 125-139. https://doi.org/10.1016/S1474-4422(21)00436-1.