A phase 3, randomized, placebo-controlled, double-blind, multicentre trial showed that a novel dual orexin receptor antagonist daridorexant (50 mg) led to improvements in daytime functioning while daridorexant (25 mg and 50 mg) led to significant improvements in sleep outcomes in adults suffering from insomnia.

Investigators undertook this study to explore safety and efficacy of daridorexant on daytime and night-time symptoms of insomnia. The study recruited subjects (aged ≥18 years) suffering from insomnia disorder. With the aid of interactive response technology, participants were randomized to get daridorexant 50 mg (n=310), 25 mg (n=310), or placebo (n=310, study 1) or daridorexant 25 mg (n=309), 10 mg (n=307), or placebo ((n=308, study 2) every evening for about 3 months.

Alteration from baseline in self-reported overall sleep time and the sleepiness domain score of Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) at first and third months were the secondary outcomes ascertained while alteration from the baseline in latency to persistent sleep (LPS) and wake time after sleep onset (WASO) at first and third months were the major outcomes ascertained.

For all the pairwise comparisons, the study-wise type I error rate (5%) was checked. Efficacy was examined in all the randomly allocated subjects, and safety was assessed in all the subjects who received at least 1 dose of therapy.

In study 1, LPS and WASO considerably dropped in subjects in the 50 mg daridorexant arm when compared to subjects in the placebo arm at month 1. LPS and WASO substantially decreased in subjects in the daridorexant 25 mg arm when compared to the placebo arm at month 1 and month 3. In comparison with placebo, subjects in daridorexant 50 mg arm illustrated considerably better self-reported overall sleep time and IDSIQ scores at first and third months.

In comparison with the placebo arm, subjects in the daridorexant 25 mg arm demonstrated considerably better self-reported total sleep time, but not IDSIQ scores at first and third months. In study 2, WASO considerably decreased in subjects in the 25 mg daridorexant arm in comparison with subjects in the placebo arm at month 1 and month 3. However, no profound differences in LPS were noted at month 1 or month 3.

In comparison with placebo arm, subjects in daridorexant 25 mg arm illustrated considerable enhancement in the self-reported total sleep time, but not in the IDSIQ sleepiness domain scores at first and third months. At month 1 and at month 3, no profound differences were noted among subjects in the 10 mg daridorexant arm for WASO, LPS, self-reported total sleep time, nor IDSIQ sleepiness domain scores when compared to the placebo arm.

The overall occurrence of side effects was similar between the therapeutic groups. In all the groups, headache and nasopharyngitis were mostly reported. In study 1, one death (cardiac arrest) took place in the daridorexant 25 mg arm, that was not associated with therapy. Thus, daridorexant is effective and safe for the management of insomnia.