Insomnia: Phase 3 Daridorexant Trial Yields Positive Results
The dual orexin receptor antagonist daridorexant was found to be safe and effective for the treatment of insomnia in adult and elderly patients, according to new findings presented at the SLEEP 2020 Virtual Annual Meeting.1
Thomas Roth, PhD, and colleagues arrived at their conclusion after performing a phase 3, multi-center, double-blind, randomized, placebo-controlled, polysomnography study of daridorexant among 930 patients with insomnia. Participants were randomly assigned to 25 mg or 50 mg daridorexant or placebo. Treatments were administered each night for 3 months following a week of placebo at baseline and a subsequent week of placebo run-out.
The primary endpoints of the trial were defined as change from baseline in several polysomnography sleep parameters, including wake time after sleep onset (WASO) and latency to persistent sleep (LPS), which were measured at months 1 and 3. Secondary endpoints were defined as change from baseline in subjective total sleep time (sTST) and daytime functioning, which were measured via the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) sleepiness score. The score was used to assess sleepiness, energy, and mental and physical tiredness.
The results of the trial demonstrated an improvement in WASO from baseline of -18.40 minutes for 25 mg daridorexant, -28.98 minutes for 50 mg daridorexant, and -6.20 minutes for placebo at 1 month. At 3 months, corresponding improvements were -22.97 minutes, -29.41 minutes, and -11.11 minutes, respectively.
Improvements in LPS from baseline were -28.17 for 25 mg daridorexant, -31.20 for 50 mg daridorexant, and -19.85 for placebo at 1 month, with values of -30.73, -34.80, and -23.13, respectively, at 3 months.
The authors observed increased in sTST from baseline of 34.18 minutes for 25 mg daridorexant, 43.62 minutes for 50 mg daridorexant, and 21.56 minutes for placebo at 1 month. Corresponding values at 3 months were 47.85, 57.67, and 37.90, respectively. Improvements in daytime functioning were -2.77 for 25 mg daridorexant, -3.77 for 50 mg daridorexant, and -2.02 for placebo at 1 month, with values of -4.78, -5.70, and -3.79, respectively, at 3 months.
“As hypothesized, the optimized profile of daridorexant not only translated in this study into a dose-dependent improvement on objective and subjective sleep parameters, but also into improved daytime functioning, all of which was sustained over time,” said Dr Roth, who is director of the Sleep Disorder and Research Center at Henry Ford Hospital, in a press release.2 “Very importantly, safety was comparable with daridorexant 25 mg and 50 mg, with no dose-limiting safety findings, no observed next-morning sleepiness compared to placebo, no signals suggestive of rebound insomnia compared to baseline sleep parameters, and no withdrawal effects,” Dr Roth added.2
The most common adverse effects associated with daridorexant included nasopharyngitis and headache, which occurred similarly between treatment groups. Somnolence occurred among 6 participants on placebo, 11 participants on 25 mg daridorexant, and 5 participants on 50 mg daridorexant.
“With these results daridorexant addresses important needs of patients with insomnia,” Dr Roth said.2
- Roth T, Zammit G, Mignot E, et al. LBA4: phase 3, multi-center, double-blind, randomized, placebo-controlled, polysomnography study to assess efficacy and safety of daridorexant in adult and elderly insomnia patients. https://www.sleepmeeting.org/wp-content/uploads/2020/08/Virtual-SLEEP-Guide_NonAttendee_8.27.20_compressed.pdf
- Daridorexant phase 3 results in insomnia presented at SLEEP 2020. News release. Idorsia Pharmaceuticals LTD. August 28, 2020. https://www.idorsia.com/media/news-details?newsId=2359821