In a randomized placebo-controlled phase 3 study (NCT03545191), sleep onset and sleep maintenance were significantly improved by daridorexant (Idorsia Pharmaceuticals, Allschwil, Switzerland) compared with placebo. Sleep onset and maintenance were measured in a sleep lab by polysomnography in adult participants, including people more than age 65, who were given placebo or daridorexant (25 mg or 50 mg).
Daridorexant, a dual orexin receptor antagonist, also significantly improved subjective total sleep time as measured daily with a patient diary at home. Daytime performance improved significantly as well, as measured by participants feeling less physically and mentally tired, less sleepy, and more energetic during the day.
Improvements with daridorexant vs placebo were statistically significant at month 1 and at month 3, indicating sustained benefit.
“Pharmacological treatment for insomnia should not only help patients to fall asleep quickly and to stay asleep but also address the negative impact of poor sleep on daytime functioning,” said Thomas Roth, PhD, director of the Sleep Disorder and Research Center at Henry Ford Hospital. “I believe that the optimal way to achieve this is through blocking the action of orexin and therefore turning down overactive wakefulness seen among insomnia disorder patients. This will allow patients to sleep throughout the night, while avoiding the adverse effects associated with many sleep medications that act through broad sedation of the brain. The excellent results seen in this phase 3 study of 3-month duration suggests that daridorexant can fulfil this significant need for patients with insomnia.”
The study of 930 participants (39.1% > 65 years of age) demonstrated efficacy based on sleep parameters and daytime performance with no residual effect in the morning and no evidence of rebound or withdrawal upon discontinuation of treatment.