Daridorexant 25 mg and 50 mg may improve sleep outcomes, and daridorexant 50 mg also may improve daytime functioning among patients with insomnia disorder, according to a study published in the Lancet Neurology.
Patients with insomnia disorder experience daytime functional impairment. Daridorexant, the novel dual orexin receptor antagonist, was specifically designed as a medication for insomnia to help improve sleep onset and sleep maintenance without residual effects that would affect daytime functioning, the researchers explained.
Previous phase 2 trials have shown sleep variables improved among adults and older adults, aged 65-85 years, with insomnia, who took daridorexant, without residual sleepiness the next day.
The objective of the current study was to assess the safety and efficacy of this drug in patients with insomnia via 2 placebo-controlled phase 3 trials.
Study 1 participants were randomly assigned (1:1:1) to receive daridorexant 25 mg, daridorexant 50 mg, or placebo. Study 2 participants were randomly assigned (1:1:1) to receive daridorexant 10 mg, daridorexant 25 mg, or placebo. Randomization was stratified by age (<65 years and ≥65 years).
The change from baseline in wake time after sleep onset (WASO) and latency to persistent sleep (LPS) at months 1 and 3, measured with polysomnography in a sleep laboratory, were the primary endpoints.
A total of 3326 participants were screened for inclusion in study 1, of whom 930 received either daridorexant 25 mg (n=310), daridorexant 50 mg (n=310), or placebo (n=310) from June 4, 2018 to February 25, 2020. In addition, 3683 participants were screened for inclusion in study 2, of whom 924 received either daridorexant 10 mg (n=307), daridorexant 25 mg (n=309), or placebo (n=308) from May 29, 2018 to May 14, 2020.
In study 1, 624 participants (67%) were female, and in study 2, 638 participants (69%) were female; 364 (39%) participants in study 1 and 363 (39%) participants in study 2 were aged ≥65 years. Overall, 1650 participants (89%) were White, and 148 (8%) were Black or African American.
In study 1, WASO was significantly decreased from baseline in the daridorexant 50-mg group vs the placebo group at month 1 (least squares mean [LSM] difference –22.8 min [95% CI, −28.0 to −17.6], P <.0001) and month 3 (−18.3 min [−23.9 to −12.7], P <.0001). LPS was significantly decreased vs the placebo group at month 1 (LSM difference −11.4 min) and month 3 (−11.7 min). Self-reported total sleep time was significantly increased in the daridorexant 50-mg group at month 1 (LSM difference 22.1 min) and month 3 (19.8 min) vs the placebo group.
WASO was also significantly decreased in the daridorexant 25-mg group vs the placebo group at 1 month (LSM difference −12.2 min [95% CI, −17.4 to −7.0], P < .0001) and month 3 (−11.9 min [−17.5 to −6.2], P <.0001). LPS was significantly decreased vs the placebo group at month 1 (−8.3 min [−13.0 to −3.6], P =.0005) and month 3 (−7.6 min [−12.3 to −2.9], P =.0015). Self-reported total sleep time was significantly increased in the daridorexant 25-mg group at month 1 (LSM difference 12.6 min) and month 3 (9.9 min) vs the placebo group.
In study 2, WASO was significantly decreased in the daridorexant 25-mg group vs the placebo group at month 1 (LSM difference −11.6 min [95% CI, −17.6 to −5.6], P =.0001) and month 3 (−10.3 min [−17.0 to −3.5], P =.0028). Self-reported total sleep time was significantly increased vs the placebo group at month 1 (LSM difference 16.1 min) and month 3 (19.1 min). No significant differences in LPS were observed at month 1 or month 3 compared with placebo.
In addition, no significant differences were observed in participants in the daridorexant 10-mg group for WASO, LPS, or self-reported total sleep time at month 1 or month 3, compared with the placebo group.
Adverse event rates were similar in the treatment groups (116 participants [38%] in the daridorexant 50-mg group, 117 [38%] in the daridorexant 25-mg group, and 105 [34%] in the placebo group in study 1; and 121 participants [39%] in the daridorexant 25-mg group, 117 [38%] in the daridorexant 10-mg group, and 100 [33%] in the placebo group in study 2. Nasopharyngitis and headache were the most frequently occurring events.
The researchers noted that the study population may not be representative of general insomnia patients because their insomnia might be more severe than is generally observed in practice. Also, most participants were White, patients with comorbidities were not included, and the duration of the studies was 3 months.
“Improvements in sleep variables were achieved without excess sleepiness the following morning, and improvements in daytime functioning were observed,” the researchers stated. “The improvement in sleep perceived by participants in these studies was consistent with that objectively measured by polysomnography.”
Disclosure: This research was funded by Idorsia Pharmaceuticals. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Mignot E, Mayleben D, Fietze I, et al. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. Published online February 1, 2022. doi:10.1016/S1474-4422(21)00436-1