Seltorexant Achieves Primary, Secondary Endpoints in Insomnia

Thomas Roth, PhDDirector of the Sleep Disorders and Research Center at Henry Ford Hospital

Thomas Roth, PhD

The results of a recent phase 2b clinical trial (ISM2005) show that seltorexant (min-202) demonstrated highly statistically significant (P <.001) and clinically meaningful improvement on latency to persistent sleep at night 1 in patients with insomnia.

The multicenter, double-blind, randomized, active- and placebo-controlled, 17-day dose-finding study was designed to evaluate the efficacy and safety of seltorexant in both adult and elderly subjects with insomnia without psychiatric comorbidity.

“The findings from this study demonstrate that seltorexant significantly improves sleep induction and prolongs sleep duration,” Thomas Roth, PhD, director of the sleep disorders and research center, Henry Ford Hospital, said in a statement.¹ “The results also demonstrate that seltorexant showed a significantly greater improvement in these sleep parameters compared to zolpidem.”

The study enrolled 365 subjects that were randomized in a 1:1:1:1:1 ratio to receive 1 of 5 treatments: seltorexant 5 mg, seltorexant 10 mg, seltorexant 20 mg, zolpidem 5 or 10 mg based on the local label, or placebo. The randomization was stratified by region, the United States, Europe, and Japan, and by age group, adult and elderly. Of the 364 subjects that received study drugs, 32.4% were male, and subjects had a mean total insomnia severity index score of 20.2 at baseline.

Efficacy was evaluated at night 1 and 2 weeks after drug administration; safety was assessed throughout the entire study.

The primary endpoint included sleep onset measured by latency to persistent sleep by polysomnography at first drug administration of the 3 doses of seltorexant. The key secondary measure was the effect of seltorexant on Wake After Sleep Onset over first 6 hours (WASO-6) by polysomnography at night 1; additional secondary endpoints included the assessment of the effect of seltorexant on latency to persistent sleep and WASO-6 at night 13, and the effect of seltorexant compared to zolpidem on both latency to persistent sleep and WASO-6 at baseline and night 13.

All 4 prespecified dose-response models showed a significant dose-response relationship in latency to persistent sleep at baseline. Investigators reported a separation from placebo of the seltorexant 10 mg and seltorexant 20 mg groups. The changes of the seltorexant dose group compared to placebo at baseline were 16.4 minutes for the 5 mg, 32.2 minutes for the 10 mg (P ≤.001), and 36.6 minutes for the 20 mg (P ≤.001). A night 13, the following changes were also observed over placebo: 5.2 minutes for the 5 mg group, 28.6 minutes for the 10 mg group (P ≤.001), and 21 minutes for the 20 mg (P ≤.001).¹

The mean decrease from baseline in latency to persistent sleep was 15 minutes for placebo, 30 minutes for seltorexant 5 mg, 50 minutes for 10 mg, and 48 minutes for 20 mg. In the assessment of the WASO-6 at night 1, investigators found that the mean improvement was 15 minutes for placebo, 23 minutes for seltorexant 5 mg, 43 minutes for 10 mg, and 45 minutes for 20 mg.¹

“In addition, the beneficial effects on latency to persistent sleep and WASO of seltorexant on elderly patients in the study, in conjunction with a favorable tolerability profile, suggest its potential benefit in the large and growing population of elderly patients whose prevalence of insomnia is higher than in younger patients, thus representing an important therapeutic option,” Roth added.

Seltorexant demonstrated a good safety and tolerability profile in both patient populations; treatment-emergent adverse effects were similar to those observed in prior studies. In the seltorexant treatment arms, the incidence of adverse effects was low, 33.8% in the combined seltorexant group (40.3% in the 5 mg group, 31.5% in the 10 mg group, and 29.6% in the 20 mg group, and was lower than the placebo rate of 49.3% and zolpidem group of 42.5%. Most treatment-emergent adverse effects were reported as mild to moderate in intensity and resolved without consequence.

REFERENCE

1. Minerva Neurosciences Announces Achievement of Primary and Key Secondary Objectives in Phase 2b Clinical Trial of Seltorexant (MIN-202) in Insomnia [news release]. Waltham, Mass.; Minerva Neurosciences: June 24, 2019. https://www.globenewswire.com/news-release/2019/06/24/1872915/0/en/Minerva-Neurosciences-Announces-Achievement-of-Primary-and-Key-Secondary-Objectives-in-Phase-2b-Clinical-Trial-of-Seltorexant-MIN-202-in-Insomnia.html. Accessed June 24, 2019.