0504 Efficacy and Safety of Seltorexant in Insomnia Disorder

Abstract Introduction Insomnia disorder affects 3-6% of the population and includes functional impairing symptoms for ≥3 months. Current hypnotics have limitations (eg fall risk, dependency, parasomnia, cognitive impairment). In a previous proof-of-concept study, seltorexant, a selective orexin-2 receptor antagonist, dosed at 40mg nightly improved sleep efficiency, latency to persistent sleep (LPS), and wake after sleep onset (WASO) versus placebo. Methods A multicenter, double-blind, randomized, parallel-group, active- and placebo-controlled, 14-day, dose-finding study (NCT03375203) assessed the efficacy and safety of seltorexant in adult and elderly subjects meeting DSM-5 insomnia disorder criteria. Subjects were randomized (1:1:1:1:1 ratio) to: placebo, seltorexant 5mg, 10mg, 20mg, or zolpidem. Primary endpoint: Based on PSG, dose response in LPS change on Night 1 relative to baseline. Secondary endpoints included change from baseline in: WASO over the first 6 hours (WASO-6) on Night 1, and LPS and WASO-6 on Night 13. Multiple Comparison Procedure-Modeling, ANCOVA and MMRM were used for data analyses. Results 365 patients were randomized and 347 (95%) completed the double-blind phase with 68% women and median age of 59yr (22 to 84yr). Statistically significant dose-response relationship (p-value <0.001) was observed for LPS at Night 1 (5mg=12%, 10mg=36%, 20mg=49% improvement compared with placebo). Similar findings were observed for WASO-6 and benefits sustained from Night 1 to 13. The 20 mg dose showed greater improvement than zolpidem on LPS at Nights 1 and 13 and on WASO-6 at Night 13. Overall treatment-emergent adverse events rates were comparable in the seltorexant, placebo, and zolpidem treatment groups. Conclusion Statistically significant and clinically meaningful improvements on LPS & WASO-6 were observed for seltorexant 10 and 20mg dose groups versus placebo. No safety concerns were observed. Seltorexant with its novel mechanism holds potential as a new treatment for insomnia disorder. Support