492 Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, by Stimulant Use: A Post Hoc Analysis From the REST-ON Study

Abstract

Abstract Introduction FT218 is an investigational, once-nightly, controlled-release formulation of sodium oxybate for the treatment of narcolepsy. The purpose of this post hoc analysis of the REST-ON study was to evaluate the effect of FT218 on measures of excessive daytime sleepiness (EDS) in patients with narcolepsy with or without stimulant use. Methods This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were stratified by stimulant use and randomized 1:1 to receive FT218 or matching placebo: 4.5 g/night for 1 week, 6.0 g/night for 2 weeks, 7.5 g/night for 5 weeks, and 9.0 g/night for 5 weeks (maximum treatment duration, 13 weeks). Assessments of EDS included mean sleep latency (minutes) on maintenance of wakefulness test (MWT) and Clinical Global Impression-Improvement (CGI-I) in sleepiness. Results A total of 190 patients were included in the modified intent-to-treat population (stimulants: FT218, n=66; placebo, n=53; no stimulants: FT218, n=31, placebo, n=40). Overall, 63% of patients were on concomitant stimulants. Patients receiving FT218 had significant improvement vs placebo in MWT regardless of stimulant use. LS mean difference in mean sleep latency vs placebo for stimulant use was 5.99 for 9.0 g (week 13), 5.51 for 7.5 g (week 8), and 5.35 for 6.0 g (week 3; all P<0.001). For no stimulant use, LS mean difference was 6.28 for 9.0 g (P=0.001), 7.14 for 7.5 g (P<0.001), and 4.19 for 6.0 g (P=0.007). More patients receiving FT218 rated sleepiness as much/very much improved on CGI-I vs placebo (stimulant use: 9.0 g, 80.5% vs 35.3%, odds ratio [OR] 7.55; 7.5 g, 66.3% vs 26.5%, OR 5.44; 6.0 g, 39.8% vs 4.4%, OR 14.27 [all P<0.001]; no stimulant use: 9.0 g, 55.1% vs 27.2%, OR 3.29 [P=0.047]; 7.5 g, 54.5% vs 17.5%, OR 5.64 [P=0.006]; 6.0 g, 40.0% vs 7.7%, OR 8.04 [P=0.003]). FT218 was generally well tolerated. Conclusion FT218 had similar efficacy on EDS at all evaluated doses in narcolepsy patients with or without stimulant use, with improvement over placebo on MWT and CGI-I. FT218 may provide effective treatment for EDS in patients with narcolepsy regardless of stimulant use. Support (if any) Avadel Pharmaceuticals.