491 Efficacy of FT218, a Once-Nightly Sodium Oxybate Formulation, by Narcolepsy Subtype: 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 subtypes 1 (NT1) and 2 (NT2). Methods This was a randomized, double-blind, placebo-controlled, multicenter study in patients with narcolepsy ≥16 years old. Patients were stratified by narcolepsy subtypes 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 (NT1: FT218, n=72; placebo, n=73; NT2: FT218, n=21, placebo, n=24). Patients with NT1 or NT2 receiving FT218 had significant improvement in MWT. LS mean difference in mean sleep latency (minutes) vs placebo for NT1 was 5.97 for 9.0 g (week 13), 7.02 for 7.5 g (week 8), and 4.89 for 6.0 g (week 3; all P<0.001), and for NT2, 6.27 for 9.0 g (P=0.020), 4.01 for 7.5 g (P=0.162), and 5.33 for 6.0 g (P=0.020). A higher proportion of NT1 patients receiving FT218 had significant improvement on CGI-I vs placebo (9.0 g: 75.5% vs 35.9%; 7.5 g: 66.9% vs 27.9%; 6.0 g: 39.9% vs 7.8%; all P<0.001). A higher number of NT2 patients receiving FT218 were consistently rated as much/very much improved vs placebo, based on descriptive statistics. FT218 was generally well tolerated. Conclusion FT218 had similar efficacy on EDS at evaluated doses in NT1 and NT2, with improvement in MWT and CGI-I greater than placebo. FT218 may provide effective treatment for EDS in patients with narcolepsy, with or without cataplexy. Support (if any) Avadel Pharmaceuticals.