0575 Cataplexy Response With FT218 (Once-Nightly Sodium Oxybate): Post Hoc Responder Analysis From the Phase 3 Rest-ON Clinical Trial

Abstract

Abstract Introduction In the phase 3 REST-ON trial (NCT02720744), participants with narcolepsy type 1 (NT1) treated with once-nightly sodium oxybate (ON-SXB; FT218), an investigational, extended-release formulation, had significant reductions in cataplexy episodes (ON-SXB vs placebo: 4.5 g, P< 0.05 [post hoc]; 6 , 7.5, and 9 g, all P< 0.001). This post hoc responder analysis further characterized improvements in mean weekly cataplexy episodes in trial participants. Methods In REST-ON, participants aged ≥16 years with NT1/NT2 were randomized 1:1 to double-blind ON-SXB or placebo for 13 weeks. Participants took 4.5 g (1 week), 6 g (2 weeks), 7.5 g (5 weeks), and 9 g (5 weeks). Participants with NT1 recorded number of cataplexy episodes per day (0, 1, 2, 3, 4, or ≥5) in a diary. Percentage of participants with ≥25%, ≥50%, ≥75%, and 100% reductions in weekly cataplexy episodes from baseline were compared (ON-SXB vs placebo; Fisher exact test). Results In the modified intent-to-treat population, 145 participants had NT1 (ON-SXB, n=73; placebo, n=72). Baseline mean (SD) number of weekly cataplexy episodes was 18.9 (8.7) for the ON-SXB group and 19.8 (8.9) for placebo. At week 1 (4.5 g), significantly more participants taking ON-SXB had ≥25% reduction in cataplexy (43.8% vs 26.4%; P< 0.05). Significantly more participants receiving ON-SXB had ≥25%, ≥50%, or ≥75% reduction in cataplexy vs placebo at weeks 3, 8, and 13 and complete resolution of cataplexy at weeks 8 and 13 (6-g dose: ≥25%, 68.5% vs 40.3% [P< 0.001]; ≥50%, 38.4% vs 20.8% [P< 0.05]; ≥75%, 23.3% vs 4.2% [P=0.001]; 100%, 2.7% vs 0 [P=NS]; 7.5-g dose: ≥25%, 67.1% vs 43.1%; ≥50%, 53.4% vs 25.0%; ≥75%, 32.9% vs 8.3% [all P< 0.001]; 100%, 6.8% vs 0 [P< 0.05]; 9-g dose: ≥25%, 58.9% vs 41.7% [P< 0.001]; ≥50%, 49.3% vs 26.4% [P< 0.001]; ≥75%, 32.9% vs 15.3% [P< 0.01]; 100%, 11.0% vs 2.8% [P< 0.05]). Conclusion In this post-hoc analysis, ON-SXB 4.5 g significantly reduced cataplexy by week 1. Additionally, ~10% of participants taking ON-SXB 7.5 and 9 g were free of cataplexy episodes. These data may be useful for clinicians when setting expectations of ON-SXB effectiveness for patients with cataplexy. Support (if any) Avadel Pharmaceuticals