Composite response with once-nightly sodium oxybate: symptom improvement in participants with narcolepsy type 1 in REST-ON

Document Type

Conference Proceeding

Publication Date

2-1-2024

Publication Title

Sleep Med

Abstract

Introduction: A novel once-nightly formulation of sodium oxybate (ON-SXB; FT218; LUMRYZ™) was investigated in patients with narcolepsy type 1 (NT1) and 2 (NT2) in the phase 3 REST-ON trial. ON-SXB treatment resulted in statistically significant improvements vs placebo for the coprimary endpoints of change from baseline in mean sleep latency on the Maintenance of Wakefulness test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and number of weekly cataplexy attacks, as well as the secondary endpoint of improved excessive daytime sleepiness (EDS) using the Epworth Sleepiness Scale (ESS; all P<0.001 vs placebo). ON-SXB was well tolerated; most common adverse drug reactions were dizziness, nausea, vomiting, headache, and enuresis (consistent with the known safety profile of sodium oxybate). The objective of this responder analysis was to assess the proportion of participants with NT1 achieving clinically significant improvement on a composite of these endpoints. Materials and Methods: REST-ON was a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT02720744) designed to evaluate the efficacy and safety of ON-SXB for the treatment of narcolepsy. Participants (aged ≥16 years with NT1 or NT2) who had continuing presence of excessive daytime sleepiness (sleep latency <11 min on the MWT and ESS score >10) and continuing cataplexy (average of 8 episodes/week) were randomly assigned to ON-SXB or placebo. Doses were 4.5 g week 1; 6 g weeks 2−3; 7.5 g weeks 4−8; and 9 g weeks 9−13. This post hoc analysis examined the proportion of participants with NT1 who had clinically significant improvement according to thresholds defined in the 2021 American Academy of Sleep Medicine Clinical Practice Guidelines in 2, 3, or all 4 of the following endpoints: MWT (2-min improvement), CGI-I (1-point improvement), cataplexy (25% decrease), or ESS (2-point improvement) for each of the doses examined. Results: The mean age of participants with NT1 was 32.1 years, 72.8% were female, and most were white (76.5%). The modified intent-to-treat population included 145 participants with NT1 (ON-SXB, n=73; placebo, n=72). At week 3 (6 g), more participants treated with ON-SXB vs placebo had clinical improvement in ≥2 endpoints (79.5% vs 48.6%; all P<0.01), ≥3 endpoints (54.8% vs 25.0%; P<0.001), and in all 4 endpoints (28.8% vs 11.1%; P=0.012). At week 8 (7.5 g), more participants treated with ON-SXB vs placebo had clinical improvement in ≥2 endpoints (86.4% vs 59.4%; P<0.01), ≥3 endpoints (62.1% vs 31.9%; P<0.001), and in all 4 endpoints (33.3% vs 10.1%; P<0.001). At week 13 (9.5 g), more participants treated with ON-SXB vs placebo had clinical improvement in ≥2 endpoints (87.3% vs 62.9%; P<0.01), ≥3 endpoints (76.4 vs 43.5%; P<0.001), and in all 4 endpoints (47.3% vs 14.5%; P<0.001). Conclusions: These data support the robust clinical efficacy of ON-SXB, a once-at-bedtime oxybate for treatment of cataplexy or EDS in adults with narcolepsy, using multiple disease state metrics compared with placebo. Acknowledgements: This study was funded by Avadel Pharmaceuticals.

Volume

115

First Page

210

Last Page

211

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