Magnitude of improvement in excessive daytime sleepiness with the once-at-bedtime oxybate for narcolepsy

Document Type

Conference Proceeding

Publication Date

2-1-2024

Publication Title

Sleep Med

Abstract

Introduction: The safety and efficacy of once-nightly sodium oxybate (ON-SXB; FT218; LUMRYZ™) was investigated in the phase 3 REST-ON trial. Study results demonstrated statistically significant improvements for the coprimary endpoints of change from baseline in mean sleep latency on the Maintenance of Wakefulness test, Clinical Global Impression-Improvement (CGI-I) rating, and weekly cataplexy attacks for ON-SXB 6 g (week 3), 7.5 g (week 8), and 9 g (week 13) vs placebo (all P<0.001). Participants also had statistically significant improvements in excessive daytime sleepiness (EDS) measured using the Epworth Sleepiness Scale (ESS; secondary endpoint) at all doses beginning at week 2 (post hoc analysis, ON-SXB 6 g vs placebo at week 2). The objective of this analysis was to assess the magnitude of improvement in the patient-reported outcome of EDS following treatment with ON-SXB. Materials and Methods: In this multicenter, double-blind, placebo-controlled REST-ON clinical trial (NCT02720744), participants aged ≥16 years with narcolepsy type 1 (NT1) or 2 (NT2) were randomly assigned 1:1 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 median (Q1-Q3; interquartile range [IQR]) ESS scores to assess magnitude of improvement in EDS at the end of each dosing period. Results: The mean age of participants was 31.2 years, 68% were female, 75.5% were white, and 76.4% had NT1. The modified intent-to-treat population included 190 participants (ON-SXB, n=97; placebo, n=93). Baseline median (IQR) ESS scores were 17 (14−19) for ON-SXB and 18 (15−21) for placebo. After 1 week of treatment, median (IQR) ESS scores were 16 (12−18) for ON-SXB 4.5 g vs 17 (13−20) for placebo. At week 3 (ON-SXB 6 g), median (IQR) ESS scores were 14 (10−18) vs 17 (14−20) for placebo. With the 7.5-g dose of ON-SXB at week 8, median (IQR) ESS scores were 12 (8−16) vs 15.5 (12−20) for placebo. At the end of the study (week 13), median (IQR) ESS scores for ON-SXB 9.0 g were 9.5 (6.0−15.0) vs 15 (11−19) for placebo. ON-SXB was well tolerated; the most common adverse drug reactions were dizziness, nausea, vomiting, headache, and enuresis (consistent with the known safety profile of sodium oxybate). Conclusions: Treatment with ON-SXB resulted in statistically significant and clinically meaningful improvement in EDS with doses >6 g in that at the end of the study, median ESS scores were within the range considered normal (≤10). ON-SXB should be considered an effective intervention in treatment of EDS for patients with NT1 or NT2 with a once-at-bedtime dose. Acknowledgements: This study was funded by Avadel Pharmaceuticals.

Volume

115

First Page

221

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