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

Keywords

oxybate sodium, placebo, adult, adverse drug reaction, aged, bedtime, bedtime dosage, cataplexy, Caucasian, Clinical Global Impression-improvement scale, clinical trial, conference abstract, controlled study, dizziness, double blind procedure, drug therapy, enuresis, Epworth sleepiness scale, excessive daytime sleepiness, female, headache, human, intention to treat analysis, maintenance of wakefulness test, major clinical study, male, multicenter study, narcolepsy, narcolepsy with cataplexy, nausea and vomiting, patient-reported outcome, phase 3 clinical trial, post hoc analysis, randomized controlled trial, side effect, sleep latency

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

Find It @ Sladen

Share

COinS