0835 Improvement of Individual Excessive Daytime Sleepiness Symptoms with Once-Nightly Sodium Oxybate for Narcolepsy Free

Abstract

Introduction

The Epworth Sleepiness Scale (ESS) is a commonly used 8-item patient-reported outcome measure for excessive daytime sleepiness. While aggregate data are typically presented, individual domains vary in clinical significance. This post hoc analysis from the phase 3 REST-ON trial (NCT02720744) evaluated the efficacy of once-nightly sodium oxybate (ON-SXB; LUMRYZ™) on individual ESS domains.

Methods

Participants aged ≥16 years with narcolepsy were randomized 1:1 to ON-SXB (week 1, 4.5 g; weeks 2–3, 6 g; weeks 4–8, 7.5 g; weeks 9–13, 9 g) or placebo. ESS data from the modified intent-to-treat population (mITT; ≥1 efficacy measurement after receiving the 6-g dose) at weeks 3, 8, and 13 were analyzed.

Results

In the mITT population (ON-SXB, n=97; placebo, n=93), ON-SXB was associated with significant sleepiness improvements vs placebo for sitting and reading, watching TV, lying down to rest in the afternoon, and sitting quietly after lunch; all doses P< 0.01. ON-SXB was associated with significant sleepiness improvement vs placebo as a passenger in a car for an hour without a break (least squares mean difference [LSMD; 95% CI] in change from baseline: 6 g, –0.39 [–0.61 to –0.17]; 7.5 g, –0.59 [–0.85 to –0.32]; 9 g, –0.67 [–0.95 to –0.38]; all doses P< 0.001). Significant sleepiness improvements were observed with 7.5-g and 9-g ON-SXB when sitting inactive in public (LSMD vs placebo [95% CI]: 7.5 g, –0.34 [–0.61 to –0.07], P=0.014; 9 g, –0.44 [–0.71 to –0.18], P=0.001) and sitting and talking to someone (7.5 g, –0.29 [–0.47 to –0.11], P=0.002; 9 g, –0.24 [–0.44 to –0.04], P=0.018). Significant sleepiness improvement as a driver stopped in traffic was observed with 9-g ON-SXB (LSMD vs placebo [95% CI], –0.35 [–0.63 to –0.07]; P=0.015).

Conclusion

At all ON-SXB doses, participants had significant improvements vs placebo in sleepiness while completing routine activities. The greatest improvements in these activities were observed with the 9-g ON-SXB dose, including the domain for sleepiness as a driver stopped in traffic, a key safety concern. ON-SXB may be helpful in addressing safety challenges for people with narcolepsy.

Support (if any)

Avadel Pharmaceuticals