Efficacy of Once-nightly Sodium Oxybate (ON-SXB; FT218) for Excessive Daytime Sleepiness and Cataplexy: Post-hoc Number Needed to Treat and Effect Size Analyses From REST-ON

Document Type

Conference Proceeding

Publication Date

5-22-2022

Publication Title

Sleep Med

Keywords

oxybate sodium, placebo, adult, calculation, cataplexy, Clinical Global Impression scale, clinical trial, conference abstract, controlled study, dose response, drug efficacy, drug therapy, effect size, Epworth sleepiness scale, excessive daytime sleepiness, expectation, female, human, major clinical study, male, narcolepsy, numbers needed to treat, phase 3 clinical trial, post hoc analysis, randomized controlled trial, sleep latency, wakefulness

Abstract

Introduction: Narcolepsy is a chronic neurologic disease; symptoms include excessive daytime sleepiness (EDS) and cataplexy. FT218 is an extended-release, once-nightly formulation of sodium oxybate (ON-SXB) that is in development for treatment of adults with narcolepsy. Treatment with ON-SXB resulted in significant improvement vs placebo (6 g, 7.5 g, and 9 g, all P<0.001) for the coprimary endpoints of mean sleep latency on the Maintenance of Wakefulness test (MWT), Clinical Global Impression of Improvement rating, and number of weekly cataplexy episodes, as well as the secondary endpoint Epworth sleepiness scale (ESS) score, in the phase 3 REST-ON clinical trial (NCT02720744). Post-hoc analyses of numbers needed to treat (NNT) and effect sizes were performed to provide further context into the effectiveness of ON-SXB. Materials and Methods: Individuals aged ≥16 years with narcolepsy type 1 or 2 were randomized 1:1 to receive ON-SXB (1 week, 4.5 g; 2 weeks, 6 g; 5 weeks, 7.5 g; 5 weeks, 9 g) or placebo. For the post-hoc analyses, response on the MWT was defined as ≥5 min increase from baseline in mean sleep latency, response on the ESS was defined as a score ≤10, and cataplexy response was defined as ≥50% reduction from baseline in the mean number of weekly. Results:In total, 222 participants were randomized and 190 comprised the modified intent-to-treat population (ON-SXB, n=97 [NT1, n=73]; placebo, n=93 [NT1, n= 72]). For MWT response, all doses of ON-SXB (6 g at week 3, 7.5 g at week 8, and 9 g at week 13) had NNTs of 3 and effect sizes ranging from 0.7–0.9. For ESS response, NNTs ranged from 3 to 6, with a dose-response effect. As a decrease signifies response, effect sizes were between –0.5 to –0.7 for the 3 doses. For cataplexy response, NNT was 6 for the 6-g dose and 3 for the 7.5-g and 9-g doses, and the effect sizes were between –0.7 to –0.8. Conclusions: NNTs provide a useful interpretation of the expected effectiveness of a medication. As defined by these measures, only 3–6 patients need to be treated with ON-SXB to achieve ≥5 minutes increased sleep latency on the MWT or an ESS of ≤10, with the same number needed to achieve a 50% or greater reduction in cataplexy. Effect size provides a useful interpretation, as this calculation relies upon the standard deviation; an effect size of 0.50 or more is generally regarded as a moderate effect and 0.80 as a large effect. These post-hoc analyses provide further confidence in the strength of ON-SXB efficacy and may be useful to clinicians in discussing treatment expectations. Acknowledgements: This study was funded by Avadel Pharmaceuticals.

Volume

100

First Page

S128

Last Page

S129

Find It @ Sladen

Share

COinS