Application of AASM clinical significance thresholds to once-nightly sodium oxybate for improvement in narcolepsy symptoms

Document Type

Conference Proceeding

Publication Date

2-1-2024

Publication Title

Sleep Med

Abstract

Introduction: Extended-release sodium oxybate taken once at bedtime (LUMRYZ™, sodium oxybate for extended-release oral suspension [FT218; once-nightly sodium oxybate (ON-SXB)]), was evaluated for the treatment of narcolepsy in adults in the phase 3 REST-ON clinical trial (NCT02720744). The 3 coprimary endpoints, mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement rating, and weekly number of cataplexy attacks (NCA), and the secondary endpoint of Epworth Sleepiness Scale (ESS) score were significant for ON-SXB vs placebo at weeks 3 (6-g dose), 8 (7.5-g dose), and 13 (9-g dose; all P<0.001) and the treatment was well tolerated (most common adverse drug reactions: dizziness, nausea, vomiting, headache, enuresis). These data were published after the cutoff for inclusion in the 2021 American Academy of Sleep Medicine (AASM) clinical practice guidelines for narcolepsy treatment; thus, REST-ON results were analyzed according to AASM clinical significance thresholds (CSTs). Materials and Methods: Individuals with narcolepsy type 1 [NT1] or 2 [NT2] and age ≥16 years were randomized 1:1 to receive double-blind ON-SXB (4.5 g, 1 week; 6 g, 2 weeks; 7.5 g, 5 weeks; 9 g, 5 weeks) or matching placebo. For each dose (6 g, week 3; 7.5 g, week 8; and 9 g, week 13), least-squares mean (LSM) difference from placebo was calculated for change from baseline in mean sleep latency on the MWT, ESS score, and percentage reduction in NCA. Percentage of participants with improvement (very much/much/minimally improved) on the CGI-I was also calculated. As defined in the 2021 AASM guidelines, CSTs were the following changes from baseline vs placebo: MWT, ≥2-minute increase; ESS, ≥2-point decrease; and cataplexy, ≥25% decrease in NCA. The CST for CGI-I was ≥33% reporting improvement from baseline. Results: 190 participants (ON-SXB, n=97 [NT1, n=73]; placebo, n=93 [NT1, n=72]) were in the modified intent-to-treat population. On the MWT, difference in LSM change from baseline was 5.0, 6.2, and 6.1 minutes for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Differences in LSM change from baseline ESS scores were −2.1, −3.2, and −3.9 for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Differences in LSM percentage reduction in NCA were 26.0%, 34.2%, and 36.1% for ON-SXB 6, 7.5, and 9 g vs placebo, respectively. Percentage of participants with improvement (very much/much/minimally improved) on the CGI-I for ON-SXB 6 g (80.5%), 7.5 g (88.0%), and 9 g (92.8%) met the AASM CST. Conclusions: Clinically significant improvement in excessive daytime sleepiness (EDS), cataplexy, and overall condition per AASM-established criteria was met with ON-SXB 6, 7.5, and 9 g doses. FDA-approved ON-SXB is a once-at-bedtime treatment for improving EDS and cataplexy in adults with narcolepsy. Acknowledgements: This study was funded by Avadel Pharmaceuticals.

Volume

115

First Page

205

Last Page

206

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