0573 Application of AASM Clinical Significance Thresholds to Once-Nightly Sodium Oxybate for Improvement in Narcolepsy Symptoms

Abstract Introduction Once-nightly sodium oxybate (ON-SXB; FT218), an investigational, extended-release treatment, was evaluated for the treatment of narcolepsy in adults phase 3 REST-ON clinical trial (NCT02720744). The co-primary endpoints, mean sleep latency on Maintenance Wakefulness Test (MWT), Clinical Global Impression-Improvement rating, and weekly number cataplexy attacks (NCA), secondary endpoint Epworth Sleepiness Scale (ESS) score were significant ON-SXB vs placebo at weeks (6-g dose), 8 (7.5-g 13 (9-g dose; all P< 0.001). These data published after cutoff inclusion American Academy Sleep Medicine (AASM) practice guidelines treatment; thus, results analyzed according to AASM significance thresholds (CSTs). Methods Individuals with type 1/2 age ≥16 years randomized 1:1 receive double-blind (4.5 g, 1 week; 6 2 weeks; 7.5 5 9 weeks) or matching placebo. For each dose (6 week 3; 8; 13), least-squares (LSM) difference from calculated change baseline MWT, ESS score, percentage reduction NCA. As defined 2021 guidelines, CSTs following changes placebo: ≥2-minute increase; ESS, ≥2-point decrease; cataplexy, ≥25% decrease Results 190 participants (ON-SXB, n=97; placebo, n=93) modified intent-to-treat population. On LSM 5.0, 6.2, 6.1 minutes 6, 7.5, g respectively. Differences scores −2.1, −3.2, −3.9 NCA 26.0%, 34.2%, 36.1% Conclusion Clinically improvement excessive daytime sleepiness per AASM-established criteria met doses. If FDA approved, will provide a once-nightly improving EDS narcolepsy. Support (if any) Avadel Pharmaceuticals