Polysomnographic Measures of Sleep Continuity in Patients With Narcolepsy: Results From the REST-ON Trial, a Pivotal Phase 3 Study of FT218, a Once-Nightly Sodium Oxybate Formulation (2461)

Objective: To evaluate the efficacy of FT218, a once-nightly sodium oxybate (SO) formulation, on polysomnographic (PSG) measures of disturbed nocturnal sleep (DNS), including number of arousals (NAs), in patients with narcolepsy types 1 and 2. Background: DNS is inherent to narcolepsy and is characterized by fragmented sleep, including frequent, brief nightly awakenings. FT218 is an investigational once-nightly controlled-release formulation of SO, with potential to improve sleep disruption based on its unique extended-release profile. Design/Methods: This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group study in patients with narcolepsy ≥16 years old (randomized, n=212). The 4-period uptitration dosing schedule was as follows: 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks (total study duration, 17 weeks). PSG measures, as secondary endpoints, were DNS, defined as shifts to wake or N1 from N1, N2, N3, and REM. NAs were defined per AASM Scoring Manual (v2.6). Results: LS mean difference between FT218 and placebo for DNS was significant (P Conclusions: FT218 demonstrated significant consolidation of sleep vs placebo at all doses tested (9, 7.5, and 6 g). FT218 was generally well tolerated, and the most common adverse reactions were well-known and established SO adverse reactions. FT218 could offer a new once-nightly treatment option for disrupted nighttime sleep in patients with narcolepsy as demonstrated by PSG measures. Disclosure: Yves Dauvilliers has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for idorsia. Yves Dauvilliers has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for JAZZ. Yves Dauvilliers has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Thorpy has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Jazz. Dr. Roth has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Takeda. Dr. Roth has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Avadel. Dr. Roth has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Jazz. Mr. Rosenberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. The institution of Mr. Rosenberg has received research support from Eisai. BC Corser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eisai. BC Corser has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. BC Corser has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Harmony. Colin Shapiro has nothing to disclose. Akinyemi Ajayi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz Pharmaceutical. Akinyemi Ajayi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharmaceutical. Dr. Dubow has received personal compensation for serving as an employee of Avadel Pharmaceuticals. Dr. Dubow has received stock or an ownership interest from Avadel Pharmaceuticals. Dr. Seiden has received personal compensation for serving as an employee of Avadel Pharmaceuticals. Dr. Seiden has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Physician’s Seal. Dr. Seiden has received stock or an ownership interest from Avadel Pharmaceuticals. Dr. Kushida has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avadel. Dr. Kushida has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Kushida has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for XW Pharma, Inc.. Dr. Kushida has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Samsung. Dr. Kushida has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zephyr Sleep Technologies. Dr. Kushida has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck & Co., Inc.. Dr. Kushida has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for State of Arizona. Dr. Kushida has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Browne George Ross, LLP. The institution of Dr. Kushida has received research support from AmCAD, Philips-Respironics, Asate, Syneos Health, Inspire. Dr. Kushida has received publishing royalties from a publication relating to health care.