Long-Term Safety of Once-Nightly Sodium Oxybate: Interim Analysis of Data From RESTORE (P5-13.005)

Abstract

<h3>Objective:</h3> The objective of RESTORE (NCT04451668) is to assess the long-term safety and tolerability of once-nightly sodium oxybate (ON-SXB; FT218), an investigational extended-release formulation. Interim safety data are reported; dose titration and patient preference data are presented separately. <h3>Background:</h3> In the pivotal phase 3 REST-ON trial (NCT02720744), ON-SXB met its 3 coprimary efficacy endpoints for treatment of adults with narcolepsy (<i>P</i>&lt;0.001 vs placebo) and had a safety profile consistent with that of immediate-release (IR) SXB. RESTORE is an ongoing open-label extension/switch study. <h3>Design/Methods:</h3> Participants aged ≥16 years with narcolepsy type 1/2 who completed the REST-ON trial, were on stable-dose IR oxybate for ≥1 month, or were oxybate-naive were eligible to enroll in RESTORE. Initial ON-SXB doses are equivalent/closest to previous total nightly dose of IR oxybate (switch participants) or 4.5 g/night (other participants); weekly ON-SXB dose adjustments were allowed at 1.5 g/week increments (maximum, 9 g/night). Safety data for participants who received ≥1 dose of ON-SXB as of 01July2022 are reported. <h3>Results:</h3> This analysis includes 180 individuals (REST-ON participants, n=15 [8.3%]; oxybate-naive, n=35 [19.4%]; switch, n=130 [72.2%]; white, n=150 [83.3%]; female, n=122 [67.8%]; mean age, 35 y [range, 16–84]). Adverse events (AEs) were reported by 105 (58.3%) participants. Serious AEs were recorded in 3 participants (abscess; deep vein thrombosis; rib fracture and pneumothorax); all were deemed unrelated to ON-SXB and did not result in study discontinuation. Seventy-six (42.2%) participants reported an adverse drug reaction (ADR), ie, AE related/possibly related to ON-SXB. The most common ADRs (≥3%) were nausea (11.7%), somnolence (6.7%), headache (5%), enuresis (5%), somnambulism (3.9%), dizziness (3.9%), tremor (3.9%), and vomiting (3.3%). Six (3.3%) participants discontinued due to ADRs. <h3>Conclusions:</h3> Thus far in RESTORE, ON-SXB is generally well tolerated, and no new safety signals have been observed. If approved, ON-SXB will offer a once-nightly oxybate treatment option for adults with narcolepsy. <b>Disclosure:</b> Dr. Stern has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel Pharmaceutical. Dr. Stern has received intellectual property interests from a discovery or technology relating to health care. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharma. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Harmony biosciences. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eisai . Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Inspire. The institution of Dr. Roy has received research support from Jazz . The institution of Dr. Roy has received research support from Inspire. The institution of Dr. Roy has received research support from Avadel. Colin Shapiro has nothing to disclose. Dr. Harsh 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. The institution of Dr. Ibrahim has received research support from Avadel. The institution of Dr. Ibrahim has received research support from NIH. Dr. Seiden has received personal compensation for serving as an employee of Avadel Pharmaceuticals. Dr. Seiden has received stock or an ownership interest from Avadel Pharmaceuticals. Dr. Dubow has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Paragon Biosciences. Dr. Dubow has stock in Avadel Pharmaceuticals. Miss Gudeman has received personal compensation for serving as an employee of Avadel Pharmaceuticals. Miss Gudeman has stock in Avadel Pharmaceuticals.