0833 Long-Term Safety and Tolerability of Once-Nightly Sodium Oxybate: A Post Hoc Analysis from RESTORE Free

Abstract

Introduction

Once-nightly sodium oxybate (ON-SXB; LUMRYZ™) is an extended-release formulation of sodium oxybate that eliminates the second, middle-of-the-night dose required by immediate-release twice-nightly oxybate (TN-OXB) formulations. RESTORE (NCT04451668) was an open-label/switch study evaluating the long-term safety/tolerability of ON-SXB in people with narcolepsy.

Methods

Participants ≥16 years of age with narcolepsy who had completed the phase 3 REST-ON trial, were on stable-dose TN-OXB (switch participants), or were oxybate-naïve were eligible for RESTORE. Switch participants’ initial ON-SXB doses were equivalent/closest to their prior total nightly TN-OXB dose. After participants titrated their ON-SXB dose (±1.5 g/week; maximum, 9 g/night) with no tolerability issues for ≥3 months, participants entered the stable dosing period. Treatment-emergent adverse events (TEAEs) were recorded quarterly for switch participants in the safety population (all participants who received ≥1 dose of ON-SXB).

Results

A total of 130 switch participants were included in the safety population and received ON-SXB for a median (range) duration of 502.5 (8-1169) days during the >3-year study. Of these participants, 115 continued into the stable dosing period and were included in this analysis. Of the 115 who entered the stable dosing period, 73.9% (85/115) reported ≥1 TEAE. TEAEs reported by ≥3% of participants included COVID-19 (18.3%), nasopharyngitis (11.3%), nausea (10.4%), sinusitis (8.7%), fall (8.7%), headache (7.0%), enuresis (7.0%), cough (6.1%), upper respiratory tract infection (5.2%), urinary tract infection (5.2%), somnolence (4.3%), tremor (4.3%), vomiting (3.5%), dyspnea (3.5%), rash (3.5%), decreased appetite (3.5%), hypertension (3.5%), concussion (3.5%), and contusion (3.5%). Eight (7%) participants reported ≥1 serious TEAE (events, n=10); of these, 2 serious TEAEs were deemed related to ON-SXB (gastroesophageal reflux disease and cataplexy). Five participants (4.3%) experienced ≥1 TEAE that led to ON-SXB discontinuation (upper abdominal pain, fatigue, fall, dizziness, paresthesia, irritability, nightmare, and hypertension; n=1 [0.9%] each).

Conclusion

Reported AEs were consistent with the known AEs of oxybates. Only 4% of participants discontinued owing to a TEAE during the stable dosing period, underscoring the largely transient nature of AEs and the long-term tolerability of ON-SXB.

Support (if any)

Avadel Pharmaceuticals