Long-Term Safety of Once-Nightly Sodium Oxybate for Narcolepsy: RESTORE Study Interim Analysis of Data

This study was funded by Avadel Pharmaceuticals. Introduction: RESTORE (NCT04451668) is an ongoing open-label/switch study evaluating the safety and tolerability of a once-at-bedtime oxybate (LUMRYZ™ sodium oxybate for extended-release oral suspension, CIII [FT218; once-nightly sodium oxybate (ON-SXB)]). Methods: Participants aged ≥16 years with narcolepsy type 1/2 who completed the phase 3 REST-ON trial, were on stable-dose (≥1 month) immediate-release oxybate, or were oxybate-naive were eligible. Doses were 4.5 g/night or equivalent/closest to previous total oxybate dose/night for those switching; 1.5 g/week adjustments (maximum dose, 9 g/night) were allowed. Safety data are reported. Results: As of March 6, 2023, 180 participants received ≥1 dose of ON-SXB (REST-ON participants, n=15 [8.3%]; oxybate-naive, n=35 [19.4%]; switch, n=130 [72.2%]). 83.3% are white, 67.8% female; mean age, 35 years (range, 16–84). Of 133 participants reporting an adverse event (AE), most had AEs that were mild (38.9%) or moderate (27.2%); 14 experienced a severe AE, 12 experienced an AE leading to discontinuation, and 7 had a serious AE (none occurred in >1 participant). Adverse drug reactions (ADRs; AEs related/possibly related to ON-SXB) were reported by 93 (51.7%) participants. ADRs occurring in ≥3% of participants: nausea (13.3%), somnolence (7.8%), enuresis (6.7%), headache (6.7%), dizziness (5.6%), somnambulism (5.0%), anxiety (3.9%), vomiting (3.9%), paresthesia (3.3%), and tremor (3.3%). Conclusions: Interim data from RESTORE suggest that the safety profile of ON-SXB is consistent with that of SXB. ON-SXB is generally well tolerated; no new safety signals have been observed thus far in RESTORE. ON-SXB offers adults with narcolepsy a once-at-bedtime oxybate treatment option.