Long-Term Safety of Once-Nightly Sodium Oxybate: Interim Analysis of Data From RESTORE
Thomas Stern1, Asim Roy2, Colin Shapiro3, John Harsh4, Akinyemi Ajayi5, Sally Ibrahim6, David Seiden7, Jordan Dubow7, Jennifer Gudeman7
1Advanced Respiratory and Sleep Medicine, PLLC, 2Ohio Sleep Medicine and Neuroscience Institute, 3University of Toronto, 4Colorado Sleep Institute, 5Florida Pediatric Research Institute, 6University Hospitals Cleveland Medical Center, 7Avadel Pharmaceuticals
Objective:

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.

Background:

In the pivotal phase 3 REST-ON trial (NCT02720744), ON-SXB met its 3 coprimary efficacy endpoints for treatment of adults with narcolepsy (P<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.

Design/Methods:

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.

Results:

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.

Conclusions:

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.

10.1212/WNL.0000000000201923