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.

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.

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.

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.

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.