To evaluate the efficacy of FT218, a once-nightly sodium oxybate (SO) formulation, on polysomnographic (PSG) measures of disturbed nocturnal sleep (DNS), including number of arousals (NAs), in patients with narcolepsy types 1 and 2.

DNS is inherent to narcolepsy and is characterized by fragmented sleep, including frequent, brief nightly awakenings. FT218 is an investigational once-nightly controlled-release formulation of SO, with potential to improve sleep disruption based on its unique extended-release profile.

This was a randomized, double-blind, placebo-controlled, multicenter, parallel-group study in patients with narcolepsy ≥16 years old (randomized, n=212). The 4-period uptitration dosing schedule was as follows: 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks (total study duration, 17 weeks). PSG measures, as secondary endpoints, were DNS, defined as shifts to wake or N1 from N1, N2, N3, and REM. NAs were defined per AASM Scoring Manual (v2.6).

LS mean difference between FT218 and placebo for DNS was significant (P<0.001) at all doses tested: –22.63 at 9 g (week 13), –17.70 at 7.5 g (week 8), and –11.00 at 6 g (week 3). LS mean difference between FT218 and placebo for NAs was –23.68 (P<0.001) at 9 g, –19.41 (P<0.001) at 7.5 g, and –11.29 (P<0.021) at 6 g. Most common adverse reactions with FT218 treatment were nausea, dizziness, enuresis, headache, decreased appetite, and vomiting.

FT218 demonstrated significant consolidation of sleep vs placebo at all doses tested (9, 7.5, and 6 g). FT218 was generally well tolerated, and the most common adverse reactions were well-known and established SO adverse reactions. FT218 could offer a new once-nightly treatment option for disrupted nighttime sleep in patients with narcolepsy as demonstrated by PSG measures.