To evaluate the pharmacokinetics of three prototypes of investigational once-nightly sodium oxybate, FT218, in a  pilot pharmacokinetic (PK) study

Sodium oxybate is an effective treatment for excessive daytime sleepiness and cataplexy in patients with narcolepsy. The approved effective doses of sodium oxybate are 6, 7.5 and 9 g per night, divided in two doses – the first taken at bedtime and the second 2.5 – 4 hours later. FT218 is a controlled-release formulation of sodium oxybate intended for once-nightly dosing, using Avadel’s proprietary Micropump™ technology

This was an exploratory open label, randomized, crossover study in 16 healthy male and female volunteers. Each  subject received 4 different formulations of sodium oxybate in 4 randomized study periods with a 3 day washout between periods: a single 4.5 g dose of one of the three test formulations of FT218 or 4.5 g (2 X 2.25 g) or twice-nightly commercially available sodium oxybate, given 4-hours apart.

Each of the three FT218 prototypes exhibited a sustained release profile with C_max below the global C_max of twice-nightly sodium oxybate and a C_8h close to the reference values. Prototype 2 exhibited PK characteristics closest to the desired target profile as it exhibited a higher C_max compared to the other prototypes, and the AUC_inf was the closest to the AUC_inf of the twice-nightly formulation. C_8h values were comparable between prototype 2 and twice-nightly sodium oxybate. The safety profile was comparable between all four formulations.

The three prototypes of FT218 exhibited PK profiles covering the entire night, with once-nightly dosing. Prototype 2, compared to twice nightly sodium oxybate IR, exhibited a lower overall C_max, a comparable C_8h, and comparable AUC. The efficacy and safety of FT218 for the treatment of excessive daytime sleepiness and cataplexy in narcolepsy patients is currently being evaluated in the Phase 3 REST-ON pivotal study.