To evaluate the relative bioavailability of investigational once-nightly sodium oxybate, FT218,  6 g, compared to commercially available twice-nightly sodium oxybate and the food effect of FT218

Sodium oxybate is an effective treatment for excessive daytime sleepiness and cataplexy in patients with narcolepsy. The approved forumulation requires twice-nightly dosing - at bedtime and 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

Two crossover, single-dose pharmacokinetic studies were conducted in healthy volunteers. The first, a relative bioavailability study (n=28) was completed comparing FT218 6 g to twice-nightly sodium oxybate 6 g (in two divided doses of 3 g). The second, evaluated the food effect (n=16) of FT218 6g in the Fed vs. Fasted state.

FT218 had a lower overall C_max than twice-nightly sodium oxybate, while AUC was equivalent. C_8h level and variability was comparable between FT218 and twice-nightly sodium oxybate. In the Fed, compared to the Fasted state, FT218 had a longer T_max, lower C_max and decreased AUC (C_max 67%, AUC 86%, T_max 1-hour slower than Fasted values). Adverse Events with FT218 were mostly mild or moderate in severity, non-serious and known AEs associated with sodium oxybate. The safety profiles of FT218 and twice-nightly sodium oxybate at 6 g appeared similar.

Once-nightly FT218 at 6 g demonstrated a lower overall C_max and similar exposure to twice-nightly sodium oxybate, with similar C_8h plasma levels and C_8h variability. In the Fed state, AUC and Cmax of FT218 was lower than in the Fasted State. FT218 was generally safe and well tolerated and the safety profile appeared comparable to twice-nightly sodium oxybate. 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.