To evaluate the pharmacokinetics and dose proportionality of FT218, an investigational once-nightly sodium oxybate formulation

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 study was an open-label, single-dose, 3-sequential period study in 20 healthy volunteers. Subjects received 3 separate single-dose (without titration)  administrations of FT218 at bedtime, two hours post-evening meal, in a sequential order of 4.5g, 7.5g and 9g with a minimum 7-day washout between doses.  Dose proportionality between the three doses was assessed using the power method.

For the 3 doses, mean pharmacokinetics exhibited similar overall profiles with median T_max between 1.5 and 2 hours. Mean C_max increased from 42.9 to 84.5 µg/mL across the increasing doses. Following C_max, blood levels gradually decreased overnight. Mean concentrations at 8 hours were 4.8, 19.7 and 25.5 µg/mL for the 4.5, 7.5 and 9g doses respectively. The slope estimates were 1.02 (90% CI: 0.84-1.21) and 1.34 (90% CI: 1.17 -1.46) for C_max and AUC_inf respectively. FT218 was generally safe and well-tolerated. The most common AEs were vomiting, nausea, diarhea and headache.

FT218 achieved blood level profiles, when given at bedtime, that are needed for a single nighttime sodium oxybate dose. FT218 was dose proportional for C_max across the dosage range and slightly higher than dose proportional for AUC_inf. 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.