Avadel Pharmaceuticals plc, a company focused on developing FT218 for narcolepsy, present two posters at SLEEP 2019. The posters highlight pharmacokinetic (PK) data for its investigational, once-nightly controlled-release sodium oxybate (FT218), including a head-to-head PK comparison to twice-nightly sodium oxybate and dose proportionality across three doses.

“Our once-nightly controlled-release sodium oxybate demonstrated lower overall peak plasma concentrations (Cmax) and similar total exposures (AUC), compared to twice-nightly sodium oxybate in a head-to-head study,” says Jordan Dubow, MD, chief medical officer of Avadel Pharmaceuticals, in a release. “Furthermore, results from our dose proportionality study showed that FT218 exhibits predictable increases in plasma levels with increasing doses, consistent with the PK profile desired for a once-nightly sodium oxybate formulation. We are excited about the potential benefits of our once-nightly formulation and look forward to completion of the Phase 3 REST-ON trial, which is nearly two-thirds complete.”

Poster Presentations:

Poster 0609, presented Sunday, June 9, 5:15 – 7:15 p.m. CDT
“Pharmacokinetics and Formulation Selection of FT218, an Investigational Controlled-Release Sodium Oxybate Formulation Designed for Once-Nightly Dosing”

Poster 0610, presented Sunday, June 9, 5:15 – 7:15 p.m. CDT
“Pharmacokinetics and Dose Proportionality of FT218, an Investigational Controlled-Release Sodium Oxybate Formulation Designed for Once-Nightly Dosing”

The pharmacokinetics and formulation selection pilot study was designed as a four-way crossover study in 16 healthy volunteers, evaluating three proprietary once-nightly formulations of Micropump controlled-release sodium oxybate (FT218) versus twice-nightly immediate-release sodium oxybate at a nightly dose of 4.5g (two doses of 2.25g for immediate-release sodium oxybate). Each subject consumed a standard meal two hours prior to dosing. Subjects receiving the twice-nightly immediate-release sodium oxybate, were administered the second dose 4 hours after the first dose. Two subjects dropped out of the study prior to the completion. The key data for the 14 evaluable subjects demonstrates:

  • FT218 exhibited rapid initial absorption comparable to twice-nightly IR sodium oxybate
  • FT218 demonstrated a lower overall Cmax than twice-nightly IR sodium oxybate
  • FT218 mean blood concentrations (ug/ml) at 8 hours were similar to that of twice-nightly IR sodium oxybate
  • Safety and tolerability were similar across administrations

The dose proportionality study was an open-label, single-dose, three-sequential-period study in 20 healthy volunteers. Subjects received three separate single-dose 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. PK profiles were assessed for dose proportionality across the three doses and the results demonstrated:

  • FT218, at each dose, exhibited PK profiles consistent with those desired for once-nightly dosing
  • Dose proportionality was maintained for Cmax across the dosage range
  • Safety profile was consistent with what is known for sodium oxybate

The safety and efficacy of FT218 for the once-nightly treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy is currently being evaluated in the Phase 3, multi-centered, double-blind, placebo-controlled REST-ON trial, which is expected to complete enrollment in 2020. Poster reprints and REST-ON information will be available at Avadel’s Booth #1027 in the exhibit hall during the SLEEP 2019 conference.