Avadel Pharmaceuticals plc, a company focused on developing FT218, an investigational, once-nightly formulation of sodium oxybate designed to treat excessive daytime sleepiness and cataplexy in adults with narcolepsy, reports the online publication in journal Clinical Therapeutics of four Phase 1 studies from the FT218 pharmacokinetic program.
Due to its short half-life, conventional sodium oxybate treatment has required patients with narcolepsy to wake up in the middle of the night, two and a half to four hours after their first dose, to take their second dose to maintain therapeutic concentrations. Once-nightly FT218 utilizes Avadel’s proprietary, controlled-release technology platform to optimize the pharmacokinetic profile of sodium oxybate by providing a blend of immediate-release and controlled-release microparticles.
Key findings from the paper, titled “Pharmacokinetics of FT218, a Once-Nightly Sodium Oxybate Formulation in Healthy Adults,” include bioequivalent systemic drug exposure, as measured by area-under-the-curve, for the FT218 6 g dose compared to immediate-release sodium oxybate given as two, separate 3 g doses. What’s more, FT218 demonstrated a dose-proportional increase in Cmax and a slightly more than dose-proportional increase in area-under-the-curve. In all Phase 1 studies, FT218 exhibited a pharmacokinetic profile that supported once-nightly dosing with adequate concentrations maintained throughout the night, and gradual decline to lowest levels by 8-10 hours after dosing (that is, the time when most patients wake up in the morning).
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“These data should instill confidence in clinicians and patients regarding the robust Phase 1 development program for FT218, with the demonstration of predictable blood levels of the active ingredient with a single dose, and a low residual amount of active drug remaining when a patient would awaken,” says David Seiden, MD, lead author and senior medical director of clinical development and medical affairs at Avadel Pharmaceuticals, in a release. “As a sleep medicine physician and researcher, I am pleased that we have leveraged our proven technology to move toward the goal of patients potentially having access to a once-nightly sodium oxybate treatment.”
Results from these four Phase 1 studies have been previously presented at the 15th World Sleep Congress in Vancouver, Canada.
For all studies, adverse events with FT218 were mostly mild or moderate in severity, nonserious and known to be associated with sodium oxybate. Most common adverse events included somnolence, dizziness, and nausea.