Randomized, crossover, open-label study of the relative bioavailability and safety of FT218, a once-nightly sodium oxybate formulation: Phase 1 study in healthy volunteers

Richard Bogan, Michael J. Thorpy, John W. Winkelman, Jordan Dubow, Jennifer Gudeman, David Seiden

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Treatment for narcolepsy with sodium oxybate (SXB) has required twice-nightly dosing, at bedtime and 2.5–4 h later. This study evaluated the pharmacokinetics of FT218, an investigational, extended-release, once-nightly formulation of SXB (ON-SXB), vs twice-nightly SXB. Methods: In this phase 1, open-label study, healthy volunteers were randomized (1:1) to ON-SXB 6 g or twice-nightly SXB (two 3-g doses administered 4 h apart); minimum 3-day washout before crossover. Doses were administered 2 h post-evening meal. Blood samples for pharmacokinetic assessments were collected predose and up to 14 h after the first dose during each treatment period. Results: Twenty-eight participants were enrolled (mean age, 39.6 years; 54% women; 93% white). Mean ± SEM area under the concentration-time curve for ON-SXB was 282.7 ± 30.2 μg·h/mL vs 273.3 ± 27.8 μg·h/mL for twice-nightly SXB. Geometric mean ratio (GMR; 90% CI) was 102.9 (98.0–108.0). Maximum γ-hydroxybutyrate (GHB) plasma concentration (Cmax) was 65.8 ± 4.0 μg/mL for ON-SXB vs 77.1 ± 4.9 μg/mL for twice-nightly SXB (GMR [90% CI], 88.3 [80.5–97.0]). The GMR (90% CI) for GHB plasma concentrations 8 h post dose (C8h) for ON-SXB vs twice-nightly SXB was 61.7 (45.8–83.0). The most frequently reported adverse events were the same for ON-SXB and twice-nightly SXB (nausea, dizziness, somnolence, vomiting). Conclusions: GHB exposure and Cmax with one 6-g dose of ON-SXB were bioequivalent to those with two 3-g doses of twice-nightly SXB, whereas C8h was lower with ON-SXB. If approved, ON-SXB will provide a single bedtime oxybate option, with clinically relevant pharmacologic exposure during the entire sleep period.

Original languageEnglish (US)
Pages (from-to)442-447
Number of pages6
JournalSleep Medicine
Volume100
DOIs
StatePublished - Dec 2022

Keywords

  • Narcolepsy
  • Once-nightly
  • Pharmacokinetics
  • Sodium oxybate

ASJC Scopus subject areas

  • Medicine(all)

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