Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy

Clete A Kushida; Colin M Shapiro; Thomas Roth; Michael J Thorpy; Bruce C Corser; Akinyemi O Ajayi; Russell Rosenberg; Asim Roy; David Seiden; Jordan Dubow; Yves Dauvilliers

doi:10.1093/sleep/zsab200

Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy

Sleep. 2022 Jun 13;45(6):zsab200. doi: 10.1093/sleep/zsab200.

Authors

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Redwood City, CA, USA.
² University of Toronto, Toronto, ON, Canada.
³ Sleep Disorders and Research Center, Henry Ford Health System, Detroit, MI, USA.
⁴ Department of Neurology, Montefiore Medical Center, New York, NY, USA.
⁵ Sleep Management Institute, Cincinnati, OH, USA.
⁶ Florida Pediatric Research Institute, Winter Park, FL, USA.
⁷ Neurotrials Research, Inc., Atlanta, GA, USA.
⁸ Ohio Sleep Medicine and Neuroscience Institute, Dublin, OH, USA.
⁹ Avadel Pharmaceuticals, Chesterfield, MO, USA.
¹⁰ National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia, Sleep Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, Univ Montpellier, INM INSERM, Montpellier, France.

Abstract

Study objectives: To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial.

Methods: Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness Test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments.

Results: In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n = 107) or placebo (n = 105). For the three coprimary endpoints and Epworth Sleepiness Scale, all three doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement versus placebo (all p < 0.001). For ON-SXB 9 g versus placebo, increase in mean sleep latency was 10.8 versus 4.7 min (Least squares mean difference, LSMD [95% CI], 6.13 [3.52 to 8.75]), 72.0% versus 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76 to 11.23]), change in mean weekly number of cataplexy attacks was -11.5 versus -4.9 (LSMD [95% CI], -6.65 [-9.32 to -3.98]), and change in Epworth Sleepiness Scale was -6.5 and -2.7 (LSMD [95% CI], -6.52 [-5.47 to -2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis.

Conclusions: ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose.

Clinical trial registration: ClinicalTrials.gov: NCT02720744, https://clinicaltrials.gov/ct2/show/NCT02720744.

Keywords: NT1/NT2; modified release; narcolepsy; once-nightly; safety; sodium oxybate.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Cataplexy* / drug therapy
Double-Blind Method
Humans
Narcolepsy* / drug therapy
Sleepiness
Sodium Oxybate* / adverse effects
Treatment Outcome
Wakefulness

Substances

Sodium Oxybate

Associated data

ClinicalTrials.gov/NCT02720744