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

• Published in: Sleep (New York, N.Y.) Vol. 45; no. 6; p. 1
• Main Authors: Kushida, Clete A, Shapiro, Colin M, Roth, Thomas, Thorpy, Michael J, Corser, Bruce C, Ajayi, Akinyemi O, Rosenberg, Russell, Roy, Asim, Seiden, David, Dubow, Jordan, Dauvilliers, Yves
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 13.06.2022
• Subjects: Armodafinil; Cataplexy - drug therapy; Chronic illnesses; Clinical trials; Complications and side effects; Disease; Double-Blind Method; Drug dosages; Editor's Choice; Gamma-hydroxybutyrate; Hospitalization; Humans; Life Sciences; Narcolepsy; Narcolepsy - drug therapy; Neurological Disorders; Neurology; Neurons and Cognition; Patient compliance; Patients; Pharmaceutical sciences; Pharmacokinetics; Pharmacology; Sleep disorders; Sleepiness; Sodium; Sodium Oxybate - adverse effects; Treatment Outcome; Type 2 diabetes; Wakefulness; France; sodium oxybate; once-nightly; narcolepsy; safety; NT1/NT2; modified release; Once-nightly; Narcolepsy; Safety; Modified release; Sodium oxybate
• ISSN: 0161-8105; 1550-9109
• DOI: 10.1093/sleep/zsab200

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.