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

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.