Cataplexy response with extended-release once-nightly sodium oxybate: Post hoc responder analyses from the phase 3 REST-ON clinical trial.

Background: Once-nightly sodium oxybate (ON-SXB), an extended-release oxybate formulation, yielded significant (P < 0.001 at 6 g, 7.5 g, and 9 g) reductions in cataplexy episodes in participants in the phase 3 REST-ON clinical trial (NCT02720744). This post hoc analysis from REST-ON further characterized changes in cataplexy episodes in participants with narcolepsy type 1 (NT1). Methods: Participants with narcolepsy aged ≥16 years received ON-SXB (1 wk, 4.5 g; 2 wk, 6 g; 5 wk, 7.5 g; 5 wk, 9 g) or placebo. Percentages of participants with NT1 who had ≥25%, ≥50%, ≥75%, and 100% reductions from baseline in mean number of weekly cataplexy episodes were determined. Two-sided P values comparing ON-SXB vs placebo were calculated with Fisher exact test. Results: Participants with NT1 (ON-SXB, n = 73; placebo, n = 72; modified intent-to-treat population) had a baseline mean number of weekly cataplexy episodes of 18.9 (ON-SXB) and 19.8 (placebo). Of participants receiving the highest doses of ON-SXB (7.5 and 9 g), approximately half had a 50% reduction, one-third had a 75% reduction, and one-tenth had a 100% reduction in their cataplexy episodes vs placebo. Significantly greater proportions of participants receiving ON-SXB vs placebo had respective reductions in weekly cataplexy episodes of ≥25% at weeks 1 (4.5 g; P < 0.05), 3 (6 g; P < 0.001), 8 (7.5 g; P < 0.001), and 13 (9 g; P = 0.001). Conclusions: A significantly greater proportion of participants receiving ON-SXB vs placebo experienced reductions in weekly cataplexy episodes at all tested doses. Approximately 10% of participants taking the 2 highest ON-SXB doses had complete elimination of their cataplexy.

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.