Résumé
Introduction Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder characterized by excessive daytime sleepiness, prolonged nighttime sleep and sleep inertia. The efficacy and safety of low-sodium oxybate was reported in a phase 3 randomized withdrawal study in IH on Epworth Sleepiness scale (ESS) and Idiopathic Hypersomnia Severity Scale (IHSS). We conducted a phase 3, monocentric, double-blind, randomized, parallel group, placebo-controlled trial of sodium oxybate (SXB) in IH with ESS, IHSS and Maintenance of Wakefulness Test (MWT) assessment. Methods Eligible participants 18–60 years of age with IH according to criteria (ICSD3) with ESS ≥14 were randomly assigned to treatment with SXB or placebo in a 1:1 ratio. After a 2-week screening without any CNS drugs and never exposed to oxybate, patients started a 6-week individual twice nightly up-titration scheme from 4.5 g to a maximum of 9 g, treatment was administered at stable dose (6g or 9g) for 2 weeks, followed by a 1-week taper period. The primary endpoint was the mean change from baseline to week 8 on ESS. Key secondary endpoints were safety, changes in average sleep latency on the MWT and IHSS. Results Between October 2018 and January 2023, we screened 48 patients, 45 were randomized (36 females, mean age 29.0±7.5, ESS 16.5±2.7, 40 having long sleep time; 22 assigned to SXB and 23 placebo), and 40 (19 receiving SXB and 21 placebo) completed the double-blind period. Between-group differences (SXB vs placebo) for the mean [IC95%] change in ESS from baseline to endpoint were -6.54 [-9.35;-3.73] (p=0.004). Between-group differences for the average sleep latency on the MWT from baseline to endpoint were 13.87 [8.35 ;19.39] (p=0.0001), and for IHSS -10.87 [-15.71;-6.03] (p=0.0004). Treatment-emergent adverse events were reported in 17 (77%) of 22 patients with SXB and 7 (30%) of 23 with placebo. The most frequently reported adverse events were nausea, headache, and dizziness. Conclusion SXB resulted in a clinically meaningful improvement in adults with IH, reducing excessive sleepiness on the ESS, improving wakefulness on the MWT and decreasing IH severity on IHSS after 8 weeks. The safety profile was similar to that previously reported with SXB. NCT03597555 Support (if any) Grant from Jazz Pharmaceuticals