Effectiveness and Safety of Low-Sodium Oxybate in Participants With Idiopathic Hypersomnia: Top-line Results From the Phase 4 DUET Study
Introduction: Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, open-label study (NCT05875974) evaluating the effectiveness of low-sodium oxybate (LXB, Xywav®) treatment on excessive daytime sleepiness (EDS), polysomnography, and functional outcomes in participants with idiopathic hypersomnia (IH) or narcolepsy.
Methods: DUET comprised a screening period (2-week washout for current oxybate users), 8-day baseline (BL) period, 2- to 8-week LXB titration period, 2-week stable-dose period (SDP), 1- to 2-week end-of-treatment period (EOT), and 2-week safety follow-up. The primary endpoint was the change in Epworth Sleepiness Scale (ESS) score; additional endpoints included Idiopathic Hypersomnia Severity Scale (IHSS) and Patient Global Impression of Change (PGIc) for overall symptoms and sleep inertia.
Results: Forty-six IH participants enrolled. Most were female (80%) and White (85%). Mean (SD) age was 38.1 (11.8) years. At study entry, 9/46 participants were taking LXB before washout. Mean (SD) total nightly LXB dose during SDP (Nf41) was 6.6 (1.8) grams. BL mean (SD) ESS and IHSS scores were 16.5 (2.7) and 32.9 (7.1), respectively. Least-squares mean (SE) changes in ESS (Nf40) and IHSS (Nf36) from BL to EOT were −8.4 (0.7), P < 0.0001 and −15.5 (1.5), P < 0.0001, respectively. Most participants reported improvement (very much, much, minimally) on the PGIc–overall (94.6%; Nf37) and PGIc–sleep inertia (81.1%; Nf37). Treatment-emergent adverse events (TEAEs) were mild or moderate; common TEAEs were nausea, dizziness, and headache.
Conclusions: Participants with IH taking open-label LXB showed improvements in symptoms, including EDS and sleep inertia.
