Effectiveness and Safety of Low-Sodium Oxybate in Participants With Narcolepsy: 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®) on excessive daytime sleepiness (EDS) and polysomnography (PSG)–based sleep structure and disruption in participants with narcolepsy or idiopathic hypersomnia.
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 change in Epworth Sleepiness Scale (ESS) score from BL to EOT. Narcolepsy cohort key secondary endpoints included 3 PSG parameters.
Results: Fifty-five narcolepsy participants enrolled. Most were female (73%) and White (80%). Mean (SD) age was 33.4 (12.9) years. Thirteen participants were taking oxybate at study entry before washout. During SDP (Nf36), the mean (SD) total nightly LXB dose was 7.0 (1.6) grams. BL mean (SD) ESS score was 16.3 (3.1); least-squares mean (LSM) (SE) change from BL to EOT was −7.7 (0.9), P < 0.0001 (Nf34). LSM (SE) changes for total shifts from deeper to lighter stages of sleep, N3 sleep duration (minutes), and number of awakenings were −13.1 (3.0), P < 0.0001; 45.0 (8.8), P < 0.0001; and −3.2 (0.9), P=0.0015, respectively (Nf34 each). Treatment-emergent adverse events (TEAEs) were mild or moderate in severity; common TEAEs included nausea, dizziness and headache.
Conclusions: Participants with narcolepsy taking open-label LXB showed improvements in EDS, sleep stage shifts, deep sleep (N3), and awakenings.
