Effectiveness and Safety of Low-Sodium Oxybate in Participants With Narcolepsy or Idiopathic Hypersomnia: Top-line Results From the Phase 4 DUET Study
Logan Schneider1, David Plante2, Deborah A. Nichols3, Teresa Steininger3, Douglas S. Fuller3, M. Todd Kirby4, Sarah Akerman3, Jessica Alexander3, Chad Ruoff5, Alyssa Cairns6
1Stanford University Center for Sleep Sciences and Medicine, 2Department of Psychiatry, University of Wisconsin–Madison, 3Jazz Pharmaceuticals, 4Jazz Pharmaceuticals, Medical College of Georgia at Augusta University, 5Mayo Clinic, 6BioSerenity, Inc.
Objective:
To evaluate effectiveness and safety of low-sodium oxybate (LXB; Xywav®) on excessive daytime sleepiness (EDS) in narcolepsy or idiopathic hypersomnia (IH), sleep architecture and sleep disruption based on polysomnography (narcolepsy cohort) and additional symptoms (IH cohort).
Background:
Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, open-label, multiple-cohort study (NCT05875974).
Design/Methods:
DUET comprised a screening period (including 2-week washout for current oxybate users), 8-day baseline (BL) period, 2- to 8-week LXB titration period, 2-week stable-dose period, 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. Key secondary endpoints included, for narcolepsy, change in total sleep stage shifts (deeper to lighter), N3 sleep duration, and number of awakenings, and, for IH, change in Idiopathic Hypersomnia Severity Scale (IHSS) score.
Results:
Most dosed participants (narcolepsy, N=55; IH, N=46) were female (72.7%; 80.0%) and White (80.0%; 85.0%), respectively. For narcolepsy, least-squares mean (LSM) (SE) changes from BL to EOT for ESS, total shifts from deeper to lighter stages of sleep, N3 sleep duration (minutes), and number of awakenings were −7.7 (0.9), P<0.0001; −13.1 (3.0), P<0.0001; 45.0 (8.8), P<0.0001; and −3.2 (0.9), P=0.0015 (n=34 each), respectively. For IH, LSM (SE) changes in ESS and IHSS were −8.4 (0.7), P<0.0001 (n=40) and −15.5 (1.5), P<0.0001 (n=36), respectively. Treatment-emergent adverse events (TEAEs) were mild or moderate in severity; the three most common TEAEs were nausea, dizziness, and headache. One serious hypoxia event (concurrent with influenza) unrelated to study drug, which resolved, occurred in the IH cohort.
Conclusions:
Participants with narcolepsy or IH taking open-label LXB showed improvements in ESS scores, reduced sleep stage shifts, increased deep sleep (N3), and reduced number of awakenings (narcolepsy) and improvements in ESS and IHSS scores (IH).
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