Safety of Low-Sodium Oxybate in Participants With Narcolepsy or Idiopathic Hypersomnia, With of Without Comorbid Obstructive Sleep Apnea: A Post Hoc Analysis of the Duet Study

Document Type

Conference Proceeding

Publication Date

5-2026

Publication Title

American Journal of Respiratory and Critical Care Medicine

Abstract

Rationale: Low-sodium oxybate (LXB; Xywav®) is FDA approved for treatment of cataplexy and excessive daytime sleepiness (EDS) in people ≥7 years of age with narcolepsy, and for idiopathic hypersomnia in adults. LXB Prescribing Information includes a Warning and Precaution for respiratory depression and sleep-disordered breathing; therefore, data on safety of LXB in people with obstructive sleep apnea (OSA; a common comorbidity among people with narcolepsy or idiopathic hypersomnia) are needed. This post hoc analysis of DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974), a prospective, open-label phase 4 study, evaluated respiratory parameters in participants taking LXB with or without comorbid OSA, in 3 cohorts: narcolepsy or idiopathic hypersomnia (LXB ≤9 g/night), or narcolepsy (LXB >9 g/night). Methods: Participants underwent the following study periods: screening, 8-day baseline (BL; off-LXB for narcolepsy and idiopathic hypersomnia cohorts; on-LXB 9 g/night for >9 g cohort), 2-8-week dose titration, 2-week stable-dose, 8-day end-of-treatment (EOT; on optimized total nightly dosage; ≤12 g for the >9 g cohort), and 2-week safety follow-up. Participants with BL apnea-hypopnea index (AHI) >10 (treated/untreated OSA) were excluded from the study. Overnight polysomnography assessments conducted at BL and EOT included respiratory parameters: AHI, central apnea index (CAI), and percentage of total sleep time spent with oxygen saturation (SpO2) < 90% (T90). Treatment-emergent adverse events (TEAEs) were assessed by OSA group. Least squares mean changes were adjusted for BL values. Results: Fifty-five participants enrolled in the narcolepsy cohort, 9% (5/55) had comorbid OSA; 22% (10/46) and 31% (15/48) had comorbid OSA in the idiopathic hypersomnia and narcolepsy >9 g cohorts, respectively (3, 9, and 12 were on OSA treatment throughout the study). Most participants (narcolepsy, idiopathic hypersomnia, narcolepsy >9 g) were female (72.7%, 80.4%, 62.5%) and White (80.0%, 84.8%, 77.1%). No worsening of sleep-disordered breathing was observed during LXB treatment, as evidenced by respiratory parameters AHI, CAI, and T90 assessed at BL and EOT in either participants with or without OSA (Table 1). Percentages of participants with/without OSA reporting ≥1 TEAE were 60.0%/62.0% (narcolepsy), 80.0%/72.2% (idiopathic hypersomnia), and 66.7%/78.8% (narcolepsy >9 g). Most TEAEs were mild or moderate; 1 serious TEAE each occurred in the idiopathic hypersomnia cohort (with OSA) and the narcolepsy >9 g cohort (without OSA). Conclusions: No worsening respiratory signals were observed with LXB treatment in participants with or without comorbid (mild or treated) OSA in the narcolepsy, idiopathic hypersomnia, or narcolepsy taking >9 g LXB dosage cohorts.

Volume

212

Issue

S1

First Page

S4772

Last Page

S4772

Comments

American Thoracic Society International Conference, May 15-20, 2026, Orlando, FL

DOI

10.1093/ajrccm/aamag162.6396

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