Effectiveness and Safety of Low-Sodium Oxybate in Participants with Narcolepsy: Primary Results from the DUET Study

INTRODUCTION: A phase 4, prospective, open-label study of low-sodium oxybate (LXB) in narcolepsy (type 1 [NT1] or 2 [NT2]) or idiopathic hypersomnia included novel symptom outcomes important to patients (Jazz DUET; NCT05875974; registered 16 May 2023). Primary results from the narcolepsy cohort, including LXB effectiveness (nighttime sleep/daytime symptoms/overall disease severity) and safety are reported here. METHODS: DUET included screening, 8-day baseline (BL; off-LXB), 2-8-week LXB dose titration/optimization, 2-week stable-dose, 8-day end-of-treatment (EOT; on-LXB), and safety follow-up periods. At BL and EOT, participants underwent nocturnal polysomnography (PSG) and completed Epworth Sleepiness Scale (ESS; primary endpoint), Narcolepsy Severity Scale (NSS [NT1]; NSS-2 [NT2]), and Patient Global Impression of Severity (PGI-S) and Change (PGI-C); eDiaries for sleep quality and cataplexy (NT1 only) were completed daily for 8 days before PSGs. Least-squares mean (LSM) changes were adjusted for BL values. RESULTS: Thirty-four participants completed the study and were analyzed (NT1, n = 16; NT2, n = 18); LSM (SE) change in ESS score (BL to EOT), - 7.7 (0.9), P < 0.0001. At EOT versus BL, transitions to lighter stages of sleep decreased (LSM [SE] - 13.1 [2.9], P < 0.0001), N3 duration increased (45.0 [8.8] min, P < 0.0001), and nocturnal awakenings decreased (- 3.2 [0.9], P = 0.0013). LSM [SE] changes in NSS and NSS-2 scores were - 19.7 (2.7) and - 11.3 (1.6). Most participants reported improved sleep quality and overall narcolepsy disease and fewer cataplexy attacks. Treatment-emergent adverse events were consistent with the known LXB safety profile. CONCLUSION: DUET study results demonstrated novel nighttime sleep/daytime symptom improvements in participants with narcolepsy treated with open-label LXB. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05875974.