Design Elements for a Switch Study From High- to Low-Sodium Oxybate Evaluating Blood Pressure in Narcolepsy (XYLO)

Introduction: High sodium intake can increase blood pressure (BP) and cardiovascular risk. Individuals with narcolepsy have elevated cardiovascular comorbidity burden before considering medication-specific risks. Low-sodium oxybate (LXB; Xywav®) is US FDA-approved to treat excessive daytime sleepiness or cataplexy in patients aged ≥7 years with narcolepsy. LXB has the same active moiety as the high-sodium oxybate known as sodium oxybate (SXB, Xyrem®), but contains 92% less sodium. The objective of XYLO is to measure ambulatory and in-clinic systolic BP (SBP) changes after switching to LXB from twice-nightly SXB in participants with narcolepsy (NCT05869773).

Methods: This 6-week, open-label, multicenter, decentralized, switch study enrolls participants aged 18–70 years with narcolepsy (type 1 or 2) taking 6–9 g/night of twice-nightly SXB for ≥6 weeks. After ≥2 weeks on stable twice-nightly SXB, participants switch to same dose/regimen of LXB for 6 weeks. The primary endpoint is the change from baseline to end-of-treatment visit in 24-hour ambulatory SBP. Secondary endpoints are change from baseline to end-of-treatment visit for in-clinic SBP and daytime and nighttime average SBP assessed by ambulatory BP monitoring.

Results: Recruitment began in June 2023. This study uses a group sequential design with an adaptive sample size target of 57–77 participants completing the 6-week intervention period, providing 90% power to detect a mean difference of 3.5 mmHg in 24-hour SBP.

Conclusion: Results from XYLO will inform on BP following transition to LXB from twice-nightly SXB. Hybrid enrollment with a decentralized option may increase study access for a more diverse trial population.