Macfadden, Wayne

Abstract Introduction High sodium intake can increase blood pressure (BP) and future cardiovascular risk. Individuals with narcolepsy have an elevated cardiovascular comorbidity burden before considering medication-specific risks. Low-sodium oxybate (LXB; Xywav®) is approved by the US Food and Drug Administration (FDA) to treat excessive daytime sleepiness or cataplexy in patients ≥7 years of age with narcolepsy and idiopathic hypersomnia in adults. LXB has the same active moiety as high-sodium oxybates (sodium oxybate [SXB, Xyrem®] and fixed-dose SXB [Lumryz™]) 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 a high-sodium oxybate in participants with narcolepsy (NCT05869773). Methods This 6-week, open-label, multicenter, switch study is enrolling participants 18–70 years of age with narcolepsy (type 1 or 2) taking 6–9 g/night of high-sodium oxybate for ≥6 weeks. Hybrid enrollment supports both on-site and decentralized (monitored at the participant’s home by mobile health professionals) participation, and may broaden the pool of eligible participants. After ≥2 weeks on stable high-sodium oxybate dose/regimens (screening period), participants switch to the same dose/regimen of LXB for 6 weeks (intervention period). The primary endpoint is the change in 24-hour SBP from baseline (the most recent screening measurement prior to switching) to the end-of-treatment visit (approximately 6 weeks after switching) measured via 24-hour ambulatory BP monitoring (ABPM). Secondary endpoints evaluate change from baseline to end-of-treatment visit in-clinic SBP, as well as daytime average SBP and nighttime average SBP measured via 24-hour ABPM. 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. This design provides 90% power to detect a mean difference of 3.5 mmHg (a clinically relevant change) in 24-hour SBP (assuming a standard deviation of the differences in 24-hour SBP of 8 mmHg). Conclusion XYLO will enable the assessment of 24-hour BP changes following transition from a high-sodium oxybate to LXB. Planned hybrid enrollment with a decentralized option may increase study access leading to a more diverse clinical trial population. Support (if any) Jazz Pharmaceuticals