(32) Impact of switching from high- to low-sodium oxybate on ambulatory blood pressure in people with narcolepsy

Background: : People with narcolepsy (PwN) have an increased incidence of hypertension and cardiovascular disease (CVD) risk. Excess sodium intake is strongly associated with hypertension and CVD.

Objective: : To evaluate the impact of switching from twice-nightly high-sodium oxybate (SXB; Xyrem®) to low-sodium oxybate (LXB; Xywav®) on ambulatory and seated resting (“office”) blood pressure (BP) in PwN.

Methods: : XYLO, an open-label, single-arm study (NCT05869773), evaluated PwN aged 18−70 years with screening systolic blood pressure (SBP) 130−155 mmHg taking twice-nightly SXB 6–9 g for ≥6 wks, switching to LXB (same dosage/regimen) for ≈6 wks. The primary endpoint was change in mean 24-hour ambulatory SBP from baseline (BL) to end-of-treatment (EOT). Secondary endpoints were changes in mean daytime ambulatory, office, and nighttime ambulatory SBP. Exploratory endpoints included changes in mean 24-hour ambulatory, daytime ambulatory, office, and nighttime ambulatory diastolic BP (DBP). An interim analysis using prespecified stopping criteria (75% completers) was performed. One-sided P-values (“*” for statistical significance) for SBP least squares mean (LSM) changes (95% CI) and two-sided nominal P-values for DBP changes, are reported. Changes are BL-adjusted.

Results: : Mean (SD) baseline office SBP and DBP were 138.0 (5.7) and 85.2 (6.6) mmHg, respectively, for 43 PwN (mean age, 45 y; 65% female; stable antihypertensive use, 33%). Mean (SD) total SXB and LXB dosage was 8.0 (1.1) and 8.1 (1.1) g/night, respectively, representing 1456.5 (206.2) and 117.8 (16.3) mg sodium (mean [SD] difference: 1338.8 [190.7] mg sodium); median 24-hour urinary sodium was 4232.0 mg/d at BL and 2702.5 mg/d at EOT. Mean (SD) 24-hour BL and EOT SBPs were 132.3 (11.6) and 128.2 (12.0) mmHg, respectively; change was −4.1 (−6.9, −1.4; P=0.0019*) mmHg, meeting prespecified study stopping criteria. Mean daytime and nighttime ambulatory SBP changes were −5.1 (−7.8, −2.4; P=0.0003*) and −2.0 (−5.3, 1.4; P=0.1265) mmHg, respectively; mean office SBP change was −9.2 (−11.9, −6.5; P< 0.0001*). Change in mean 24-hour DBP was −2.3 (−4.1, −0.5; P=0.0118); mean daytime and nighttime ambulatory DBP changes were −2.8 (−4.8, −0.9; P=0.0045) and −1.1 (−3.6, 1.5; P=0.3993); mean office DBP change was −3.8 (−6.0, −1.6; P=0.0014). Treatment-emergent adverse events (all mild/moderate) occurred in 33% of participants.

Conclusions: : Switching from SXB to LXB reduced daily medication-related sodium intake in PwN and was associated with clinically meaningful BP reductions, consistent with evidence on sodium reduction effects.

Sponsorship:: Jazz Pharmaceuticals