Lower-Sodium Oxybate Dose Titration and Transition From Sodium Oxybate in a Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adult Participants With Narcolepsy With Cataplexy (2163)

Objective: Evaluate dose adjustment of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate, LXB; Xywav™; previously designated as JZP-258) during titration in a double-blind, placebo-controlled, randomized withdrawal study. Background: Sodium oxybate (SXB; Xyrem®) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. LXB is an oxybate medication with 92% less sodium than SXB. Design/Methods: At study entry, participants were taking SXB only, SXB+other anticataplectics, anticataplectics other than SXB, or were cataplexy treatment–naive. LXB treatment began during a 12-week, open-label optimized treatment and titration period. Participants taking SXB only or SXB+other anticataplectics transitioned to LXB at the same gram-for-gram dose as SXB and adjusted to an efficacious and tolerable (optimized) dose during weeks 3–12. Participants taking other anticataplectics or who were anticataplectic-naive initiated LXB at 4.5 g/night and titrated to an optimized dose at ≤1.5 g/night/week (maximum total dose, 9 g/night). A 2-week stable-dose period (SDP) and 2-week, double-blind, randomized withdrawal period followed. Results: Most participants (91%) taking SXB at study entry had no dose adjustment or adjustments within 1 titration step (±1.5 g/night). The median (range) number of adjustments was 0.0 (0–8) in participants taking SXB at study entry and 3.0 (0–7) in participants not taking SXB at study entry. Total nightly stable LXB dose (median [range]) was higher in participants taking SXB at study entry (SXB-only, 7.5 g [4.5–9.0], n=41; SXB+other anticataplectics, 9.0 g [6.0–9.0], n=14) compared with those not taking SXB (other anticataplectics, 7.5 g [4.5–9.0], n=21; anticataplectic-naive, 7.0 g [3.0–9.0], n=58), with fewer dose adjustments made. Conclusions: Most participants taking SXB at study entry transitioned to LXB at the same dose or within 1 titration step. Participants not previously taking SXB achieved an individually optimized dose of LXB after a median of 3 adjustments. Disclosure: Dr. Foldvary-Schaefer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz. The institution of Dr. Foldvary-Schaefer has received research support from Jazz. The institution of Dr. Foldvary-Schaefer has received research support from Suven. The institution of Dr. Foldvary-Schaefer has received research support from Takeda. Dr. Foldvary-Schaefer has received publishing royalties from a publication relating to health care. Dr. Foldvary-Schaefer has received publishing royalties from a publication relating to health care. Richard K. Bogan, MD has nothing to disclose. Dr. Thorpy has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Jazz. Lin Huang has received personal compensation for serving as an employee of Jazz pharmaceuticals. Dr. Skowronski has nothing to disclose. Yves Dauvilliers has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for idorsia. Yves Dauvilliers has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for JAZZ. Yves Dauvilliers has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda.