Quality of Life in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of Lower-Sodium Oxybate in Adults With Narcolepsy With Cataplexy (2044)

Objective: Establish the efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate, LXB; Xywav™; previously designated as JZP-258) in a double-blind randomized withdrawal study in adults with narcolepsy with cataplexy. Health-related quality of life (HRQoL) endpoints from this study are presented. Background: Narcolepsy negatively impacts HRQoL. Sodium oxybate (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. Design/Methods: Participants 18–70 years of age began LXB treatment during a 12-week, open-label, optimized treatment and titration period, followed by a 2-week stable-dose period. Participants were then randomized to receive placebo or continue LXB treatment during a 2-week, double-blind, randomized withdrawal period. HRQoL assessments included the 36-Item Short Form Health Survey Version 2 (SF-36) and 5-level EuroQoL 5-Dimensions Self-Report Questionnaire (EQ-5D-5L). Results: 201 participants enrolled; 134 were randomized and received at least 1 dose of double-blind study medication (efficacy population; placebo, n=65; LXB, n=69). Decreased scores (worsening) were observed in participants randomized to placebo compared with participants randomized to continue LXB treatment for the SF-36 physical component summary (median [Q1, Q3], −1.92 [−3.46, 1.73] for placebo and −0.03 [−2.07, 2.41] for LXB; nominal P=0.02), SF-36 mental component summary (−1.92 [−6.28, 1.34] for placebo and 1.55 [−1.88, 3.78] for LXB; nominal P=0.03), and EQ-5D-5L visual analog scale (−5.0 [−10.0, 5.0] for placebo and 0.0 [0.0, 5.0] for LXB; nominal P=0.0056). No change was observed in the EQ-5D-5L crosswalk index (0.00 [−0.05, 0.03] for placebo and 0.00 [−0.01, 0.03] for LXB; nominal P=0.3918). The overall safety profile of LXB was similar to sodium oxybate. Conclusions: HRQoL worsened in those randomized to placebo during the 2-week double-blind randomized withdrawal period but remained stable in participants who continued LXB treatment. 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. Dr. Thorpy has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant 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 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. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharma. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Harmony biosciences. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eisai . Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Inspire. The institution of Dr. Roy has received research support from Jazz . The institution of Dr. Roy has received research support from Inspire. The institution of Dr. Roy has received research support from Avadel. Lihua Tang has nothing to disclose. Dr. Skowronski has nothing to disclose. Karel Sonka has received personal compensation for serving as an employee of Jazz. Karel Sonka has received personal compensation for serving as an employee of Flamel-Avadel. Karel Sonka has received personal compensation for serving as an employee of Luitpold Pharmaceutical. Karel Sonka has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Karel Sonka has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Karel Sonka has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Angelini. Karel Sonka has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Stada. Karel Sonka has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Richard K. Bogan, MD has nothing to disclose.