SESSION TITLE: Cataplexy-Free Days in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of Lower-Sodium Oxybate in Adults With Narcolepsy With Cataplexy
PRESENTING AUTHOR: Dauvilliers, Yves1,2
CO-AUTHORS: Foldvary-Schaefer, Nancy3 ; Bogan, Richard K.4 ; Šonka, Karel5 ; Thorpy, Michael J.6
AFFILIATIONS: 1 Sleep and Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital, Montpellier, France; 2 University of Montpellier, INM INSERM, Montpellier, France; 3 Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA; 4 University of South Carolina School of Medicine, Columbia, SC, USA; 5 First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 6 Albert Einstein College of Medicine, Bronx, NY, USA
Introduction: Sodium oxybate (SXB; Xyrem®) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. Lower-sodium oxybate (LXB; Xywav™; formerly designated JZP-258) is an oxybate medication with 92% less sodium than SXB. The US Food and Drug Administration approved LXB in July 2020 for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy.
Objective: This analysis evaluated cataplexy-free days/week, as a measure of treatment impact, in a placebo-controlled randomized withdrawal study of LXB treatment in participants with narcolepsy.
Methods: Treatment for cataplexy at study entry included 1) SXB (SXB-only); 2) SXB plus other anticataplectics (SXB+other); 3) anticataplectics other than SXB (other anticataplectics); or 4) cataplexy treatment-naive (anticataplectic-naive). Participants (aged 18–70 years with narcolepsy with cataplexy) began LXB treatment during a 12-week, open-label, optimized treatment and titration period (OLOTTP), followed by a 2-week stable-dose period (SDP). Participants were then randomized to receive placebo or continue LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP).
Results: Of 201 enrolled participants, 134 comprised the efficacy population (placebo, n=65; LXB, n=69). Median (1st quartile [Q1], 3rd quartile [Q3]) cataplexy-free days/week at first week of OLOTTP (while initiating LXB) by prior treatment were higher in participants entering taking SXB: SXB-only (n=41), 5.8 (2.0, 7.0); SXB+other (n=14), 6.4 (5.0, 7.0); other anticataplectics (n=21), 4.0 (1.8, 6.0); anticataplectic-naive (n=57), 3.5 (0, 5.8). At end of SDP (on stable dose of LXB), median (Q1, Q3) cataplexy-free days/week were similar in all treatment groups (6.0 [3.5, 7.0], 6.1 [1.4, 7.0], 6.0 [2.6, 7.0], and 6.2 [4.0, 7.0], respectively). Prior to randomization, there was no difference in median cataplexy-free days/week between participants to be randomized to placebo (6.0 [3.5, 7.0]) or LXB treatment (6.0 [3.0, 7.0]); during DBRWP, median cataplexy-free days/week decreased in participants randomized to placebo (3.5 [0, 5.8]) but remained similar in participants randomized to continue LXB treatment (5.6 [2.8, 7.0]). Common (≥10%) treatment-emergent adverse events were headache, nausea, and dizziness.
Conclusion: Number of cataplexy-free days/week increased with LXB treatment in participants previously naive to oxybate. Number of cataplexy-free days/week decreased during placebo exposure in participants randomized to placebo. The overall safety profile of LXB was similar to that of SXB.
PS2:S201 - Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of Lower-Sodium Oxybate in Adults With Idiopathic Hypersomnia
PRESENTING AUTHOR: Foldvary-Schaefer, Nancy 4 CO-AUTHORS : Arnulf, Isabelle 3 ; Chandler, Patricia 5 ; Parvataneni, Rupa 5 ;.. →