Cataplexy-Free Days With Sodium Oxybate Treatment in Children/Adolescents With Narcolepsy With Cataplexy (1211)

Objective: To determine the number of cataplexy-free days/week experienced by participants treated with sodium oxybate (SXB) in a placebo-controlled, randomized withdrawal study in children and adolescents with narcolepsy with cataplexy.

Background: Cataplexy resolves in some patients with narcolepsy when treated with SXB.

Design/Methods: SXB-naive participants were titrated to an optimal dose of SXB and then entered a stable-dose period (SD) for 2 weeks; participants already taking SXB entered SD on their usual dose of SXB for 3 weeks. After a 2-week, placebo-controlled, double-blind, randomized withdrawal period (DB), participants entered an open-label safety period (OL) for a total duration of ≤1 year. Cataplexy-free days/week were calculated from daily participant diaries.

Results: Of 106 participants, 74 (69.8%) were SXB naive and 32 (30.2%) were taking SXB at enrollment. In SXB-naive participants, median (Q1, Q3) cataplexy-free days/week increased during titration: week 1 (0.0 [0.0, 2.0]), week 2 (1.0 [0.0, 3.0]), and last 7 days (4.0 [1.0, 6.0]); n=71. Sixty-seven SXB-naive participants entered SD. During the last 14 days of SD, cataplexy-free days/week remained stable and were similar in participants who were SXB naive or taking SXB at study entry: 4.3 (1.0, 5.8), n=66, and 4.8 (0.8, 6.5); n=32, respectively. During the last week of DB, cataplexy-free days/week decreased to 0.0 (0.0, 2.7) in participants randomized to placebo (n=32) but remained stable at 4.0 (1.0, 6.0) in participants continuing SXB (n=31). During the last week of observation for each participant in the OL period, median cataplexy-free days/week was 5.0, in both participants who were SXB naive (n=63) and participants taking SXB at study entry (n=32). Common adverse events (>10%) in the safety population (n=104) were enuresis, nausea, vomiting, headache, and decreased weight.

Conclusions: SXB treatment increased cataplexy-free days/week in children/adolescents with narcolepsy with cataplexy. The safety profile was consistent with previous adult and pediatric narcolepsy studies.

Disclosure: Dr. Mignot has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr Mignot has consulted for Novo Nordisk and Reset Pharmaceuticals, and is on the speakers' bureau for Vox Media.. Dr. Mignot has received research support from Dr. Mignot has received research support from Jazz Pharmaceuticals, Merck, and Glaxo Smith Kline (GSK). Dr. Rosen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Rosen has been a consultant for Jazz Pharmaceuticals, Advance-Medical and Natus Medical.. Dr. Rosen has received research support from Has received research funding from Jazz Pharmaceuticals and Flamel Technologies and acknowledges the following support: “In Cleveland, this publication was made possible by the Clinical and Translational Science Collaborative of Cleveland, 4UL1TR000439 fr. Dr. Menno has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Menno has received compensation for serving on the Board of Directors of Full-time employee of Jazz Pharmaceuticals who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals, plc.. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Wang has received compensation for serving on the Board of Directors of Full-time employee of Jazz Pharmaceuticals who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals, plc.. Dr. Profant has received compensation for serving on the Board of Directors of Full-time employee of Jazz Pharmaceuticals who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals, plc.. Dr. Dauvilliers has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bioprojet, Flamel Technologies S.A. (now Avadel Pharmaceuticals plc), Harmony Biosciences, LLC, Idorsia Pharmaceuticals Ltd., Jazz Pharmaceuticals, Takeda Pharmaceutical Co. Ltd., Theranexus, and UCB Pharma.