Sodium Oxybate Treatment Effects on Sleep Architecture in Pediatric Patients With Narcolepsy With Cataplexy (1172)

Objective: Evaluate sodium oxybate (SXB) effects on sleep architecture in pediatric narcolepsy. Background: SXB is approved for cataplexy and excessive daytime sleepiness in patients with narcolepsy. A placebo-controlled, double-blind, randomized-withdrawal study established efficacy and safety of SXB in pediatric patients (7–17 years of age) (Part 1, ≤1 year). An open-label (OL) safety study (Part 2) provided SXB treatment for up to 2 additional years. Design/Methods: Participants with narcolepsy with cataplexy (7–16 years of age) were eligible. SXB-naive participants were titrated to an optimal SXB dose and entered a 2-week stable-dose period (SD). Participants already taking SXB entered SD at their optimal dose. After SD, participants received placebo or continued SXB treatment in a 2-week, double-blind, randomized withdrawal period (DB), then entered OL treatment for up to 47 weeks. SXB-naive participants underwent polysomnography during screening (before initiating SXB), end of SD (optimal dose), and end of Part 1 (optimal dose). Participants taking SXB at study entry underwent polysomnography at screening and end of Part 1 (taking SXB). Results: Of 106 participants, 85 completed Part 1, and 44 entered Part 2. In SXB-naive participants, changes from screening to end of SD included arousals/night (median [Q1, Q3] change, −43.0 [−58.0, −17.0]), N1% (−4.6% [−7.5, −0.6]), and N3% (12.6% [7.1, 20.9]). In participants taking SXB, sleep architecture remained similar from screening to end of Part 1. Treatment-emergent adverse events (TEAEs) >10% during Part 1 were enuresis, nausea, vomiting, headache, and decreased weight. TEAEs with onset in Part 2 in >2 participants were upper respiratory tract infection and nasopharyngitis. Increased mean blood pressure was observed with no apparent relationship to SXB; other vital signs generally remained within normal range. Conclusions: Open-label SXB treatment in children with narcolepsy was associated with reduced arousals, reduced light sleep and increased deep sleep. Treatment effects and safety were consistent with adults. 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. Bogan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Bogan has served on the speakers’ bureau and participated in advisory boards for Jazz Pharmaceuticals.. Dr. Bogan has received compensation for serving on the Board of Directors of SleepMed Inc. Chief Medical Officer. Dr. Bogan has received research support from Jazz, Harmony, Avadel, Balance, Idorsia, Philips, Fresca, Merck, Axsome. Dr. Black has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals. Dr. Black has received compensation for serving on the Board of Directors of Jazz Pharmaceuticals plc. Dr. Parvataneni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ms Parvataneni is a full-time employees 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. Parvataneni 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. 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. 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.