Abstract Details

Title Changes in Cataplexy Frequency by Therapy at Study Entry in a Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of JZP-258 in Adults With Narcolepsy With Cataplexy

Topic Sleep

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 5-011

Objective To report cataplexy frequency during titration of JZP-258 and taper/discontinuation of other anticataplectics in a phase 3 study.

Background Sodium oxybate (SXB) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy. JZP-258 is an oxybate product candidate with 92% less sodium.

Design/Methods Participants (18–70 years of age with narcolepsy with cataplexy) began a 12-week, open-label optimized treatment and titration period (OLOTTP): after initial JZP-258 titration (≥2 weeks), prior anticataplectics were tapered/discontinued by week 10. A 2-week stable-dose period (SDP) and 2-week, placebo-controlled, double-blind, randomized-withdrawal period (DBRWP) followed. Primary efficacy assessment was change in weekly number of cataplexy attacks from SDP to DBRWP.

Results Safety was analyzed for all 201 enrolled participants; 134 participants received randomized study treatment. Median (Q1, Q3) weekly cataplexy at week 1, end of OLOTTP, and end of SDP by anticataplectic therapy at entry was: SXB only (n=41), 2.0 (0.0, 10.0), 1.0 (0.0, 7.0), and 1.0 (0.0, 4.0); SXB+other anticataplectics (n=14), 0.6 (0.0, 3.0), 2.2 (0.0, 31.5), and 2.0 (0.0, 23.0); other anticataplectics (n=21), 3.5 (1.0, 9.3), 2.3 (0.0, 9.0), and 2.0 (0.0, 11.2); anticataplectic naive (n=58), 5.8 (1.4, 12.6), 2.0 (0.0, 5.0), and 0.9 (0.0, 5.3). Common adverse events (AEs) with JZP-258 included headache (41/201; 20.4%), nausea (26/201; 12.9%), and dizziness (21/201; 10.4%). Serious treatment-related AEs were reported in 2 participants (confusional state and visual hallucination after unrelated accidental JZP-258 overdose; muscle enzymes increased 1 day after end of placebo treatment).

Conclusions In participants taking SXB only at study entry, cataplexy remained controlled with JZP-258 treatment. In anticataplectic-naive participants, cataplexy decreased with JZP-258 treatment. In participants taking other anticataplectics with or without SXB at study entry, cataplexy increased with anticataplectic taper/discontinuation, then stabilized during OLOTTP and SDP. The overall AE profile of JZP-258 was consistent with SXB.

Authors/Disclosures
Michael J. Thorpy, MD (Montefiore Medical Center) PRESENTER	Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avadel. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for alkermes. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Harmony. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for centessa. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axsome. Dr. Thorpy has received publishing royalties from a publication relating to health care.
	No disclosure on file
Richard K. Bogan, MD (SleepMed)	Dr. Bogan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Jazz Pharmaceutical . Dr. Bogan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Takeda. Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axsome . Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Harmony. Dr. Bogan has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Jazz. Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Axsome. Dr. Bogan has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Jazz. The institution of Dr. Bogan has received research support from Jazz Pharmaceuticals. The institution of Dr. Bogan has received research support from Harmony . The institution of Dr. Bogan has received research support from Eisai. The institution of Dr. Bogan has received research support from Avadel. The institution of Dr. Bogan has received research support from Takeda. The institution of Dr. Bogan has received research support from Suven. The institution of Dr. Bogan has received research support from Axsome. The institution of Dr. Bogan has received research support from Merck. The institution of Dr. Bogan has received research support from Liva Nova. The institution of Dr. Bogan has received research support from Nyxoah. Dr. Bogan has received research support from Bayer. Dr. Bogan has received intellectual property interests from a discovery or technology relating to health care.
Markku Partinen, MD, PhD, FAAN (Helsinki Sleep Clinic)	No disclosure on file
	No disclosure on file
Nancy R. Foldvary-Schaefer, DO, FAAN (Cleveland Clinic)	Dr. Foldvary-Schaefer has received personal compensation in the range of $10,000-$49,999 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.
Roman Skowronski, MD, PhD	Dr. Skowronski has nothing to disclose.
	No disclosure on file
Franck Skobieranda, MD	Dr. Skobieranda has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Skobieranda has received stock or an ownership interest from Jazz Pharmaceuticals.
Yves Dauvilliers, MD, PhD (Hopital Gui De Chaulliac)	Yves Dauvilliers, MD, PhD 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, MD, PhD 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, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alkermes. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Centessa. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bioprojet. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Harmony Bioscience.

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