Abstract Details

Title Timing and Duration of Adverse Events in a Clinical Trial of Lower-Sodium Oxybate in Participants With Narcolepsy With Cataplexy

Topic Sleep

Presentation(s) P1 - Poster Session 1 (8:00 AM-9:00 AM)

Poster/Presentation
Number 1-005

Objective To evaluate treatment-emergent adverse events (TEAEs) during a double-blind, placebo-controlled, randomized-withdrawal trial (NCT03030599) of lower-sodium oxybate (LXB; Xywav^®) in participants with narcolepsy.

Background

LXB is an FDA-approved treatment for excessive daytime sleepiness or cataplexy in narcolepsy.

Design/Methods

Participants entered taking sodium oxybate (SXB) alone, SXB with other anticataplectics, other anticataplectics alone, or were anticataplectic treatment-naive. Participants taking SXB transitioned to LXB gram-for-gram; SXB-naive participants initiated LXB (4.5 g/night). TEAEs were assessed (safety population; N=201) during a 12-week open-label optimized treatment/titration period (with concurrent anticataplectic discontinuation) and 2-week stable-dose period (SDP). TEAE duration was TEAE start date to end date (inclusive of a 24-week open-label safety extension), or end of SDP if end date unrecorded.

Results

TEAEs varied by treatment at entry. Anticataplectic treatment-naive participants (n=90) reported TEAEs including headache (40%; median duration [range]=1 [1-76] day), nausea (21%; duration=9 [1-37] days), and dizziness (17%; duration=10 [1-117] days); peak incidence was week 2 (n=8/89, 9%) for headache, 3 (n=3/88, 3%) for dizziness, and 1 (n=6/90, 7%) for nausea. Decreased appetite was also reported (14%; duration=58 [2-358] days). Participants taking SXB alone (n=52) reported TEAEs including headache (33%; duration=1 [1-122] day) and diarrhea (8%; duration=41 [2-101] days); peak headache incidence was week 4 (n=4/52, 8%); diarrhea had no peak. Participants taking other anticataplectics alone (n=36) reported TEAEs including headache (39%; duration=1 [1-94] day), nausea (25%; duration=3 [1-16] days), and dizziness (25%; duration=4 [1-29] days); peak incidence was week 1 (n=3/36, 8%) for headache, 6 (n=2/32, 6%) for nausea, and 4 (n=3/33, 9%) for dizziness. One participant taking SXB with other anticataplectics (n=1/23, 4%) reported headache (weeks 1-2 and 4); one reported nausea (4%) for weeks 1-8. Discontinuations attributed to TEAEs were 20/57 (35%).

Conclusions

Most TEAEs occurred early, were consistent with SXB’s safety profile, and relatively short-lived. Participants previously taking SXB reported fewer TEAEs than SXB-naive participants.

Authors/Disclosures
Richard K. Bogan, MD (SleepMed) PRESENTER	Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Harmony. Dr. Bogan 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. Dr. Bogan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Bogan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel. Dr. Bogan has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Noctrix. 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 $500-$4,999 for serving on a Speakers Bureau for Idorsia. Dr. Bogan has received personal compensation in the range of $10,000-$49,999 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. The institution of Dr. Bogan has received research support from ZIO. The institution of Dr. Bogan has received research support from NLS. Dr. Bogan has received intellectual property interests from a discovery or technology relating to health care.
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
Michael J. Thorpy, MD (Montefiore Medical Center)	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.

��ɫ��

��ɫ��