Abstract Details

Title Long-Term Efficacy and Safety of Lower-Sodium Oxybate in a Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adults With Idiopathic Hypersomnia

Topic Sleep

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

Poster/Presentation
Number 1-004

Objective To describe the long-term efficacy and safety of lower-sodium oxybate (LXB; Xywav^®) in a placebo-controlled, double-blind, randomized withdrawal study in adults with idiopathic hypersomnia (IH).

Background IH is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness; symptoms may also include prolonged nighttime sleep and severe sleep inertia. LXB is a new oxybate treatment with 92% less sodium than sodium oxybate (Xyrem^®). LXB was approved by the United States Food and Drug Administration in August 2021 for the treatment of IH in adults.

Design/Methods Eligible participants (aged 18–75 years) began LXB treatment with an open-label titration and optimization period (OLT; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). Participants were randomized to placebo or continued LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). An open-label extension period (OLE; 24 weeks) followed the DBRWP. Efficacy assessments during the OLE included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), and Patient Global Impression of Change (PGIc), all assessed during OLE week (W)2, W6, W14, and W24/early termination.

Results

The study enrolled 154 participants (safety population); 115 participants comprised the modified intent-to-treat (mITT) population. At baseline, end of SDP, and OLE W2 and W24/early termination, mean (SD) ESS scores were 15.7 (3.8), 6.1 (4.0), 6.5 (4.7), and 5.3 (3.6), respectively, and IHSS scores were 31.6 (8.3), 15.3 (8.5), 16.0 (8.9), and 14.7 (8.5), respectively (mITT population). On the PGIc, at OLT W1, end of SDP, and OLE W2 and W24/early termination, 52.3%, 93.5%, 93.2%, and 92.7% of participants, respectively, reported improvement (minimally/much/very much) relative to baseline (study day 1; safety population). Treatment-emergent adverse events (≥10%) included nausea, headache, dizziness, anxiety, and vomiting.

Conclusions LXB demonstrated long-term efficacy in adults with IH. The overall safety profile was consistent with that in narcolepsy.

Authors/Disclosures
Nancy R. Foldvary-Schaefer, DO, FAAN (Cleveland Clinic) PRESENTER	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.
Richard K. Bogan, MD (SleepMed)	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.
Isabelle Arnulf, MD (Hopital Pitie-Salpetriere)	Dr. Arnulf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ONO Pharma. Dr. Arnulf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROCHE pharma. Dr. Arnulf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IDORSIA Pharma. Dr. Arnulf has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for UCB Pharma. The institution of Dr. Arnulf has received research support from BIOPROJET pharma. The institution of Dr. Arnulf has received research support from VITALAIRE. The institution of Dr. Arnulf has received research support from French SLEEP Socity (SFRMS). The institution of Dr. Arnulf has received research support from Paris Brain Insitute. Dr. Arnulf has a non-compensated relationship as a scientific advisory with Jazz Pharma that is relevant to AAN interests or activities. Dr. Arnulf has a non-compensated relationship as a scientific advisory with Theranexus that is relevant to AAN interests or activities.
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.
Patricia Chandler	No disclosure on file
	No disclosure on file
Jed Black, MD (Jazz Pharmaceuticals)	Jed Black, MD has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Jed Black, MD has stock in Jazz Pharmaceuticals. Jed Black, MD has stock in .
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.

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