Long-term Safety During a Clinical Trial of Low-Sodium Oxybate in Participants With Narcolepsy With Cataplexy (P5-13.006)

Abstract

<h3>Objective:</h3> To analyze treatment-emergent adverse events (TEAEs) during a 6-month open-label extension (OLE) of a double-blind, placebo-controlled, randomized withdrawal trial (NCT03030599) of lower-sodium oxybate (LXB; Xywav^®). <h3>Background:</h3> LXB is FDA approved for treating cataplexy or excessive daytime sleepiness in patients with narcolepsy aged ≥7 years and for treating idiopathic hypersomnia in adults. <h3>Design/Methods:</h3> Participants entered the OLE following rescreening (re-entry) after discontinuing LXB or directly following the main study (rollover). Re-entry participants initiated LXB (4.5 g/night) or, if taking sodium oxybate (SXB) during rescreening, transitioned to LXB gram-for-gram. Rollover participants initiated LXB at ≤1/2 their stable dose during the main study. Participants titrated to a maximum 9 g/night. TEAEs were assessed in those receiving ≥1 LXB dose. TEAE duration represents time from TEAE start to end date (or end of OLE, if TEAE end date unrecorded). <h3>Results:</h3> In the analysis population (N=74, mean±SD age=37.6±12.6 years, 66.2% female, 91.9% White), 27 (36.5%) re-entered, and 47 (63.5%) rolled over. Most reported ≥1 TEAE (overall, 58.1%; re-entry, 59.3%; rollover, 57.4%). Commonly reported TEAEs were headache (n=7, 9.5%; peak incidence, month 3 [n=5/72]; median [range] duration=1.0 [1–25] day), nasopharyngitis (n=6, 8.1%; peak incidence, month 6 [n=2/69]; median [range] duration=9.0 [1–24] days), and dizziness (n=5, 6.8%; peak incidence, month 1 [n=3/74]; median [range] duration=26.0 [1–181] days). TEAEs were most prevalent in month 3 (n=11/72 [15.3%] reporting a TEAE). No participant reported fall or enuresis; 1 reported nausea (rollover). Most TEAEs were mild or moderate; 2 participants had severe TEAEs (invasive ductal carcinoma [IDC], n=1; dizziness, n=1). Few participants (14.9%) had LXB-related TEAEs, most frequently dizziness (overall, 5.4%). Seven participants discontinued (re-entry, n=2; rollover, n=5), 3 due to TEAEs (IDC, n=1; apathy, n=1; sleep apnea syndrome, n=1); only apathy was treatment related. <h3>Conclusions:</h3> In this long-term study, LXB safety and tolerability were generally consistent with the known SXB safety profile. <b>Disclosure:</b> 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 $500-$4,999 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 $5,000-$9,999 for serving on a Speakers Bureau for Merck. 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. 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 Philips. The institution of Dr. Bogan has received research support from Eisai. The institution of Dr. Bogan has received research support from Fresca. 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. Dr. Bogan has received intellectual property interests from a discovery or technology relating to health care. Dr. Bogan has a non-compensated relationship as a Chair with National Sleep Foundation that is relevant to AAN interests or activities. 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. Dr. Skowronski has nothing to disclose. Ms. Chen has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Ms. Chen has received stock or an ownership interest from Jazz Pharmaceuticals. Dr. Thorpy has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Jazz. Dr. Thorpy has received publishing royalties from a publication relating to health care.