Effects of Low-Sodium Oxybate on 24-Hour Total Sleep Time: Data From a Phase 3 Clinical Study in Adults With Idiopathic Hypersomnia
Anne Marie Morse1, Abby Chen2, Teresa Steininger2, Wayne Macfadden2
1Janet Weis Children’s Hospital, 2Jazz Pharmaceuticals
Objective:
Evaluate the effects of lower-sodium oxybate (LXB; Xywav®) on total sleep time (TST) in idiopathic hypersomnia.
Background:
Idiopathic hypersomnia is a debilitating central hypersomnolence disorder. Efficacy and safety of LXB for idiopathic hypersomnia in adults were established in a double-blind randomized withdrawal study (NCT03533114).
Design/Methods:
Participants began LXB treatment in an open-label titration and optimization period (10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP), then were randomized to placebo or continued LXB during a 2-week, double-blind, randomized withdrawal period (DBRWP). Participant-recorded daily sleep diaries from week 2 of the screening and SDP periods were analyzed. Results are reported by baseline TST in groups with <8, ≥8 to <9, or ≥9 hours of sleep per 24 hours and by treatment at study entry (treatment naive or taking alerting agents [AAs; stimulants or wake-promoting agents]).
Results:
There were 154 participants (mean±SD age, 40±14 years; 68% female). From baseline to end of SDP, estimated median reductions were observed in participants with ≥8 hours of reported baseline sleep in 24-hour TST (≥8 to <9 hours=42 minutes; ≥9 hours=115 minutes), nocturnal TST (≥8 to <9 hours=15 minutes; ≥9 hours=81 minutes), and nap duration (≥8 to <9 hours=2.5 minutes; ≥9 hours=45.2 minutes). Minimal changes were observed in 24-hour TST, nocturnal TST, and nap duration in participants with <8 hours of TST at baseline (1, 0, and 1.0 minutes, respectively). Reductions in TST were observed regardless of taking concomitant AAs in 24-hour TST (without AAs=61 minutes; with AAs=28 minutes), nocturnal TST (without AAs=32 minutes; with AAs=23 minutes), and nap duration (without AAs=11.3 minutes; with AAs=8.4 minutes). Common treatment-emergent adverse events (excluding placebo data) were nausea, headache, dizziness, anxiety, and vomiting.
Conclusions:
Open-label LXB treatment reduced TST and nap duration in participants with ≥8 hours of TST at baseline, and regardless of taking concomitant AAs.