Efficacy of Low-sodium Oxybate by Baseline Sleep Inertia in a Phase 3 Clinical Study in Participants with Idiopathic Hypersomnia
Michael Thorpy1, Douglas Fuller2, Marisa Whalen2, Wayne Macfadden2, Yves Dauvilliers3
1Albert Einstein College of Medicine, 2Jazz Pharmaceuticals, 3Sleep and Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital
Objective:
Analyze response to low-sodium oxybate (LXB; Xywav®) by baseline sleep inertia in a phase 3 trial (NCT03533114) in participants with idiopathic hypersomnia.
Background:
Sleep inertia (difficulty awakening) is a common, debilitating symptom of idiopathic hypersomnia.
Design/Methods:
Participants received open-label LXB for 10–14 weeks, followed by a 2-week stable-dose period (SDP). Using the visual analog scale for sleep inertia (VAS-SI), participants rated their difficulty awakening during baseline and SDP on a 100-mm line with anchors at 0 (very easy) and 100 (very difficult). Baseline Idiopathic Hypersomnia Severity Scale (IHSS) item 3 and 4 scores defined sleep inertia categories of severe (≥2, both items), absent (0, both items), and mild (1 on both items, or ≥2 or 0 on 1 item only). Efficacy assessments included Epworth Sleepiness Scale (ESS), IHSS, Clinical Global Impression of Severity (CGIs), and Patient Global Impression of Change (PGIc).
Results:
Participants (absent, n=4; mild, n=46; severe, n=59) were mean (SD) 40.8 (13.6) years of age and primarily female (72%). At baseline, mean (SD) ESS scores were similar across baseline sleep inertia groups (absent=16.0 [3.7], mild=15.7 [2.8], severe=16.8 [2.7]), but participants with higher sleep inertia had higher IHSS scores (absent=19.3 [7.5], mild=28.5 [6.2], severe=36.4 [5.4]). Percentages of participants rated severely ill on CGIs were 25.0%, 10.9%, and 28.8% in the absent, mild, and severe groups, respectively. From baseline to end of SDP, mean (SD) ESS (absent=−6.5 [1.0], mild=−9.7 [4.8], severe=−10.8 [4.5]) and IHSS (absent=−6.3 [7.8], mild=−13.4 [8.1], severe=−20.8 [9.3]) scores improved across subgroups; nearly all (99%) participants reported improvement on PGIc. At end of SDP, mean (SD) VAS-SI scores decreased by 2.7 (1.8), 23.5 (20.4), and 33.1 (22.2) in the absent, mild, and severe groups, respectively.
Conclusions:
LXB improved sleep inertia, and improved sleepiness and overall idiopathic hypersomnia symptoms regardless of baseline sleep inertia.