0592 Efficacy of Lower-Sodium Oxybate by Baseline Sleep Inertia in a Phase 3 Clinical Study in Patients With Idiopathic Hypersomnia

Abstract

Abstract Introduction Idiopathic hypersomnia is a debilitating neurologic sleep disorder. Sleep inertia (difficulty awakening) is a common symptom that can significantly impair functioning and quality of life. This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) by baseline sleep inertia in a phase 3 trial (NCT03533114). Methods Eligible participants began LXB treatment with an open-label treatment titration and optimization period (10–14 weeks), followed by a 2-week stable-dose period (SDP). Participants were randomized to placebo or continued LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). Using the visual analog scale for sleep inertia (VAS-SI), participants rated their difficulty awakening during baseline, SDP, and DBRWP on a 100-mm line with anchors at 0 (very easy) and 100 (very difficult). VAS-SI terciles comprised score segments of < 44 (group A), ≥44 to < 70 (group B), and ≥70 (group C). Efficacy assessments included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Clinical Global Impression of Severity (CGIs), and Patient Global Impression of Change (PGIc). Results Participants (A, n=34; B, n=33; C, n=32) were a mean (SD) 40.7 (13.5) years of age and primarily female (74%). At baseline, participants with the highest VAS-SI scores had numerically higher mean (SD) ESS (A=16.0 [3.1], B=15.6 [2.6], C=17.1 [2.4]) and IHSS (A=26.7 [7.7], B=34.5 [5.9], C=36.3 [5.5]) scores. Participants with the highest baseline sleep inertia were more frequently rated severely ill on the CGIs (A=17.6%, B=12.1%, C=34.4%). Baseline total sleep time trended higher with increasing VAS-SI scores. From baseline to end of SDP, mean (SD) scores decreased (improved) on the ESS (A=−9.9 [5.1], B=−9.8 [3.5], C=−10.0 [5.1]) and IHSS (A=−14.1 [9.9], B=−19.0 [9.0], C=−18.1 [9.9]), regardless of baseline sleep inertia; nearly all (99%) participants reported improvement on the PGIc. Mean (SD) VAS-SI scores decreased by 9.3 (11.9), 31.5 (14.8), and 42.8 (22.9) in groups A, B, and C, respectively, at end of SDP. Spearman correlation coefficients for VAS-SI and IHSS items assessing sleep inertia were moderate (≥0.3) to strong (≥0.6). Conclusion Participants with higher baseline sleep inertia generally had greater baseline disease burden. LXB treatment was efficacious across subgroups regardless of baseline sleep inertia. Support (if any) Jazz Pharmaceuticals.