500 Correlation of the Idiopathic Hypersomnia Severity Scale With Other Measures of Sleep Parameters in a Phase 3 Trial

Abstract

Introduction: The Idiopathic Hypersomnia Severity Scale (IHSS) is a 14-item, self-reported questionnaire that assesses core Idiopathic Hypersomnia (IH) symptom severity. The relationship between IHSS scores and other IH symptom measures, such as the Epworth Sleepiness Scale (ESS; measures daytime sleepiness), sleep inertia visual analog scale (VAS-SI; measures sleep inertia), and Patient Global Impression of Change (PGIc; measures patients' self-assessed change in symptoms), has not been established. This post hoc analysis analyzed correlations between the IHSS and ESS, VAS-SI, and PGIc using data from a clinical trial (NCT03533114) evaluating lower-sodium oxybate (LXB; Xywav™) for the treatment of IH. Methods: During a clinical trial, the IHSS (0-50 score range) and ESS (0-24 score range) were completed at baseline; the IHSS, ESS, and PGIc (ordinal, 7 categories) were completed during an openlabel treatment titration and optimization period (OLTTOP), after the OLTTOP, after a stable-dose period (SDP), and after a double-blind, randomized withdrawal period (DBRWP). The VAS-SI (0-100 score range) was completed during screening, SDP, and DBRWP. Correlation coefficients (rs) for IHSS vs ESS and VAS-SI were estimated from the within-subject variance matrix using a repeated-measures linear mixed model (LMM). The correlation between changes in IHSS score and PGIc was assessed using a Kruskal-Wallis test. Results: IHSS scores correlated positively with ESS scores (rs [95% CI], 0.77 [0.73, 0.81]) and VAS-SI scores (0.69 [0.63, 0.75]). IHSS total score change was correlated with PGIc rank (chi-square with 6 degrees of freedom = 595.8, nominal P<0.001). The LMM showed that a 3-point change in ESS score corresponded to an average 3.99-point change in IHSS score; a 10-point change in VAS-SI score corresponded to an average 3-point change in IHSS score. Participants very much improved in the PGIc had a -12.13 (95% CI: -13.23, -11.04) expected change in IHSS score. Participants much improved in the PGIc had a -8.39 (95% CI: -9.30, -7.48) expected change in IHSS score. Conclusion: IHSS scores or score changes strongly correlated with individual instruments assessing excessive daytime sleepiness, sleep inertia, and self-reported global symptoms, suggesting that the IHSS is a reliable, comprehensive measure of these symptoms of IH.