0389 Efficacy of Lower-Sodium Oxybate in the Treatment of Idiopathic Hypersomnia: Evaluation of Response Based on the Epworth Sleepiness Scale Score

Abstract

Abstract Introduction Idiopathic hypersomnia is a debilitating neurologic sleep disorder characterized by excessive daytime sleepiness (EDS), with sleep inertia and prolonged nighttime sleep as key symptoms in many patients. The Epworth Sleepiness Scale (ESS) is an 8-item self-report questionnaire (0–24 score range; higher scores indicate greater EDS). An ESS total score ≤10 is considered normal. The minimum clinically important difference (MCID) for narcolepsy is considered to be a decrease of ≥2 points; the MCID in idiopathic hypersomnia has not been established. This post hoc analysis evaluated response to lower-sodium oxybate (LXB; Xywav®) treatment on ESS scores in a phase 3 clinical trial (NCT03533114). Methods Eligible participants with idiopathic hypersomnia began LXB treatment with an open-label titration and optimization period (OLT; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). The ESS was completed at baseline, during OLT (week [W]1, W4, W8, and end of OLT), and end of SDP. Response was defined as ESS total score ≤10 or decrease in total ESS score of ≥4 points after open-label LXB treatment. Results Participants were treatment naive (n=47) or taking alerting agents other than sodium oxybate at study entry (stable doses ≥2 months; n=62). At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of total ESS score ≤10 was 13.0%, 55.3%, 70.2%, 85.1%, and 87.2% (treatment-naive participants), respectively, and 21.0%, 56.5%, 65.6%, 74.2%, and 83.9% (participants taking alerting agents), respectively. At W1, W4, W8, end of OLT, and end of SDP, the percentage of participants achieving a response of total ESS score decrease of ≥4 points was 26.1%, 68.1%, 76.6%, 87.2%, and 87.2% (treatment-naive participants), respectively, and 33.9%, 64.5%, 78.7%, 88.7%, and 95.2% (participants taking alerting agents), respectively. Treatment-emergent adverse events (≥10%) included nausea, headache, dizziness, anxiety, and vomiting. Conclusion Over 80% of participants achieved a clinically meaningful response based upon ESS total score ≤10, and up to 95% demonstrated a decrease in total ESS score of ≥4 points at end of SDP. The response rate increased over the study period. The safety profile of LXB was consistent with that observed in narcolepsy. Support (If Any) Jazz Pharmaceuticals.