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.
Read full abstract