Long-Term Safety and Effectiveness of Pitolisant Use in Adult Patients with Idiopathic Hypersomnia (IH)

Document Type

Conference Proceeding

Publication Date

5-19-2025

Publication Title

Sleep

Abstract

Introduction: Pitolisant is being evaluated for use in adult patients with IH in two phase 3 clinical trials, a double-blind randomized withdrawal (DBRW) and an open-label extension (OLE). The present analyses focused on the safety and effective - ness of long-term administration of pitolisant in adult patients with IH across 13 months. The OLE study is ongoing. Methods: Open-label data were integrated across two con - tiguous phase 3 clinical trials (DBRW: NCT05156047; OLE: NCT05458128). Safety measures included treatment-related treatment-emergent adverse events (TR-TEAEs). Effectiveness measures included the Epworth Sleepiness Scale (ESS); Idiopathic Hypersomnia Severity Scale (IHSS); Patient Reported Outcomes Measurement Information System, Sleep Related Impairment-8a (PROMIS-SRI); Patient Sleep Inertia Questionnaire (SIQ); Functional Outcomes of Sleep Questionnaire (FOSQ-10); Patient Global Impression of Severity of EDS (PGI-S); and Clinician Global Impression of Severity of IH (CGI-S). Effectiveness measures were assessed at baseline, Month 2, Month 4, Month 10, and Month 16. Results: The safety population included 213 patients who received at least one dose of pitolisant (mean±SD age, 39.7±12.85 years; 79.3% female). The median duration of pitolisant exposure was 39.14 weeks (range: 0.71-93.29 weeks) and the median maximum pitolisant dosage was 35.6 mg (median [range: 8.9-35.6 mg]). Among this population, 102 participants (47.9%) experienced a TR-TEAE; most frequent TR-TEAEs were headache (17.8%), insomnia (16.0%), and abnormal dreams (5.2%). The effective - ness population included 119 adult patients who enrolled in both trials (mean±SD age, 40.1±11.96 years; 79.8% female). Generally, the sample size remained stable across timepoints. All effectiveness measures demonstrated a nominally statistically sig - nificant reduction (P< 0.0001) from study baseline at every time - point. Effectiveness measures are reported as baseline mean±SD, and change from baseline across all timepoints (range: lowest, highest change across endpoints [mean±SD]): ESS, 16.6±2.99 (-8.4±4.46, -9.7±4.69); IHSS, 33.7±7.10 (-9.8±7.56, -13.4±8.66); PROMIS-SRI, 64.16±4.89 (-8.35±7.26, -10.11±5.56); SIQ, 71.8±17.14 (-21.2±17.21, -24.9±18.91); FOSQ-10, 11.14±2.77 (3.31±2.99, 4.24±3.07); PGI-S, 3.9±0.74 (-1.2±0.99, -1.4±0.95); and CGI-S, 3.6±0.60 (-1.2±0.89, -1.3±0.78). Conclusion: Pitolisant was well-tolerated, and the safety profile was consistent with the established safety profile for patients with narcolepsy. Pitolisant showed clinically meaningful and sustained improvements in multiple symptoms of IH across a >1-year dosing period

Volume

48

First Page

A376

Last Page

A377

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