EFFECT OF PITOLISANT ON SYMPTOMS OF IDIOPATHIC HYPERSOMNIA DURING AN OPEN-LABEL PERIOD IN A PHASE 3 CLINICAL TRIAL

Document Type

Conference Proceeding

Publication Date

5-19-2025

Publication Title

Sleep

Abstract

Introduction: Idiopathic Hypersomnia (IH) is a rare and chronic neurological disorder. People with IH experience severe excessive daytime sleepiness (EDS), sleep inertia, and a multitude of adverse functional outcomes. Pharmacological treatments for IH are limited. Pitolisant is FDA approved for the treatment of EDS and cataplexy in adult patients and for excessive daytime sleepiness in pediatric patients ≥6 years with narcolepsy. Methods: The present analyses focused on an eight-week open-label period (OLP) that was part of a twelve-week dou ble-blind, placebo-controlled, randomized withdrawal phase 3 clinical trial to evaluate the safety and efficacy of pitolisant in adult patients with IH (NCT05156047). During the OLP, eli gible participants were titrated with pitolisant for three weeks (8.9 mg, 17.8 mg, and 35.6 mg), then began a three-week flexible dose period, and concluded with a two-week stable dose period. Efficacy measures included the Epworth Sleepiness Scale (ESS), Sleep Inertia Questionnaire (SIQ), Functional Outcomes of Sleep Questionnaire (FOSQ-10), Patient-Reported Outcomes Measurement Information System, Sleep Related Impairment (PROMIS-SRI), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Severity of EDS (PGI-S), and Clinician Global Impression of Severity of IH (CGI-S). Efficacy measures were evaluated for change from OLP baseline to the end of the eight-week OLP. Results: Two hundred and thirteen patients (mean±SD age; 39.7±12.85 years; 79.3% female) were enrolled in the trial. There was a nominally statistically significant (P< 0.0001) group mean reduction in all efficacy measures from the OLP baseline to the end of the eight-week OLP (mean±SD): ESS (16.2±3.40, 8.7±5.04; delta=-7.6±5.12); SIQ (70.0±16.91, 52.8±19.86; delta=-18.0±19.14); FOSQ-10 (11.23±2.70, 13.72±3.56; delta=2.60±3.00); PROMIS-SRI (28.7±4.85, 21.6±6.58; delta=- 7.2±6.36); IHSS (33.3±7.48, 25.8±9.44; delta=-7.7±7.94); PGI-S (3.8±0.72, 2.8±0.96; delta=-1.1±1.07); and CGI-S (3.7±0.60, 2.6±0.89; delta=-1.1±0.87). Among the 173 patients who completed the OLP (81.2%), 144 (83.2%) of them achieved a ≥3-point reduction on their ESS score, and 136 (78.6%) achieved a ≥4-point reduction on their IHSS score. Conclusion: In an 8-week OLP of a phase 3 clinical trial in adult patients with IH, pitolisant demonstrated robust improvements in EDS, sleep inertia, and a multitude of functional outcomes. A large majority of patients exhibited clinically meaningful reduc tions in their EDS and IH symptoms.

Volume

48

First Page

A376

Find It @ Sladen

Share

COinS