Effect of Pitolisant on Idiopathic Hypersomnia Symptoms During a Double-Blind Withdrawal Period in a Phase 3 Trial

Document Type

Conference Proceeding

Publication Date

5-19-2025

Publication Title

Sleep

Abstract

Introduction: Pitolisant is FDA approved for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of EDS in pediatric patients ≥6 years with narcolepsy. Given the adjacency between IH and narcolepsy and pharmacological treatments for IH are limited, the efficacy of pitolisant is being evaluated in adult patients with IH. Methods: The present analyses focused on a 4-week dou ble-blind randomized withdrawal period (DBRWP) within a 12-week phase 3 clinical trial to evaluate the safety and effi cacy of pitolisant in adult patients with IH (NCT05156047). Patients (213) initially received pitolisant for an 8-week open-la bel period (OLP) and then were assessed for their treatment response. Treatment responders (≥3-point reduction in their Epworth Sleepiness Scale [ESS] scores across the OLP) entered the DBRWP and were randomized to continue receiving dose matched pitolisant or placebo. Primary and key-secondary effi cacy measures included the ESS and the Idiopathic Hypersomnia Severity Scale (IHSS), respectively; change scores were evaluated from the end of the OLP to the end of the 4-week DBRWP for pitolisant compared with placebo. Results: Among the 173/213 patients who completed the OLP (81.2%), 139 (80.3%) of them were considered treatment responders and entered the DBRWP (mean±SD age: 39.9±11.91 years; 78.6% female). During the DBRWP the LSM difference (95% CI) in total score between the pitolisant and placebo treat ment groups was not statistically significant for the ESS (-0.85 [-2.24, 0.54]; P=0.228) and narrowly missed nominal statistical significance for the IHSS (-2.27 [-4.62, 0.08]; P=0.058). When statistically adjusting for the suspected placebo effect and sus pected regression to the mean, there was a nominally statistically significant difference between pitolisant and placebo on the ESS (-1.51 [-2.84, -0.18] P=0.026) and the IHSS (-3.20 [-5.49, -0.90] P=0.006). No new safety signals were observed. Conclusion: During the 4-week DBRWP, positive trends favor ing pitolisant were observed on the ESS and IHSS; however, they did not reach prespecified statistical significance. Ad hoc analyses showed nominally statistically significant improvements in ESS and IHSS. Pitolisant may offer a favorable benefit-risk profile and could be a potential treatment option for patients with IH

Volume

48

First Page

A375

Last Page

A376

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