Safety and Efficacy of KP1077 in a Phase 2, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Patients with Idiopathic Hypersomnia

Document Type

Conference Proceeding

Publication Date

9-22-2024

Publication Title

J Sleep Res

Abstract

Introduction: KP1077 (serdexmethylphenidate, a prodrug of d-methylphenidate) is under development as an oral medication for the treatment of rare sleep disorders with excessive daytime sleepiness (EDS), including idiopathic hypersomnia (IH). The objectives of this study were to assess the safety and tolerability (primary endpoint) and efficacy of KP1077 in patients with IH. Method: Sixty six adult patients with IH began KP1077 treatment in a 5-week open-label titration period (OLTP) up to the optimal dose of either 80, 160, 240 or 320 mg/day. Patients were randomized to receive their daily dose either once-per-day (QD), just before going to sleep, or twice-per-day (BID) with half the daily dose just before going to sleep and half shortly after awakening. After the 5-week OLTP, 47 qualified patients were randomized 2:1 to continue KP1077 or placebo during a 2-week, double-blind withdrawal period (DBWP) (QD: 15 KP1077, 7 placebo; BID:17 KP1077, 8 placebo). Safety assessments were based on adverse events (AEs), physical examinations, clinical laboratory tests, vital signs, and electrocardiograms. Efficacy assessments included the Epworth Sleepiness Scale (ESS), IH Severity Scale (IHSS), Sleep Inertia (SI) Visual Analog Scale (SI-VAS), and an exploratory Brain Fog (BF) Scale. Results: KP1077 was well-tolerated for both regimens and all dose levels, with most frequent AEs of insomnia, headache, anxiety, nausea, and decreased appetite. Most AEs were mild, not leading to early discontinuation. Mean total ESS decreased from 16.9 (baseline) to 7.9 (end OLTP), which was maintained in the DBWP for KP1077 but worsened to 11.3 for pooled placebo. The percentage of patients reporting SI (SI-VAS>50) decreased from 91% to 38% during the OLTP, which was maintained in the DBWP for KP1077 but increased to 47% for placebo. The BF symptom score (range 0–76 with higher values indicating more BF) decreased from 52.2 (baseline) to 29.8 (end OLTP), which was maintained in the DBWP for KP1077 and increased to 40.7 for placebo. Conclusion: KP1077 was well-tolerated in patients with IH, with AEs typical for a central nervous system stimulant mostly observed as transient. Meaningful clinical improvements in scores of ESS, IHSS, SI-VAS, and BFS were observed in both regimens.

Volume

33

Issue

S1

First Page

2

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