Abstract-Text (inkl. Referenzen)

Paediatric myotonic dystrophy (DM) and non-dystrophic myotonias (NDM) have a significant impact on patients" quality of life. Treatment can be challenging. A short-term, open-label, non-comparative study (EudraCT 2019-003757-28) will assess the safety and efficacy of mexiletine for the treatment of myotonia in adolescents and children.

Approximately 7 patients with genetically confirmed NDM or DM1/DM2, w/o significant cardiac abnormalities on echocardiogram (ECG) or history of significant liver disorder will be enrolled. Study duration is ~12 weeks, with pharmacokinetic evaluation pre- and post-dose on Day 42. After completion, participants will be offered follow-up in an open-label 24-month extension study (EudraCT: 2019-003758-97).

Primary safety endpoints are adverse events (AEs) and serious AEs, incidence of AEs of special interest, and ECG changes from baseline. Primary efficacy endpoints are mean change in handgrip myotonia score, visual analogue score (VAS) or faces score for muscle stiffness. Secondary endpoints include mean change in VAS or faces score for muscle pain, weakness and fatigue, clinical myotonia assessment, paediatric quality of life (PedsQL) scores and Clinical Global Impression scores.

This study will inform on the safety and efficacy of treatment with mexiletine in underage patients with genetically confirmed NDM/DM1 or DM2. Pharmacokinetic data will be used to establish dosing recommendations for each paediatric age subset from 6 to <18 years old.