A Study to Evaluate Pharmacokinetics, Safety, and Efficacy of Mexiletine in Adolescents and Children with Myotonic Disorders

Phase 1

• Conditions: Myotonic disorders: Nondystrophic myotonias (NDM) or myotonic dystrophies (DM, type 1 or type 2); ICD-10 code G71.1; MedDRA version: 21.1Level: LLTClassification code 10028658Term: Myotonic disordersSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2019-003757-28-FR
• Lead Sponsor: upin Europe GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-20
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

1. Male or female patients aged = 6 and < 18 years who are able to comply with the study conditions;
2. A genetically confirmed diagnosis of NDM or DM (DM1or DM2);
3. Presence of clinical symptoms of myotonia (hand grip myotonia, myotonia in the leg muscles, any other myotonia symptoms);
4. No significant cardiac abnormalities as determined by a cardiologist’s assessment of the ECG and echocardiogram performed within 3 months prior to enrolment in the study. (if not done within 3 months before trial, ECG and echocardiogram assessments will be performed at screening);
5. No history of any significant liver disorder;
6. Patients receiving mexiletine treatment agree to stop treatment at least 7 days prior to initiation of treatment with Namuscla;
7. Patients receiving other antimyotonic treatment agree to stop treatment for at least 7 times the half-life of respective drug;
8. Laboratory investigations for haematology, biochemistry, and urinalysis at screening are within normal range, or showing no clinically relevant abnormal values, as judged by the Investigator;
9. Female patients of childbearing potential must be using an acceptable form of birth control as determined by the Investigator (e.g., oral contraception, implantable, injectable/transdermal hormonal contraception, intrauterine device (IUD), barrier methods), tubal ligation or have a vasectomized partner or are practicing abstinence;
10. Patients able to provide assent to study participation and a parent or legal guardian able to sign written informed consent prior to study entry.
Are the trial subjects under 18? yes
Number of subjects for this age range: 14
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any contra-indication to mexiletine as listed in the Namuscla Summary of Product Characteristics (SmPC):
1.a. Hypersensitivity to the active substance, or to any of the excipients;
1.b. Hypersensitivity to any local anaesthetic;
1.c. Ventricular tachyarrhythmia;
1.d. Complete heart block (i.e., third-degree atrioventricular block) or any heart block susceptible to evolve to complete heart block (first-degree atrioventricular block with markedly prolonged PR interval (= 200 ms) and/or wide QRS complex (= 120 ms), second-degree atrioventricular block, bundle branch block, bifascicular and trifascicular block);
1.e. QT interval > 450ms;
1.f. Myocardial infarction (acute or past), or abnormal Q-waves;
1.g. Symptomatic coronary artery disease;
1.h. Heart failure with ejection fraction <50%;
1.i. Atrial tachyarrhythmia, fibrillation or flutter;
1.j. Sinus node dysfunction (including sinus rate < 50 bpm);
1.k. Co-administration with medicinal products inducing torsades de pointes;
1.l. Co-administration with medicinal products with narrow therapeutic index;
2. Any other neurological or psychiatric condition that might affect the assessment of the study measurements;
3. Any clinically significant illness, laboratory findings, ECG, or other clinical symptoms, which in the opinion of the Investigator could affect the patient’s optimal participation in the study;
4. Strong inducer or inhibitor of CYP2D6 or CYP1A2 within 7 days prior to study drug administration;
5. Any concurrent illness, or medications which could affect the muscle function;
6. Seizure disorder, diabetes mellitus requiring treatment by insulin;
7. Pregnant or breastfeeding;
8. Concurrent participation in any other clinical trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified