Open Label Study in Adolescents and Children With Myotonic Disorders
Myotonic Dystrophy
About this trial
This is an interventional treatment trial for Myotonic Dystrophy
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged ≥ 6 and < 18 years who are able to comply with the study requirements
- A genetically confirmed diagnosis of NDM or DM (DM1or DM2)
- Presence of clinical symptoms of myotonia (hand grip myotonia, myotonia in the leg muscles, any other myotonia symptoms)
- 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, electrocardiogram (ECG) and echocardiogram assessments will be performed at screening)
- No history of any significant liver disorder
- Patients receiving mexiletine treatment agree to stop treatment at least 7 days prior to initiation of treatment with Namuscla
- Patients receiving other antimyotonic treatment agree to stop treatment for at least 7 times the half-life of respective drug
- Laboratory investigations for haematology, biochemistry, and urinalysis at screening are within the normal range, or showing no clinically relevant abnormal values, as judged by the Investigator.
- 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 are practicing abstinence.
- Patients able to provide assent to study participation and a parent or legal guardian to sign the written informed consent prior to study entry.
Exclusion Criteria:
Any contra-indication to mexiletine as listed in the Namuscla Summary of Product Characteristics (SmPC):
- Hypersensitivity to the active substance, or to any of the excipients
- Hypersensitivity to any local anaesthetic
- Ventricular tachyarrhythmia
- 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),
- QT interval > 450ms
- Myocardial infarction (acute or past), or abnormal Q-waves
- Symptomatic coronary artery disease
- Heart failure with ejection fraction <50%
- Atrial tachyarrhythmia, fibrillation or flutter
Sinus node dysfunction (including sinus rate < 50 bpm)
• Co-administration with medicinal products inducing torsades de pointes (class Ia, Ic, III antiarrhythmics): Co-administration of mexiletine and antiarrhythmics inducing torsades de pointesclass Ia: quinidine, procainamide, disopyramide, ajmaline; class Ic: encainide, flecainide, propafenone, moricizine; class III: amiodarone, sotalol, ibutilide, dofetilide, dronedarone, vernakalant) increases the risk of potentially lethal torsades de pointes.
- Co-administration with medicinal products with narrow therapeutic index
- Any other neurological or psychiatric condition that might affect the study assessments
- 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
- Strong inducer or inhibitor of CYP2D6 or CYP1A2 within 7 days prior to study drug administration
- Any concurrent illness, or medications which could affect the muscle function
- Seizure disorder, diabetes mellitus requiring treatment by insulin
- Pregnant or breastfeeding
- Concurrent participation in any other clinical trial.
Sites / Locations
- Hôpital Necker-Enfants-MaladesRecruiting
Arms of the Study
Arm 1
Other
Cohort 1 and 2
7 patients aged 12 to < 18 years , inclusive in cohort-1 7 patients aged 6 to < 12 years, inclusive in cohort-2