Status:
RECRUITING
The Efficacy and Safety of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2
Lead Sponsor:
Lupin Ltd.
Collaborating Sponsors:
Lupin Atlantis Holdings S.A.
Conditions:
Myotonic Dystrophy
Eligibility:
All Genders
16+ years
Phase:
PHASE3
Brief Summary
A Randomized, Double-blind, Placebo-Controlled, Multi-Center Study to Investigate the Efficacy and Safety of Once Daily Mexiletine PR During 26 Weeks of Treatment in Patients with Myotonic Dystrophy T...
Detailed Description
This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled study intended to evaluate the efficacy and the safety of mexiletine PR in patients with myotonic dystrophy type 1 a...
Eligibility Criteria
Inclusion
- DM1 or DM2 diagnosis confirmed genetically;
- Ability to comprehend and willingness to sign an informed consent (ICF) or ICF of the parent(s)/legal guardian and written assent from the patient (if patient \< 18 years of age);
- Ability to understand the study requirements including intention to stay in the study until the end-of-study visit at 26 weeks of treatment;
- Male or non-pregnant female ≥16 years of age;
- Body Mass Index (BMI) of 18.5 kg/m2 to 30 kg/m2, and weight ≥45 kg;
- Female patients of childbearing potential must be using a highly effective form of birth control for the duration of the study and for at least 7 days after last dose of study drug;
- No significant cardiac abnormalities as determined by a cardiologist's assessment;
- Have sufficient finger flexor strength to grasp the handle of the dynamometer used to measure myotonia;
- Presence of clinical handgrip myotonia (delayed relaxation of grip of ≥ 3 seconds after maximum voluntary contraction) at screening using VHOT;
- Be able to walk independently 10 meters (cane, walker, orthoses allowed);
- DM1 patients only - Muscular impairment rating scale (MIRS) score of 2, 3 or 4.-
Exclusion
- Are pregnant or lactating;
- Have any one of the following medical conditions: uncontrolled diabetes mellitus, cancer other than skin cancer less than five years previously (e.g., basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) of skin allowed), multiple sclerosis, seizure disorders, or other serious medical illness;
- Severe renal impairment (glomerular filtration rate (GFR) \< 30 mL/min);
- Medical conditions which could interfere with muscle function such as infections, trauma, fractures, or planned surgery;
- Medical conditions that could affect hand functioning including but not limited to rheumatoid arthritis, Dupuytren's contracture, hand deformity, etc.;
- Severe arthritis or medical condition (other thanDM1/DM2) that would significantly impact ambulation;
- High incidence of falls or fall-associated fractures (\>5 falls during the past 12 months);
- Preexisting elevated liver function tests \> 3 times the upper limit of normal (ULN) at screening (alanine transaminase (ALT)/aspartate transaminase (AST), gamma-glutamyl transferase (GGT)) and/or any abnormal chemistry, hematology or urine lab considered clinically significant by investigator;
- Serum potassium values \< 3.5 mmol/L or \> 5.0 mmol/L or serum magnesium values \< 1.7 mg/dL. Electrolytic imbalance such as hypokalaemia, hyperkalaemia or hypomagnesaemia may increase the proarrhythmic effects of mexiletine. Electrolyte imbalances need to be corrected before administering mexiletine and will be monitored throughout treatment.
- Treatment with mexiletine within 4 weeks prior to baseline (Day 1);
- Intake of any anti-myotonic treatment within 4 weeks prior to baseline (Day 1) or 5 half-lives, whichever is longer such as metformin, such as propafenone, flecainide, lamotrigine, carbamazepine or any other channel-blocker/ anticonvulsive drugs;
- Use of any concomitant medications that could increase the cardiac risk;
- Known allergy to mexiletine or any local anesthetics;
- Participation in another interventional clinical study during the last 3 months or 5 half-lives of the investigational medicinal product, whichever is longer;
- Wheelchair-bound or bed-ridden;
- Any cardiac safety associated condition including any of the following criteria detected by screening cardiac evaluations including 24-hr Holter monitor, echocardiogram and clinical evaluations:
- PR interval ≥240 ms or QRS duration ≥120 ms on resting ECG
- Personal history of 3rd degree or 2nd degree type 2 atrioventricular block or sinus node dysfunction with pauses ≥3 seconds, complete bundle branch block, bifascicular and trifascicular block or any heart block susceptible to evolve to complete heart block
- Personal history of sustained atrial fibrillation, flutter or tachycardia (duration \>30 seconds)
- Personal history of non-sustained (ventricular triplets or more) or sustained ventricular tachycardia
- Myocardial infarction (acute or past) or coronary artery stenosis \>50%, presence of abnormal Q waves
- New York Heart Association (NYHA) Class II to IV heart failure
- Left ventricular systolic dysfunction with ejection fraction \<50%
- Sinus node dysfunction (including ECG sinus rate \<50 beats per minute (BPM))
- Co-administration of antiarrhythmics inducing torsades de pointes (class Ia: quinidine, procainamide, disopyramide, ajmaline; class Ic: encainide, flecainide, propafenone, moricizine; class III: amiodarone, sotalol, ibutilide, dofetilide, dronedarone, vernakalant)
- Co-administration of other classes of antiarrhythmics (class Ib: lidocaine, phenytoin, tocainide; class II: propranolol, esmolol, timolol, metoprolol, atenolol, carvedilol, bisoprolol, nebivolol; class IV: verapamil, diltiazem)
- Patients with implantable cardioverter defibrillators (ICDs) and pacemakers are excluded
- Presence of symptomatic coronary artery disease
Key Trial Info
Start Date :
February 13 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
April 22 2026
Estimated Enrollment :
176 Patients enrolled
Trial Details
Trial ID
NCT06523400
Start Date
February 13 2025
End Date
April 22 2026
Last Update
August 28 2025
Active Locations (6)
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1
Laboratory for Muscle Diseases and Neuropathies
Leuven, Belgium
2
Aarhus University Hospital
Aarhus, Denmark
3
Ludug-Maximilians University
München, Germany
4
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Rome, Italy