Study to Investigate the Efficacy and Safety of Mexiletine in Patients With Myotonic Dystrophy Type 1 and Type 2

• Status: Not yet recruiting
• Trial end date: 2023-07-12
• Target enrollment: 0
• Participant gender: All

Summary

A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Investigate the Efficacy and Safety of Mexiletine During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 [The MIND Study]

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Lupin Ltd.
• Treatments: Mexiletine

Criteria

Inclusion Criteria:

1. DM1 or DM2 diagnosis confirmed genetically;

2. Ability to provide informed consent;

3. Ability to understand the study requirements including intention to stay in the study until the end-of-study visit at 26 weeks of treatment;

4. Male or non-pregnant female ≥18 years of age;

5. 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, have a vasectomized partner, or are practicing abstinence;

6. No significant cardiac abnormalities as determined by a cardiologist's assessment of the electrocardiogram (ECG) and echocardiogram;

7. Capable of swallowing capsules;

8. Have sufficient finger flexor strength to grasp the handle of the dynamometer used to measure myotonia;

9. Presence of clinical handgrip myotonia (delayed relaxation of grip of ≥ 3 seconds after maximum voluntary contraction) at screening;

10. Have a Day 1 (pre-dose) handgrip dynamometer mean relaxation time of ≥1.5 seconds for the force to decline from 90% of maximum voluntary contraction force to 5%;

11. Be able to walk independently 10 meters (cane, walker, orthoses allowed);

12. DM1 patients only - Muscular impairment rating scale (MIRS) score of 2, 3, or 4.

Exclusion Criteria:

1. Are pregnant or lactating;

2. 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;

3. Severe renal impairment (glomerular filtration rate (GFR) < 30 mL/min);

4. Medical conditions which could interfere with muscle function such as infections, trauma, fractures, or planned surgery;

5. Medical conditions that could affect hand functioning including but not limited to rheumatoid arthritis, Dupuytren's contracture, hand deformity, etc.;

6. Severe arthritis or other medical condition (besides DM1/DM2) that would significantly impact ambulation;

7. High incidence of falls or fall-associated fractures (>5 falls during the past 12 months);

8. 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 the investigator;

9. Treatment with mexiletine within 4 weeks prior to baseline (Day 1);

10. Intake of any anti-myotonic treatment within 4 weeks prior to baseline (Day 1) such as propafenone, flecainide, lamotrigine, carbamazepine or any other channel-blocker/ anticonvulsive drugs;

11. Use of any concomitant medications that could increase the cardiac risk;

12. Known allergy to mexiletine or any local anesthetics;

13. Participation in another interventional clinical study during the last 3 months;

14. Wheelchair-bound or bed-ridden;

15. Any cardiac safety-associated condition including any of the following criteria detected by screening cardiac evaluations including 24-hour Holter monitoring, ECG, 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

• 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%

• 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 mexiletine and 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)

• Patients with implantable cardioverter defibrillators (ICDs) and pacemakers are excluded