Status:
WITHDRAWN
Study to Investigate the Efficacy and Safety of Mexiletine in Patients With Myotonic Dystrophy Type 1 and Type 2
Lead Sponsor:
Lupin Ltd.
Conditions:
Myotonic Dystrophy Type 1 and Type 2
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief 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...
Detailed Description
This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled study intended to evaluate the safety and efficacy of mexiletine in patients with myotonic dystrophy type 1 and type...
Eligibility Criteria
Inclusion
- DM1 or DM2 diagnosis confirmed genetically;
- Ability to provide informed consent;
- 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 ≥18 years of age;
- 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;
- No significant cardiac abnormalities as determined by a cardiologist's assessment of the electrocardiogram (ECG) and echocardiogram;
- Capable of swallowing capsules;
- 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;
- 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%;
- 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 other medical condition (besides DM1/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 the investigator;
- 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) 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;
- Wheelchair-bound or bed-ridden;
- 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
Key Trial Info
Start Date :
September 3 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 12 2024
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT04700046
Start Date
September 3 2021
End Date
August 12 2024
Last Update
May 6 2024
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