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

NCT ID: NCT04700046

Last Updated: 2024-05-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-03
• Study Completion Date: 2024-08-12

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 2 [The MIND Study]

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 2 (DM1 and DM2). The study will consist of a 4-week screening period and a 26-week treatment phase with patient visits as screening, baseline, weeks 1, 2, 6, 14, 18, and 26. Eligible patients will be randomized to mexiletine or placebo in a 1:1 ratio. Approximately 158 DM1 patients (79 active: 79 placebo) are planned to be enrolled across 10-15 experienced investigational centers in Europe. In addition, up to 16 DM2 patients are planned to be enrolled (sub-group - 8 active: 8 placebo).

Study drug (mexiletine 167 mg or placebo) will be started as a once a day (QD) treatment regimen. The dose will be titrated up at the Week 1 and Week 2 visits to a maximum of 1 capsule three times a day. Depending on tolerability, the dose can also be either maintained or - if required - reduced by one dose step at any time during the study to a minimum dose of 167 mg QD.

Conditions

Myotonic Dystrophy Type 1 and Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Mexiletine

Mexiletine 167 mg (equivalent to mexiletine HCl 200 mg)

Group Type: ACTIVE_COMPARATOR

Mexiletine 167 mg

Intervention Type: DRUG

Mexiletine 167 mg (equivalent to mexiletine HCl 200 mg) immediate release, oral capsules.

Placebo

The placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine

Interventions

Mexiletine 167 mg

Mexiletine 167 mg (equivalent to mexiletine HCl 200 mg) immediate release, oral capsules.

Intervention Type: DRUG

Placebo

The placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lupin Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

MEX-DM-301

Identifier Type: -

Identifier Source: org_study_id