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

• Register: ClinicalTrials.gov
• Last refreshed on: 13 May 2024
• Main ID: NCT04700046
• Date of registration: 05/01/2021
• Prospective Registration: Yes
• Primary sponsor: Lupin Ltd.
• Public title: Study to Investigate the Efficacy and Safety of Mexiletine in Patients With Myotonic Dystrophy Type 1 and Type 2 MIND
• Scientific title: 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]
• Date of first enrolment: September 3, 2021
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/ct2/show/NCT04700046
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Myotonic Dystrophy Type 1 and Type 2

Intervention(s)

Drug: Mexiletine 167 mg

Drug: Placebo

Primary Outcome(s)

Assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia [Time Frame: 6 months]

Secondary Outcome(s)

To assess the efficacy of mexiletine on patient-reported outcomes by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) overall [Time Frame: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)]

To assess the efficacy of mexiletine on functional capacity outcome measures by 10 meter Walk Test (10mWT). [Time Frame: 6 months]

To assess the efficacy of mexiletine on functional capacity outcome measures by DM1-Active-c. [Time Frame: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)]

To assess the efficacy of mexiletine on patient-reported outcomes by way of standardized instrument for measuring generic health status, EuroQol- 5 Dimension (EQ-5D). [Time Frame: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)]

To assess the efficacy of mexiletine on patient-reported outcomes by Timed "Up & Go" (TUG) [Time Frame: 6 months]

To assess the efficacy of mexiletine on functional capacity outcome measures by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain. [Time Frame: 6 months]

To assess the efficacy of mexiletine on functional capacity outcome measures by Myotonia Behavior Scale (MBS). [Time Frame: Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation)]

To assess the efficacy of mexiletine on functional capacity outcome measures by Visual Analog Scale (VAS) for myotonia. [Time Frame: 6 months]

Secondary ID(s)

MEX-DM-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors