Myotonic Dystrophy Type 1 and Type 2 Clinical Trial
— MINDOfficial 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]
| Verified date | May 2024 |
| Source | Lupin Ltd. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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]
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | August 12, 2024 |
| Est. primary completion date | July 1, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Lupin Ltd. |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia | To assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia in adult patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) by handgrip relaxation time in DM1 patients: Mean change from baseline (i.e., Day 1, pre-dose) in relaxation time of handgrip after 3 seconds of MVIC of the dominant hand using a handgrip dynamometer at Week 26. Mean relaxation time at each timepoint will be calculated from the first contraction in each of the 3 trials (each trial consists of 6 maximal voluntary contractions). Relaxation time for the assessment of myotonia will be calculated as the time required for the force to decline from 90% of maximum voluntary contraction force to 5%. | 6 months | |
| Secondary | 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). | The EQ-5D is a multi-attribute utility instrument for measuring health-related quality of life. EQ-5D: EuroQol - 5 dimensions (Health-related quality of life measure developed by EuroQol group). The index score is calculated by software hence minimum/maximum or better/worse not applicable. The EQ-5D assessments will be collected on Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation). | Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation) | |
| Secondary | To assess the efficacy of mexiletine on patient-reported outcomes by Timed "Up & Go" (TUG) | The TUG Test (Podsiadlo, 1991; Trip 2009a) measures, in seconds, the time taken by an individual to stand up from a standard arm chair (approximate seat height of 46 cm, arm height 65 cm), walk a distance of 3 meters (approximately 10 feet), turn, walk back to the chair, and sit down. | 6 months | |
| Secondary | To assess the efficacy of mexiletine on patient-reported outcomes by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) overall | INQoL- Individualized neuromuscular quality of life questionnaire. Higher score represents worsening and lower score represents better. Minimum/maximum- not applicable. The INQoL overall questionnaire will be completed on Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation) | Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation) | |
| Secondary | To assess the efficacy of mexiletine on functional capacity outcome measures by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain. | To assess the efficacy of mexiletine on functional capacity outcome measures by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain.INQoL- Individualized neuromuscular quality of life questionnaire. Higher score represents worsening and lower score represents better. Minimum/maximum- not applicable. | 6 months | |
| Secondary | To assess the efficacy of mexiletine on functional capacity outcome measures by Myotonia Behavior Scale (MBS). | MBS was originally developed by Budzynski, Stoyva, Adler and Mullaney as a pain measurement instrument (Budzynski, 1973). The patient chooses one out of six framed sentences, which most closely describe the impact of the stiffness on everyday life. MBS: myotonia behavior scale, score ranges 0 - 5. Lower score is better and higher score is worsening. The MBS assessments will be completed on Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation) | Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation) | |
| Secondary | To assess the efficacy of mexiletine on functional capacity outcome measures by Visual Analog Scale (VAS) for myotonia. | The construction of VAS in this study is an absolute measure, with a straight, horizontal, 10 cm line having the endpoints "No stiffness at all" and "Stiffness as worst possible". The patient responds with a score on the line to the nearest millimeter on a 100-point scale. The VAS will be completed on Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation) | 6 months | |
| Secondary | To assess the efficacy of mexiletine on functional capacity outcome measures by 10 meter Walk Test (10mWT). | the 10mWT is a performance-based test assessing walking in two different conditions, own preferred speed and maximum speed, over a short distance. The time taken to walk 10 meters at usual comfortable and maximum speed is recorded with a stopwatch. | 6 months | |
| Secondary | To assess the efficacy of mexiletine on functional capacity outcome measures by DM1-Active-c. | DM1-Activ-c scale is a disease-specific, Rasch-built scale, developed as a patient-reported outcome measure of capacity for activity and social participation with a 0-100 interval range (a higher score indicates higher capacity) (Hermans, 2015).VAS- Visual analogue scale. Score ranges 0-100. Lower is better and higher is worsening. The DM1-Activ-c scale score will be collected on Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation) | Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation) |