Mexiletine hydrochloride for Myotonic dystrophy type 1|Myotonic dystrophy type 2

Inclusion criteria

• {"criterion_text":"- DM1 or DM2 diagnosis confirmed genetically;\n- Ability to comprehend and willingness to sign an informed consent (ICF) or ICF of the parent(s)/legal guardian and written assent from the patient (if patient < 18 years of age);\n- Ability to understand the study requirements including intention to stay in the study until the end-of-study visit at 26 weeks of treatment;\n- Male or non-pregnant female ≥16 years of age;\n- Body Mass Index (BMI) of 18.5 kg/m2 to 30 kg/m2, and weight ≥45 kg;\n- Female patients of childbearing potential must be using a highly effective form of birth control for the duration of the study and for at least 7 days after last dose of study drug;\n- No significant cardiac abnormalities as determined by a cardiologist’s assessment;\n- Have sufficient finger flexor strength to grasp the handle of the dynamometer used to measure myotonia;\n- DM1 patients only - Muscular impairment rating scale (MIRS) score of 2, 3 or 4."}

Exclusion criteria

• {"criterion_text":"- Are pregnant or lactating;\n- Intake of any anti-myotonic treatment within 4 weeks prior to baseline (Day 1) or 5 half-lives, whichever is longer such as metformin, such as propafenone, flecainide, lamotrigine, carbamazepine or any other channel-blocker/ anticonvulsive drugs;\n- Use of any concomitant medications that could increase the cardiac risk;\n- Known allergy to mexiletine or any local anesthetics;\n- Participation in another interventional clinical study during the last 3 months or 5 half-lives of the investigational medicinal product, whichever is longer (with the exception of participation in the previous MEX-DM-302 study);\n- Wheelchair-bound or bed-ridden;\n- Any cardiac safety associated condition including any of the following criteria detected by cardiac evaluations including 24-hr Holter monitor, echocardiogram and clinical evaluations: • PR interval ≥240 ms or QRS duration ≥120 ms on resting ECG •\tPersonal history of 3rd degree or 2nd degree type 2 atrioventricular block or sinus node dysfunction with pauses ≥3 seconds, complete bundle branch block, bifascicular and trifascicular block or any heart block susceptible to evolve to complete heart block • 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%, presence of abnormal Q waves • 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)) •\tCo-administration of 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) • Co-administration of other classes of antiarrhythmics (class Ib: lidocaine, phenytoin, tocainide; class II: propranolol, esmolol, timolol, metoprolol, atenolol, carvedilol, bisoprolol, nebivolol; class IV: verapamil, diltiazem) •\tPatients with implantable cardioverter defibrillators (ICDs) and pacemakers are excluded • Presence of symptomatic coronary artery disease\n- 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;\n- Severe renal impairment (glomerular filtration rate (GFR) < 30 mL/min);\n- Medical conditions which could interfere with muscle function such as infections, trauma, fractures, or planned surgery;\n- Medical conditions that could affect hand functioning including but not limited to rheumatoid arthritis, Dupuytren’s contracture, hand deformity, etc.;\n- Severe arthritis or medical condition (other thanDM1/DM2) that would significantly impact ambulation;\n- High incidence of falls or fall-associated fractures (>5 falls during the past 12 months);\n- Preexisting elevated liver function tests > 3 times the upper limit of normal (ULN) on Day 1 (alanine transaminase (ALT)/aspartate transaminase (AST), gamma-glutamyl transferase (GGT)) and/or any abnormal chemistry, hematology or urine lab considered clinically significant by investigator;\n- Serum potassium values < 3.5 mmol/L or > 5.0 mmol/L or serum magnesium values < 1.7 mg/dL. Electrolytic imbalance such as hypokalaemia, hyperkalaemia or hypomagnesaemia may increase the proarrhythmic effects of mexiletine. Electrolyte imbalances need to be corrected before administering mexiletine and will be monitored throughout treatment."}

Primary endpoints

• {"endpoint_text":"- Incidence of Treatment Emergent Adverse Events (TEAEs), treatment-related TEAEs, serious AEs, and patient discontinuation rate.","definition_or_measurement_approach":"Safety reporting of TEAEs, treatment-related TEAEs, serious adverse events and discontinuations (standard AE collection and reporting)."}
• {"endpoint_text":"- Standard clinical laboratory evaluations, physical examinations, and vital signs","definition_or_measurement_approach":"Measured by standard clinical laboratory tests, physical examinations and recording of vital signs."}
• {"endpoint_text":"- Mean change from baseline in PR, QRS, and QTc Intervals, and average minimum heart rate by 12-lead in ECG.","definition_or_measurement_approach":"Measured using 12-lead ECG assessments comparing baseline to on-treatment values (PR, QRS, QTc intervals and average minimum heart rate)."}
• {"endpoint_text":"- Clinically relevant arrhythmic events in the Holter monitor results","definition_or_measurement_approach":"Detection of arrhythmic events via 24-hour Holter monitoring; clinically relevant arrhythmias identified in Holter results."}

Secondary endpoints

• {"endpoint_text":"- Handgrip Dynamometer","definition_or_measurement_approach":"Measurement of grip strength using a handgrip dynamometer."}
• {"endpoint_text":"- Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain","definition_or_measurement_approach":"Patient-reported outcome measured via INQoL questionnaire (locking domain)."}
• {"endpoint_text":"- Myotonia Behavior Scale (MBS)","definition_or_measurement_approach":"Assessment using the Myotonia Behavior Scale (MBS) instrument."}
• {"endpoint_text":"- Visual Analog Scale (VAS) for myotonia","definition_or_measurement_approach":"Patient self-rated myotonia severity on a visual analog scale (VAS)."}
• {"endpoint_text":"- 10 meter Walk Test (10mWT)","definition_or_measurement_approach":"Timed 10-meter walk to assess functional mobility and speed."}
• {"endpoint_text":"- DM1-Active-c","definition_or_measurement_approach":"Measured using the DM1-Active-c scale (clinical assessment instrument)."}

Methods

• Study website recruitment materials (K2_Recruitment Material_Study website; country-specific study website materials, cookie banner, privacy policy, terms of use) — digital outreach via the study website.
• Recruitment arrangements documents (K1_Recruitment arrangements) — site-level recruitment procedures described in K1 documents.
• GP Letter (L8_GP Letter_ITA) — general practitioner letter (Italy) listed among study materials.

Belgium

Earliest CTIS Part Ii Submission Date

09-09-2024

Latest Decision Or Authorization Date

14-10-2025

Processing Time Days

400

Number Of Sites

1

Number Of Participants

15

Denmark

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

395

Number Of Sites

2

Number Of Participants

15

Germany

Earliest CTIS Part Ii Submission Date

30-09-2024

Latest Decision Or Authorization Date

08-10-2025

Processing Time Days

373

Number Of Sites

3

Number Of Participants

44

Italy

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

22-01-2026

Processing Time Days

484

Number Of Sites

4

Number Of Participants

29

Spain

Earliest CTIS Part Ii Submission Date

09-09-2024

Latest Decision Or Authorization Date

09-10-2025

Processing Time Days

395

Number Of Sites

3

Number Of Participants

43

Primary sponsor

Full Name

Lupin Atlantis Holdings SA

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Suvoda LLC

Responsibilities

Interactive Web Response Systems (IxRS)

Name

Eresearchtechnology Inc.

Responsibilities

Cardiac monitoring Laboratory analysis

Name

Ubc Late Stage (UK) Limited

Responsibilities

Codes: 1, 5

Name

Rxsource Limited

Responsibilities

IMP shipments to clinical sites , QP audit and IMP release

Third parties

• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Interactive Web Response Systems (IxRS)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Ubc Late Stage (UK) Limited","duties_or_roles":"Codes: 1, 5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac monitoring Laboratory analysis","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Assistance Publique Hopitaux de Paris – Hopital Cochin","duties_or_roles":"Code: 4","organisation_type":"Health care"}
• {"country":"Ireland","full_name":"Rxsource Limited","duties_or_roles":"IMP shipments to clinical sites , QP audit and IMP release; Code: 9","organisation_type":"Pharmaceutical company"}