MEXILETINE HYDROCHLORIDE for Myotonic dystrophy type 1 | Myotonic dystrophy type 2

Inclusion criteria

• {"criterion_text":"- DM1 or DM2 diagnosis confirmed genetically;"}
• {"criterion_text":"- Be able to walk independently 10 meters (cane, walker, orthoses allowed);"}
• {"criterion_text":"- DM1 patients only - Muscular impairment rating scale (MIRS) score of 2, 3 or 4."}
• {"criterion_text":"- 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);"}
• {"criterion_text":"- Ability to understand the study requirements including intention to stay in the study until the end-of-study visit at 26 weeks of treatment;"}
• {"criterion_text":"- Male or non-pregnant female ≥16 years of age;"}
• {"criterion_text":"- Body Mass Index (BMI) of 18.5 kg/m2 to 30 kg/m2, and weight ≥45 kg;"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- No significant cardiac abnormalities as determined by a cardiologist’s assessment;"}
• {"criterion_text":"- Have sufficient finger flexor strength to grasp the handle of the dynamometer used to measure myotonia;"}
• {"criterion_text":"- Presence of clinical handgrip myotonia (delayed relaxation of grip of ≥3 seconds after maximum voluntary contraction) at screening using VHOT;"}

Exclusion criteria

• {"criterion_text":"- Are pregnant or lactating;"}
• {"criterion_text":"- Treatment with mexiletine within 4 weeks prior to baseline (Day 1);"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- Use of any concomitant medications that could increase the cardiac risk;"}
• {"criterion_text":"- Known allergy to mexiletine or any local anesthetics;"}
• {"criterion_text":"- Participation in another interventional clinical study during the last 3 months or 5 half-lives of the investigational medicinal product, whichever is longer;"}
• {"criterion_text":"- Wheelchair-bound or bed-ridden;"}
• {"criterion_text":"- Any cardiac safety associated condition including any of the following criteria detected by screening cardiac evaluations including 24-hr Holter monitor, echocardiogram and clinical evaluations: •\tPR 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 •\tPersonal history of sustained atrial fibrillation, flutter or tachycardia (duration >30 seconds) •\tPersonal history of non-sustained (ventricular triplets or more) or sustained ventricular tachycardia •\tMyocardial infarction (acute or past) or coronary artery stenosis >50%, presence of abnormal Q waves •\tNew York Heart Association (NYHA) Class II to IV heart failure •\tLeft ventricular systolic dysfunction with ejection fraction <50% •\tSinus 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) •\tCo-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 •\tPresence of symptomatic coronary artery disease"}
• {"criterion_text":"- 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;"}
• {"criterion_text":"- Severe renal impairment (glomerular filtration rate (GFR) < 30 mL/min);"}
• {"criterion_text":"- Medical conditions which could interfere with muscle function such as infections, trauma, fractures, or planned surgery;"}
• {"criterion_text":"- Medical conditions that could affect hand functioning including but not limited to rheumatoid arthritis, Dupuytren’s contracture, hand deformity, etc.;"}
• {"criterion_text":"- Severe arthritis or medical condition (other thanDM1/DM2) that would significantly impact ambulation;"}
• {"criterion_text":"- High incidence of falls or fall-associated fractures (>5 falls during the past 12 months);"}
• {"criterion_text":"- 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 investigator;"}
• {"criterion_text":"- 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":"- Handgrip relaxation time in DM1 patients: Mean change from baseline in relaxation time of handgrip after maximal voluntary isometric contraction (MVIC) of the dominant hand using a handgrip dynamometer at Week 26.","definition_or_measurement_approach":"Mean change from baseline in handgrip relaxation time after maximal voluntary isometric contraction (MVIC) of the dominant hand measured using a handgrip dynamometer at Week 26."}

Secondary endpoints

• {"endpoint_text":"- Handgrip Dynamometer (Week 14)","definition_or_measurement_approach":"Handgrip relaxation/strength measurement using handgrip dynamometer at Week 14."}
• {"endpoint_text":"- Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain","definition_or_measurement_approach":"Patient-reported outcome assessment using the INQoL questionnaire locking domain."}
• {"endpoint_text":"- Myotonia Behavior Scale (MBS)","definition_or_measurement_approach":"Assessment using the Myotonia Behavior Scale."}
• {"endpoint_text":"- Visual Analog Scale (VAS) for myotonia","definition_or_measurement_approach":"Patient-reported Visual Analog Scale rating for myotonia."}
• {"endpoint_text":"- 10 meter Walk Test (10mWT)","definition_or_measurement_approach":"Functional capacity measure: time to walk 10 metres (10mWT)."}
• {"endpoint_text":"- DM1-Active-c","definition_or_measurement_approach":"DM1-Active-c outcome measure (no further definition provided in the record)."}

Methods

• Study website (K2_Recruitment Material_Study website and associated privacy policy, terms of use and cookie banner documents) - public-facing digital recruitment channel with country/language-specific versions (DE, FR, NL, DK, etc.).
• Referral Business Cards for HCP (K6_Recruitment Material_Referral Business Cards_HCP) - printed/provider-targeted recruitment material for healthcare professionals to refer potential participants.
• Physician Referral Letter (K7_Recruitment Material_Physician Referral letter) - targeted outreach to physicians for patient referral.
• Advocacy Outreach Tool (K8_Recruitment Material_Advocacy Outreach Tool) - materials intended for advocacy groups/outreach to patient communities.
• Informed consent and patient recruitment procedure (K1_Informed consent and patient recruitment procedure) - describes recruitment workflow and consent processes at sites.

Belgium

Earliest CTIS Part Ii Submission Date

31-07-2024

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

608

Number Of Sites

1

Number Of Participants

15

Denmark

Earliest CTIS Part Ii Submission Date

01-08-2024

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

607

Number Of Sites

2

Number Of Participants

15

Germany

Earliest CTIS Part Ii Submission Date

24-07-2024

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

615

Number Of Sites

3

Number Of Participants

44

Italy

Earliest CTIS Part Ii Submission Date

28-08-2024

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

580

Number Of Sites

4

Number Of Participants

29

Spain

Earliest CTIS Part Ii Submission Date

01-08-2024

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

607

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

Prosoft Clinical

Responsibilities

planning, project management, analysis and stats report

Name

Rxsource Limited

Responsibilities

IMP shipments to clinical sites, QP audit and IMP release

Name

Suvoda LLC

Responsibilities

Interactive Web Response Systems (IxRS)

Name

Eresearchtechnology Inc.

Responsibilities

Cardiac monitoring

Name

Saje Consulting

Responsibilities

To Analyze PK data

Third parties

• {"country":"United Kingdom","full_name":"University Of Sheffield","duties_or_roles":"• HGRT QMA training • VHOT training • Training on 10mwt and other functional outcome • Chillipharm training","organisation_type":"Educational Institution"}
• {"country":"Ireland","full_name":"Rxsource Limited","duties_or_roles":"IMP shipments to clinical sites , QP audit and IMP release","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac monitoring","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Interactive Web Response Systems (IxRS)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"University Of Rochester","duties_or_roles":"To support the delivery of the study by reviewing the study protocol to ensure clinical endpoints are appropriate for this study. In addition, she will assess all patient vHOT measurements.","organisation_type":"Educational Institution"}
• {"country":"France","full_name":"Assistance Publique Hopitaux de Paris – Hopital Cochin","duties_or_roles":"","organisation_type":"Health care"}
• {"country":"United States","full_name":"Saje Consulting","duties_or_roles":"To Analyze PK data","organisation_type":"Health care"}
• {"country":"United Kingdom","full_name":"Chillibean Limited","duties_or_roles":"video hand opening time (vHOT) service","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Ubc Late Stage (UK) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Prosoft Clinical","duties_or_roles":"planning, project management, analysis and stats report","organisation_type":"Industry"}