MEXILETINE HYDROCHLORIDE for Non-dystrophic myotonias | Myotonia congenita | Paramyotonia congenita | Sodium channel myotonia

Inclusion criteria

• {"criterion_text":"- Non-dystrophic myotonias including myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonia (SCM) confirmed genetically;\n- Male or non-pregnant female ≥16 years and older at screening;\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 cardiologistincludingcardiologist including electrocardiogram (ECG) and echocardiogram not older than 3 months prior to study entry;\n- Participants with myotonic symptoms severe enough to justify treatment;\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);"}

Exclusion criteria

• {"criterion_text":"- Are pregnant or lactating;\n- Intake of any other anti-myotonic treatment within 4 weeks prior to baseline (Day 1) or 5 half-lives, whichever is longer (e.g., metformin, propafenone, flecainide, lamotrigine, carbamazepine or any other channel-blocker/anticonvulsive drugs;\n- Use of any concomitant medications that could increase the cardiac risk or increases the risk of adverse reactions (see Section 6.8 for a complete list of prohibited concomitant medications);\n- Known allergy to mexiletine or any of the excipients 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;\n- Wheelchair-bound or bedridden;\n- 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 (see protocol Section 5.3 for a detailed list).\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 or has any other condition, which in the opinion of the Investigator, precludes the participant’s participation in the study or the participant is unlikely to comply with the protocol-defined procedures and therefore is unlikely to complete the study;\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 than NDM) that would significantly impact ambulation;\n- Severe hepatic impairment or 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;\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 hypocalcaemia, hypercalcaemia, 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;\n- Current smokers (within one month of the screening visit) (eg, cigarettes, cigars, vape/e-cigarette products, etc.);"}

Primary endpoints

• {"endpoint_text":"- Incidence of treatment emergent Adverse Events (TEAEs), treatment-related TEAEs, serious AEs, AEs of Special Interest (AESIs), and patient discontinuation rate between mexiletine PR and mexiletine IR after 12 weeks of treatment.","definition_or_measurement_approach":"Incidence and rates of TEAEs, treatment-related TEAEs, serious AEs, AESIs and discontinuation rates will be compared between treatment arms after 12 weeks of treatment; measured by collection of adverse event data during treatment and assessed for relationship to study drug."}

Secondary endpoints

• {"endpoint_text":"- Video-recording of hand opening time (VHOT)","definition_or_measurement_approach":"Video-recorded measurement of hand opening time (VHOT) as specified in protocol."}
• {"endpoint_text":"- Individualized Neuromuscular Quality of Life Questionnaire (INQoL)","definition_or_measurement_approach":"Patient-reported INQoL questionnaire scores to assess quality of life."}
• {"endpoint_text":"- Myotonia Behavior Scale (MBS)","definition_or_measurement_approach":"Assessment using the Myotonia Behavior Scale (MBS)."}
• {"endpoint_text":"- Timed “Up & Go” (TUG) Test","definition_or_measurement_approach":"Timed Up & Go test measuring functional mobility (time to stand and walk)."}
• {"endpoint_text":"- Visual Analog Scale (VAS) for myotonia/stiffness","definition_or_measurement_approach":"Patient-reported VAS score for myotonia/stiffness."}
• {"endpoint_text":"- Clinical Global Impression (CGI) – Efficacy","definition_or_measurement_approach":"Investigator-rated Clinical Global Impression for efficacy."}
• {"endpoint_text":"- Clinical Global Impression (CGI) – Tolerability Index","definition_or_measurement_approach":"Investigator-rated Clinical Global Impression tolerability index."}

Belgium

Earliest CTIS Part Ii Submission Date

27-01-2025

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

388

Number Of Sites

2

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

11-02-2025

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

373

Number Of Sites

2

Number Of Participants

4

Germany

Earliest CTIS Part Ii Submission Date

11-02-2025

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

373

Number Of Sites

1

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

03-02-2025

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

381

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Lupin Atlantis Holdings S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Eresearchtechnology Inc.

Responsibilities

Cardiac monitoring Laboratory analysis

Name

University Of Rochester

Responsibilities

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.

Name

Chillibean Limited

Responsibilities

video hand opening time (vHOT) service

Name

Ddi Llc

Responsibilities

set up, maintenance, close out of Interactive response technology (IRT) system in clinical trials.

Name

Saje Consulting

Responsibilities

To Analyze PK data

Name

Rxsource Limited

Responsibilities

IMP shipments to clinical sites , QP audit and IMP release

Name

University Of Sheffield

Responsibilities

• HGRT QMA training • VHOT training • Training on 10mwt and other functional outcome • Chillipharm training

Name

Hormosan Pharma GmbH

Responsibilities

QP audit and Comparator QP release

Third parties

• {"country":"United Kingdom","full_name":"Assistance Publique Hopitaux de Paris – Hopital Cochin","duties_or_roles":"code: 4","organisation_type":"Health care"}
• {"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":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac monitoring Laboratory analysis","organisation_type":"Pharmaceutical company"}
• {"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":"code: 1; code: 5","organisation_type":"Pharmaceutical company"}
• {"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":"United States","full_name":"Ddi Llc","duties_or_roles":"set up, maintenance, close out of Interactive response technology (IRT) system in clinical trials.","organisation_type":"Industry"}
• {"country":"United States","full_name":"Saje Consulting","duties_or_roles":"To Analyze PK data","organisation_type":"Health care"}
• {"country":"Ireland","full_name":"Rxsource Limited","duties_or_roles":"IMP shipments to clinical sites , QP audit and IMP release","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Hormosan Pharma GmbH","duties_or_roles":"QP audit and Comparator QP release","organisation_type":"Pharmaceutical company"}