An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2 Who Have Completed MEX-DM-302 Study.

NCT06549400 | Enrolling By Invitation Phase 3 DMC

• 1 other identifier: MEX-DM-303
• Study Type: interventional
• Target: 176
• Locations: 6 countries
• Sites: 6

Brief Summary

This is an open-label extension study intended to evaluate the long-term safety and efficacy of mexiletine PR in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) who have completed the parent study MEX-DM-302.

Conditions

Myotonic Dystrophy

Outcome Measures

Primary Outcomes (1)

• To assess the long-term efficacy of once daily mexiletine PR for the symptomatic treatment of myotonia in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) who have completed MEX-DM-302 study.

  Handgrip relaxation time in DM1 patients by mean change in baseline of handgrip relaxation time (seconds) after maximal voluntary isometric contraction (MVIC)

  78 weeks

Secondary Outcomes (27)

• To assess the long-term safety of once daily mexiletine PR for the symptomatic treatment of myotonia in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) who have completed the MEX-DM-302 study

  78 weeks

• Mean change in VAS

  78 weeks

• Mean change in MBS scores

  78 weeks

• Mean change in health-related quality of life

  78 weeks

• Mean change in DM1-Activ-c scale (DM1 patients only)

  78 weeks

Study Arms (1)

Mexiletine prolonged-release (PR)

OTHER

Mexiletine PR 167 mg (mexiletine HCl 200 mg) Mexiletine PR 333 mg (mexiletine HCl 400 mg) OR Mexiletine PR 500 mg (mexiletine HCl 600 mg)

Drug: Mexiletine granules for prolonged-release oral suspension

Interventions

Mexiletine granules for prolonged-release oral suspension DRUG

Mexiletine PR

Mexiletine prolonged-release (PR)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• DM1 or DM2 diagnosis confirmed genetically;
• 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);
• Ability to understand the study requirements including intention to stay in the study until the end-of-study visit at 26 weeks of treatment;
• Male or non-pregnant female ≥16 years of age;
• Body Mass Index (BMI) of 18.5 kg/m2 to 30 kg/m2, and weight ≥45 kg;
• 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;
• No significant cardiac abnormalities as determined by a cardiologist's assessment;
• Have sufficient finger flexor strength to grasp the handle of the dynamometer used to measure myotonia;
• DM1 patients only - Muscular impairment rating scale (MIRS) score of 2, 3 or 4.

You may not qualify if:

• Are pregnant or lactating;
• 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;
• Severe renal impairment (glomerular filtration rate (GFR) \< 30 mL/min);
• Medical conditions which could interfere with muscle function such as infections, trauma, fractures, or planned surgery;
• Medical conditions that could affect hand functioning including but not limited to rheumatoid arthritis, Dupuytren's contracture, hand deformity, etc.;
• Severe arthritis or medical condition (other thanDM1/DM2) that would significantly impact ambulation;
• High incidence of falls or fall-associated fractures (\>5 falls during the past 12 months);
• 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;
• 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.
• 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;
• Use of any concomitant medications that could increase the cardiac risk;
• Known allergy to mexiletine or any local anesthetics;
• 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);
• Wheelchair-bound or bed-ridden;
• Any cardiac safety associated condition including any of the following criteria detected by cardiac evaluations including 24-hr Holter monitor, echocardiogram and clinical evaluations:

Sponsors & Collaborators

• Lupin Ltd.: lead
• Lupin Atlantis Holdings S.A.: collaborator

Study Sites (6)

Laboratory for Muscle Diseases and Neuropathies

Leuven, Belgium

Location

Aarhus University Hospital

Aarhus, Denmark

Location

Ludug-Maximilians University

München, Germany

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Rome, Italy

Location

University Hospital of Madrid

Madrid, Spain

Location

University College Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Myotonic Dystrophy

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label extension study intended to evaluate the continuous long-term (18 months) safety and efficacy of once daily mexiletine-prolonged release (mexiletine PR) for the symptomatic treatment of myotonia in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) who have completed the parent study MEX-DM-302. The MEX-DM-302 is a multicenter, randomized, double-blind, parallel-group, placebocontrolled study intended to evaluate the safety and efficacy of mexiletine PR in patients with DM1 and DM2) for 6 months. At the completion of the final visit in Study MEX-DM-302 patients who continue to meet the eligibility criteria will be invited to rollover into this open-label study for an additional 18 months. All patients who elect to continue into this open-label study will receive active mexiletine PR (no placebo).

Study Record Dates

• First Submitted: May 9, 2024
• First Posted: August 12, 2024
• Study Start: September 12, 2025
• Primary Completion (Estimated): May 29, 2028
• Study Completion (Estimated): July 6, 2028
• Last Updated: January 26, 2026

Record last verified: 2026-01

Locations

DK (1); BE (1); DE (1); IT (1); ES (1); GB (1)