The Efficacy and Safety of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2

NCT06523400 | Recruiting Phase 3 DMC

• 1 other identifier: MEX-DM-302
• Study Type: interventional
• Target: 176
• Locations: 6 countries
• Sites: 7

Brief Summary

A Randomized, Double-blind, Placebo-Controlled, Multi-Center Study to Investigate the Efficacy and Safety of Once Daily Mexiletine PR During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 (HERCULES study)

Conditions

Myotonic Dystrophy

Outcome Measures

Primary Outcomes (1)

• To assess the 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).

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

  26 weeks

Secondary Outcomes (19)

• To assess the 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).

  26 weeks

• Mean change in VAS

  26 weeks

• Mean change in MBS scores

  26 weeks

• Mean change in health-related quality of life

  26 weeks

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

  26 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

0 mg (matching sachet volumes to low, medium and high dose active drug)

Drug: Placebo

Mexiletine prolonged-release (PR)

ACTIVE COMPARATOR

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)

Placebo DRUG

Matching Placebo

Placebo

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;
• Presence of clinical handgrip myotonia (delayed relaxation of grip of ≥ 3 seconds after maximum voluntary contraction) at screening using VHOT;
• Be able to walk independently 10 meters (cane, walker, orthoses allowed);
• 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) 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;
• 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.
• Treatment with mexiletine within 4 weeks prior to baseline (Day 1);
• 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;
• Wheelchair-bound or bed-ridden;

Sponsors & Collaborators

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

Study Sites (7)

Laboratory for Muscle Diseases and Neuropathies

Leuven, Belgium

RECRUITING

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Ludug-Maximilians University

München, Germany

RECRUITING

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Rome, Italy

RECRUITING

University Hospital of Madrid

Madrid, Spain

RECRUITING

Saint George's University Hospitals NHS Foundation Trust

London, United Kingdom

RECRUITING

University College Hospital

London, United Kingdom

RECRUITING

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

Central Study Contacts

Nikki Adetoro

CONTACT

1 443-447-4534; nikkiadetoro@lupin.com

Study Design

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

Model Details: A multicenter, randomized, double-blind, parallel-group, placebo-controlled study intended to evaluate the efficacy and the safety of mexiletine PR in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2). The study will consist of a 4-week screening period and a 26-week treatment phase with patient visits at screening, baseline, Weeks 1, 2, 14, and 26. Eligible patients will be randomized to mexiletine or placebo in a 1:1 ratio. Approximately 80 DM1 patients (40 active: 40 placebo) are planned to be enrolled. For the purpose of sample size re-estimation, an interim analysis will be conducted when a total of 40 patients complete/early terminate the study. In addition, 16 DM2 patients are planned to be enrolled (sub-group - 8 active: 8 placebo).

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: July 26, 2024
• Study Start: February 13, 2025
• Primary Completion: March 17, 2026
• Study Completion: April 22, 2026
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); DK (1); GB (2); DE (1); BE (1); ES (1)