Study to Investigate the Efficacy and Safety of Mexiletine in Patients With Myotonic Dystrophy Type 1 and Type 2

NCT04700046 | Withdrawn Phase 3 DMC

• 1 other identifier: MEX-DM-301
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Investigate the Efficacy and Safety of Mexiletine During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 \[The MIND Study\]

Conditions

Myotonic Dystrophy Type 1 and Type 2

Outcome Measures

Primary Outcomes (1)

• Assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia

  To assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia in adult patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) by handgrip relaxation time in DM1 patients: Mean change from baseline (i.e., Day 1, pre-dose) in relaxation time of handgrip after 3 seconds of MVIC of the dominant hand using a handgrip dynamometer at Week 26. Mean relaxation time at each timepoint will be calculated from the first contraction in each of the 3 trials (each trial consists of 6 maximal voluntary contractions). Relaxation time for the assessment of myotonia will be calculated as the time required for the force to decline from 90% of maximum voluntary contraction force to 5%.

  6 months

Secondary Outcomes (8)

• To assess the efficacy of mexiletine on patient-reported outcomes by way of standardized instrument for measuring generic health status, EuroQol- 5 Dimension (EQ-5D).

  Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)

• To assess the efficacy of mexiletine on patient-reported outcomes by Timed "Up & Go" (TUG)

  6 months

• To assess the efficacy of mexiletine on patient-reported outcomes by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) overall

  Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)

• To assess the efficacy of mexiletine on functional capacity outcome measures by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain.

  6 months

• To assess the efficacy of mexiletine on functional capacity outcome measures by Myotonia Behavior Scale (MBS).

  Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation)

Study Arms (2)

Mexiletine

ACTIVE COMPARATOR

Mexiletine 167 mg (equivalent to mexiletine HCl 200 mg)

Drug: Mexiletine 167 mg

Placebo

PLACEBO COMPARATOR

The placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine

Drug: Placebo

Interventions

Mexiletine 167 mg DRUG

Mexiletine 167 mg (equivalent to mexiletine HCl 200 mg) immediate release, oral capsules.

Mexiletine

Placebo DRUG

The placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine

Placebo

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male or non-pregnant female ≥18 years of age
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• DM1 or DM2 diagnosis confirmed genetically;
• Ability to provide informed consent;
• 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 ≥18 years of age;
• Female patients of childbearing potential must be using an acceptable form of birth control as determined by the investigator (e.g., oral contraception, implantable, injectable/transdermal hormonal contraception, intrauterine device (IUD), barrier methods), tubal ligation, have a vasectomized partner, or are practicing abstinence;
• No significant cardiac abnormalities as determined by a cardiologist's assessment of the electrocardiogram (ECG) and echocardiogram;
• Capable of swallowing capsules;
• 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;
• Have a Day 1 (pre-dose) handgrip dynamometer mean relaxation time of ≥1.5 seconds for the force to decline from 90% of maximum voluntary contraction force to 5%;
• 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 other medical condition (besides DM1/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 the investigator;
• 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) 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;
• Wheelchair-bound or bed-ridden;
• 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:

Sponsors & Collaborators

• Lupin Ltd.: lead

MeSH Terms

Conditions

Myotonic Dystrophy

Interventions

Mexiletine

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

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenyl Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 7, 2021
• Study Start: September 3, 2021
• Primary Completion: July 1, 2024
• Study Completion: August 12, 2024
• Last Updated: May 6, 2024

Record last verified: 2024-05