A Study to Evaluate Pharmacokinetics, Safety, and Efficacy of Mexiletine in Adolescents and Children with Myotonic Disorders

An Open-label, non-Comparative Study to Evaluate the Steady-State Pharmacokinetics, Safety, and Efficacy of Mexiletine in Adolescents and Children with Myotonic Disorders

Status

Active, not recruiting

Phases

Phase 1

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-003757-28-FR

Enrollment

Registered

2020-11-20

Start date

2020-06-24

Completion date

Unknown

Last updated

2025-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Myotonic disorders: Nondystrophic myotonias (NDM) or myotonic dystrophies (DM, type 1 or type 2)

Interventions

Trade Name: Namuscla Product Name: Mexiletine 167 mg Pharmaceutical Form: Capsule, hard INN or Proposed INN: Mexiletine hydrochloride (HCl) CAS Number: 5370-01-4 Other descriptive name: MEXILETINE HYD

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Male or female patients aged = 6 and =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. Any contra-indication to mexiletine as listed in the Namuscla Summary of Product Characteristics (SmPC): 1.a. Hypersensitivity to the active substance, or to any of the excipients; 1.b. Hypersensitivity to any local anaesthetic; 1.c. Ventricular tachyarrhythmia; 1.d. Complete heart block (i.e., third-degree atrioventricular block) or any heart block susceptible to evolve to complete heart block (first-degree atrioventricular block with markedly prolonged PR interval (= 200 ms) and/or wide QRS complex (= 120 ms), second-degree atrioventricular block, bundle branch block, bifascicular and trifascicular block); 1.e. QT interval > 450ms; 1.f. Myocardial infarction (acute or past), or abnormal Q-waves; 1.g. Symptomatic coronary artery disease; 1.h. Heart failure with ejection fraction <50%; 1.i. Atrial tachyarrhythmia, fibrillation or flutter; 1.j. Sinus node dysfunction (including sinus rate < 50 bpm); 1.k. Co-administration with medicinal products inducing torsades de pointes; 1.l. Co-administration with medicinal products with narrow therapeutic index; 2. Any other neurological or psychiatric condition that might affect the assessment of the study measurements; 3. Any clinically significant illness, laboratory findings, ECG, or other clinical symptoms, which in the opinion of the Investigator could affect the patient’s optimal participation in the study; 4. Strong inducer or inhibitor of CYP2D6 or CYP1A2 within 7 days prior to study drug administration; 5. Any concurrent illness, or medications which could affect the muscle function; 6. Seizure disorder, diabetes mellitus requiring treatment by insulin; 7. Pregnant or breastfeeding; 8. Concurrent participation in any other clinical trial.

Design outcomes

Primary

Measure	Time frame
Primary end point(s): 1) Number and frequency of adverse events (AEs)/serious adverse events (SAEs); 2) Incidence of Adverse events of special interest (AESI), i.e. neurological disorders (seizure, epilepsy, vertigo, headache, paraesthesia, dysgeusia, ataxia) or gastrointestinal disorders (abdominal pain, nausea, vomiting, diarrhoea, constipation, intestinal ucer, gastrointestinal bleeding, dysphagia, oesophageal ulceration); 3) Changes in electrocardiogram (ECG) assessments from baseline; 4) Efficacy of Namuscla treatment on the clinical outcomes (change from baseline to Days 14, 28, 42 and 56, respectively), based on the following functional evaluations: Mean change in VAS or Faces score for muscle stiffness (myotonia severity); Score of handgrip myotonia as quantitatively measured using a commercially available grip dynamometer and computerised capture system in standardised conditions.;Timepoint(s) of evaluation of this end point: 1) Throughout the study while on treatment with mexiletine; 2) Throughout the study while on treatment with mexiletine; 3) Screening visit, baseline visit (Day 0), 1st titration visit (Day 14), 2nd titration visit (Day 28), PK visit (Day 42) and at the end of the study (Day 56); 4) Baseline visit (Day 0), 1st titration visit (Day 14), 2nd titration visit (Day 28), PK visit (Day 42) and at the end of the study (Day 56).;Main Objective: The co-primary objectives of this study are: 1) to evaluate the safety of mexiletine in adolescents (aged 12 to <18 years) and children (aged 6 to <12 years) for the treatment of myotonic disorders; 2) to evaluate the efficacy of mexiletine for the treatment of myotonic disorders.;Secondary Objective: The secondary objectives are: 1) to evaluate the efficacy of mexiletine for the treatment of myotonic disorders as assessed by patient-reported outcomes; 2) to evaluate effectiveness and tolerability of mexiletine as captured by Clinical Global Impression (CGI) scale indices; 3) to determine changes in he	—

Measure

Time frame

Primary end point(s): 1) Number and frequency of adverse events (AEs)/serious adverse events (SAEs); 2) Incidence of Adverse events of special interest (AESI), i.e. neurological disorders (seizure, epilepsy, vertigo, headache, paraesthesia, dysgeusia, ataxia) or gastrointestinal disorders (abdominal pain, nausea, vomiting, diarrhoea, constipation, intestinal ucer, gastrointestinal bleeding, dysphagia, oesophageal ulceration); 3) Changes in electrocardiogram (ECG) assessments from baseline; 4) Efficacy of Namuscla treatment on the clinical outcomes (change from baseline to Days 14, 28, 42 and 56, respectively), based on the following functional evaluations: Mean change in VAS or Faces score for muscle stiffness (myotonia severity); Score of handgrip myotonia as quantitatively measured using a commercially available grip dynamometer and computerised capture system in standardised conditions.;Timepoint(s) of evaluation of this end point: 1) Throughout the study while on treatment with mexiletine; 2) Throughout the study while on treatment with mexiletine; 3) Screening visit, baseline visit (Day 0), 1st titration visit (Day 14), 2nd titration visit (Day 28), PK visit (Day 42) and at the end of the study (Day 56); 4) Baseline visit (Day 0), 1st titration visit (Day 14), 2nd titration visit (Day 28), PK visit (Day 42) and at the end of the study (Day 56).;Main Objective: The co-primary objectives of this study are: 1) to evaluate the safety of mexiletine in adolescents (aged 12 to <18 years) and children (aged 6 to <12 years) for the treatment of myotonic disorders; 2) to evaluate the efficacy of mexiletine for the treatment of myotonic disorders.;Secondary Objective: The secondary objectives are: 1) to evaluate the efficacy of mexiletine for the treatment of myotonic disorders as assessed by patient-reported outcomes; 2) to evaluate effectiveness and tolerability of mexiletine as captured by Clinical Global Impression (CGI) scale indices; 3) to determine changes in he

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Secondary

Measure	Time frame
Secondary end point(s): 1) Mean change in VAS or Faces score for muscle pain, weakness and fatigue from baseline to Days 14, 28, 42 and 56, respectively; 2) Clinical myotonia assessment from baseline to Days 14, 28, 42 and 56, respectively: mean change in time to open the eyes after forced eye closure as measured on a stopwatch (when eyelid myotonia present); clinical improvement in flexor myotonia (right hand flexor muscles); and mean change in time to perform Timed-up and go (TUG) test; 3) Mean change from baseline to Day 56 in Paediatric Quality of Life (PedsQL) score; 4) Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator; 5) Mean change from baseline to Day 56 in Myotonia Behaviour Scale (MBS) scores; 6) Changes in clinical laboratory values (i.e.biochemistry, haematology, and urinalysis etc.) from baseline to Day 56; 7) Acceptability of the capsule formulation with respect to the swallowability. It will be assessed by interviewing patients and their caregivers at Day 56; 8) Palatability of alternative administration (capsule content with milk/juice or sprinkled on food) by 5-point facial hedonic scale correlated with 100-point VAS at each clinic visit; 9) Steady-state PK parameters: Cmax-ss (peak concentrations during the dosing interval at steady-state); Ctrough-ss (observed concentration at the end of a dosing interval, immediately before next administration); AUC0-tau (area under the concentration time curve for one dosing interval at steady-state); Cav-SS (average plasma concentration at steady-state); Tmax-SS (time until Cmax-SS is reached); Fluctuation (defined as 100*( Cmax-SS - Cmin-SS)/ Cav-SS).;Timepoint(s) of evaluation of this end point: 1) Baseline visit (Day 0), 1st titration visit (Day 14), 2nd titration visit (Day 28), PK visit (Day 42) and at the end of the study (Day 56); 2) Baseline visit (Day 0), 1st titration visit (Day 14), 2nd titration visit (Day 28), PK	—

Measure

Time frame

Secondary end point(s): 1) Mean change in VAS or Faces score for muscle pain, weakness and fatigue from baseline to Days 14, 28, 42 and 56, respectively; 2) Clinical myotonia assessment from baseline to Days 14, 28, 42 and 56, respectively: mean change in time to open the eyes after forced eye closure as measured on a stopwatch (when eyelid myotonia present); clinical improvement in flexor myotonia (right hand flexor muscles); and mean change in time to perform Timed-up and go (TUG) test; 3) Mean change from baseline to Day 56 in Paediatric Quality of Life (PedsQL) score; 4) Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator; 5) Mean change from baseline to Day 56 in Myotonia Behaviour Scale (MBS) scores; 6) Changes in clinical laboratory values (i.e.biochemistry, haematology, and urinalysis etc.) from baseline to Day 56; 7) Acceptability of the capsule formulation with respect to the swallowability. It will be assessed by interviewing patients and their caregivers at Day 56; 8) Palatability of alternative administration (capsule content with milk/juice or sprinkled on food) by 5-point facial hedonic scale correlated with 100-point VAS at each clinic visit; 9) Steady-state PK parameters: Cmax-ss (peak concentrations during the dosing interval at steady-state); Ctrough-ss (observed concentration at the end of a dosing interval, immediately before next administration); AUC0-tau (area under the concentration time curve for one dosing interval at steady-state); Cav-SS (average plasma concentration at steady-state); Tmax-SS (time until Cmax-SS is reached); Fluctuation (defined as 100*( Cmax-SS - Cmin-SS)/ Cav-SS).;Timepoint(s) of evaluation of this end point: 1) Baseline visit (Day 0), 1st titration visit (Day 14), 2nd titration visit (Day 28), PK visit (Day 42) and at the end of the study (Day 56); 2) Baseline visit (Day 0), 1st titration visit (Day 14), 2nd titration visit (Day 28), PK

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Countries

France

Contacts

Public ContactSenior Regulatory Affairs Manager

Lupin Healthcare (UK) Ltd.

EU-RA@lupin.com+441565751378

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026