A Study to Evaluate the Long-term Safety and Efficacy of Mexiletine in Paediatric Patients with Myotonic Disorders

Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of Mexiletine in Paediatric Patients with Myotonic Disorders Who Have Completed MEX-NM-301 and MEX-NM-302 Studies

Status

Active, not recruiting

Phases

Phase 1

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-003758-97-FR

Enrollment

Registered

2020-11-20

Start date

2020-06-24

Completion date

Unknown

Last updated

2025-03-17

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. Patients previously enrolled in parent study PIP study 4 (MEX-NM-301) or PIP Study 5 (MEX-NM-302); 2. Able and willing to provide assent to study participation and a parent or legal guardian willing to sign written informed consent prior to study entry. Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. Clinically significant laboratory abnormality, ECG or other clinical findings on physical examination indicative of a clinically significant exclusionary disease as determined by the investigator; 2. Any contra-indication to mexiletine as listed in the Namuscla Summary of Product Characteristics (SmPC): 2.a. Hypersensitivity to the active substance, or to any of the excipients; 2.b. Hypersensitivity to any local anaesthetic; 2.c. Ventricular tachyarrhythmia; 2.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); 2.e. QT interval > 450ms; 2.f. Myocardial infarction (acute or past), or abnormal Q-waves; 2.g. Symptomatic coronary artery disease; 2.h. Heart failure with ejection fraction <50%; 2.i. Atrial tachyarrhythmia, fibrillation or flutter; 2.j. Sinus node dysfunction (including sinus rate < 50 bpm); 2.k. Co-administration with medicinal products inducing torsades de pointes; 2.l. Co-administration with medicinal products with narrow therapeutic index; 3. Co- administration with antiarrhythmics; 4. Any other neurological or psychiatric condition that might affect the assessment of the study measurements; 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
Main Objective: The aim of this study is to obtain additional information regarding the long-term safety and efficacy of mexiletine for the symptomatic treatment of myotonia in paediatric subjects who have completed the initial paediatric studies. The co-primary objectives are: 1) to assess the long-term safety and tolerability of mexiletine in paediatric patients (aged 0 to < 18 years) with myotonic disorders; 2) to evaluate long-term effectiveness of oral dosing with mexiletine.;Secondary Objective: 6 to < 18 years are: 1) to evaluate the efficacy of mexiletine; 2) to evaluate efficacy and tolerability of mexiletine as measured by Clinical Global Impression (CGI) scale indices; 3) to determine changes in health-related quality-of-life. 6 months to < 6 years are: 1) to determine the changes in health-related quality-of-life; 2) to determine severity score of stiffness, pain, weakness and tiredness; 3) to determine global impression of efficacy (CGI-Efficacy index); 4) to evaluate the assessment of pain by the investigator using the FLACC (face, legs, activity, crying, and consolability) scale; 5) to determine the global impression of tolerability (CGI-Tolerability index); and 6) to evaluate daily dose of mexiletine, dose changes. < 6 months are: 1) to determine the global impression of efficacy (CGI-Efficacy index) and 2) to determine the number of apnoeic episodes throughout the study in newborns with severe neonatal episodic laryngospasm (SNEL). ;Primary end point(s): Patients aged 0 (new-borns) to 18 years: 1) Number and frequency of adverse events (AEs)/serious adverse events (SAEs); 2) Incidence of adverse events of special interest (AESI) and 3) Changes in electrocardiogram (ECG) assessments from baseline. Children and adolescents aged 6 years to < 18 years: 4) Mean change in Visual Analogue Scale (VAS) or Faces score for muscle stiffness (myotonia severity) and 5) Score of handgrip myotonia as quantitatively measured using a commercially available grip	—

Measure

Time frame

Main Objective: The aim of this study is to obtain additional information regarding the long-term safety and efficacy of mexiletine for the symptomatic treatment of myotonia in paediatric subjects who have completed the initial paediatric studies. The co-primary objectives are: 1) to assess the long-term safety and tolerability of mexiletine in paediatric patients (aged 0 to < 18 years) with myotonic disorders; 2) to evaluate long-term effectiveness of oral dosing with mexiletine.;Secondary Objective: 6 to < 18 years are: 1) to evaluate the efficacy of mexiletine; 2) to evaluate efficacy and tolerability of mexiletine as measured by Clinical Global Impression (CGI) scale indices; 3) to determine changes in health-related quality-of-life. 6 months to < 6 years are: 1) to determine the changes in health-related quality-of-life; 2) to determine severity score of stiffness, pain, weakness and tiredness; 3) to determine global impression of efficacy (CGI-Efficacy index); 4) to evaluate the assessment of pain by the investigator using the FLACC (face, legs, activity, crying, and consolability) scale; 5) to determine the global impression of tolerability (CGI-Tolerability index); and 6) to evaluate daily dose of mexiletine, dose changes. < 6 months are: 1) to determine the global impression of efficacy (CGI-Efficacy index) and 2) to determine the number of apnoeic episodes throughout the study in newborns with severe neonatal episodic laryngospasm (SNEL). ;Primary end point(s): Patients aged 0 (new-borns) to 18 years: 1) Number and frequency of adverse events (AEs)/serious adverse events (SAEs); 2) Incidence of adverse events of special interest (AESI) and 3) Changes in electrocardiogram (ECG) assessments from baseline. Children and adolescents aged 6 years to < 18 years: 4) Mean change in Visual Analogue Scale (VAS) or Faces score for muscle stiffness (myotonia severity) and 5) Score of handgrip myotonia as quantitatively measured using a commercially available grip

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Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: 1) Every 3 months (at each study visit: V1 to V9); 2) Every 3 months (at each study visit: V1 to V9); 3) Every 3 months (at each study visit: V1 to V9); 4) Every 6 months (V1, V3, V5, V7 and V9); 5) Every 6 months (V1, V3, V5, V7 and V9); 6) Every 6 months (V1, V3, V5, V7 and V9); 7) Every 6 months (V1, V3, V5, V7 and V9); 8) Every 3 months (at each study visit: V1 to V9); 9) Every 3 months (at each study visit: V1 to V9); 10) Every 6 months (V1, V3, V5, V7 and V9); 11) Every 3 months (at each study visit: V1 to V9); 12) Every 6 months (V1, V3, V5, V7 and V9).;Secondary end point(s): Patients aged 0 (new-borns) to 18 years: 1) Changes in vital signs and 2) Changes in clinical laboratory values. Children and adolescents aged 6 years to < 18 years: 3) Mean change in VAS (8 to < 18 years) or Faces (6 to < 8 years) score for severity of muscle stiffness (if not a primary endpoint) pain, weakness and fatigue; 4) Clinical myotonia assessment: 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; 5) Mean change in health-related quality-of-life as measured by the Paediatric Quality of Life (PedsQL) score; 6) Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator and 7) Mean change in Myotonia Behaviour Scale (MBS) scores. Children aged 6 months to < 6 years: 8) Mean change in Faces (4 to < 6 years only) score for severity of muscle stiffness, pain, weakness and fatigue; 9) Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator and 10) Assessment of pain by the investigator using the FLACC scale. New-borns and infants aged 0 to <6 months: 11) Clinical Global Impression (C	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: 1) Every 3 months (at each study visit: V1 to V9); 2) Every 3 months (at each study visit: V1 to V9); 3) Every 3 months (at each study visit: V1 to V9); 4) Every 6 months (V1, V3, V5, V7 and V9); 5) Every 6 months (V1, V3, V5, V7 and V9); 6) Every 6 months (V1, V3, V5, V7 and V9); 7) Every 6 months (V1, V3, V5, V7 and V9); 8) Every 3 months (at each study visit: V1 to V9); 9) Every 3 months (at each study visit: V1 to V9); 10) Every 6 months (V1, V3, V5, V7 and V9); 11) Every 3 months (at each study visit: V1 to V9); 12) Every 6 months (V1, V3, V5, V7 and V9).;Secondary end point(s): Patients aged 0 (new-borns) to 18 years: 1) Changes in vital signs and 2) Changes in clinical laboratory values. Children and adolescents aged 6 years to < 18 years: 3) Mean change in VAS (8 to < 18 years) or Faces (6 to < 8 years) score for severity of muscle stiffness (if not a primary endpoint) pain, weakness and fatigue; 4) Clinical myotonia assessment: 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; 5) Mean change in health-related quality-of-life as measured by the Paediatric Quality of Life (PedsQL) score; 6) Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator and 7) Mean change in Myotonia Behaviour Scale (MBS) scores. Children aged 6 months to < 6 years: 8) Mean change in Faces (4 to < 6 years only) score for severity of muscle stiffness, pain, weakness and fatigue; 9) Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator and 10) Assessment of pain by the investigator using the FLACC scale. New-borns and infants aged 0 to <6 months: 11) Clinical Global Impression (C

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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