A Phase 3 interventional study of Mexiletine in Myotonic Dystrophy, sponsored by Lupin Ltd.. Completed at 1 site in France. Open to participants aged 6 Years to 18 Years. Per ClinicalTrials.gov, last updated 2024-11-25.
Sponsored by Lupin Ltd. · Phase 3, Interventional, and Treatment
This is an open-label, multi-centre, single arm, interventional study to describe the steady-state PK, safety, and efficacy of mexiletine in paediatric patients (6 to \<18 years of age) with myotonic disorders.
This is an open-label, multi-centre, single arm, interventional study to describe the steady-state PK, safety, and efficacy of mexiletine in paediatric patients (6 to \<18 years of age) with myotonic disorders.
Patients who meet the eligibility criteria will be enrolled stepwise, sequentially in 2 cohorts by age groups.
Cohort 1 - Adolescents aged 12 to \<18 years, will be enrolled first. If no safety concerns are observed (based on data evaluation by the Data Safety Monitoring Board [DSMB]), and the dose for the age group 6 to \<12 years is confirmed by PK model, enrolment for Cohort 2 will begin.
Cohort 2 - Children aged 6 to \<12 years, will be enrolled. The overall treatment duration for each cohort will be approximately 56 days (8 weeks): a dose titration phase of 4 weeks and the maintenance phase of 4 weeks. The overall study duration would be approximately 22 months.
Dose titration phase: In this phase, patients will receive mexiletine starting at an age appropriate dose (as evaluated by the investigator and based on body weight) at a frequency of once a day. Dose will be up-titrated every 14 days based on tolerability of mexiletine up to a maximum of three-times a day as assessed by investigator.
Maintenance phase: During the maintenance phase, patients will continue to receive mexiletine at the best-tolerated dose from the titration phase for further 4 weeks. Following completion, all participants will be offered follow-up in PIP Study 7 (MEX-NM-303) (EudraCT: 2019-003758-97).
125 studies on the registry are indexed under Myotonic Dystrophy; 51 are open to participants now.
This study's enrollment of 12 is below the median of 41 across 66 interventional studies indexed under Myotonic Dystrophy.
Browse Myotonic Dystrophy studies →Lupin Ltd. is the lead sponsor of 16 studies on the registry; 5 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Any contra-indication to mexiletine as listed in the Namuscla Summary of Product Characteristics (SmPC):
Sinus node dysfunction (including sinus rate \< 50 bpm)
7 patients aged 12 to \< 18 years , inclusive in cohort-1 7 patients aged 6 to \< 12 years, inclusive in cohort-2
Drug: Mexiletine
Patients will be enrolled sequentially into 2 cohorts. Cohort 1 - (patients aged 12 to \< 18 years): approximately 8 weeks - 4 weeks of dose titration period + 4 weeks of maintenance period. Cohort 2 - (patients aged 6 to \< 12 years,): approximately 8 weeks - 4 weeks of dose titration period + 4 weeks of maintenance period. Enrolment for Cohort 2 will begin after initial safety assessment of patients in Cohort 1 by the DSMB and no safety concerns are observed. The dose level for cohort 2 will be confirmed by PK modelling study.
Also known as: Namuscla ™
Number and frequency of adverse events (AEs)/serious adverse events (SAEs)
Number and frequency of adverse events (AEs)/serious adverse events (SAEs), throughout the study while on treatment with Namuscla
Time frame: Baseline to Day 56
Incidence of adverse events of special interest (AESI)
Incidence of adverse events of special interest (AESI)
Time frame: Baseline to Day 56
Changes in ECG assessments from baseline
On resting ECG any alteration will be noted: * Mild ECG abnormalities: PR interval ≥200 ms and QRS duration ≥100 ms * Severe ECG abnormalities: PR interval ≥240 ms, QRS duration ≥120 ms, second or third degree AV block and a rhythm other than sinus
Time frame: Baseline to Day 56
Efficacy of Namuscla treatment on the clinical outcomes based on the following functional evaluation mean change in Visual Analogue Scale (VAS) for muscle stiffness.
Mean change in Visual Analogue Scale (VAS) for muscle stiffness. The VAS is constructed as an absolute measure, with a 10 cm straight horizontal line having the endpoints "no stiffness at all" and "stiffness as worst possible". The patient's responses will be scored on the line to the nearest millimetre (a 100-point scale). (myotonia severity).
Time frame: Baseline to Day 56
Efficacy of Namuscla treatment on the clinical outcomes(change from baseline to Days 14, 28, 42 and 56, respectively) based on the following functional evaluation
The score of handgrip myotonia as quantitatively measured using a commercially available grip dynamometer and computerised capture system. In standardised conditions (i.e. in a room at controlled temperature, after a definite period of rest), maximum voluntary contractions following forced right hand grip will be recorded and the time to relax from 90% to 5% of maximal force will be determined using automated analysis software
Time frame: Baseline to Day 56
Mean change in VAS score for muscle pain, weakness and fatigue
The VAS is constructed as an absolute measure, with a 10 cm straight horizontal line having the endpoints "no stiffness at all" and "stiffness as worst possible". The patient's responses will be scored on the line to the nearest millimetre (a 100-point scale). The score of stiffness severity as self-reported by the patient on a 10-point VAS will be used for adolescents and children older than 8 years and will be summarised descriptively by visit
Time frame: Baseline - Day 56
Clinical myotonia assessment for mean change in time to open the eyes
Mean change in time to open the eyes after forced eye closure as measured on a stopwatch (when eyelid myotonia present). Subjects will be asked to squeeze their eyes closed for 5 seconds then rapidly open them for 5 seconds then rapidly open. Five trials of each manoeuvre will be performed in sequence at each visit and the time measured on a stopwatch
Time frame: Baseline - Day 56
Clinical myotonia assessment of clinical change in flexor myotonia
Clinical change in flexor myotonia (right hand flexor muscles). Subjects will be asked to make a tight fist for 5 seconds then rapidly open. Five trials of each manoeuvre will be performed in sequence at each visit and the time measured on a stopwatch
Time frame: Baseline - Day 56
Clinical myotonia assessment of mean change in time to perform Timed-up and go (TUG) test
Mean change in time to perform Timed-up and go (TUG) test. Measures, in seconds, the time taken by an individual to stand up from a standard arm chair (approximate seat height of 46 cm, arm height 65 cm), walk a distance of 3 meters (approximately 10 feet), turn, walk back to the chair, and sit down.
Time frame: Baseline - Day 56
Mean change in health-related quality-of-life as measured by the Paediatric Quality of Life (PedsQL) score
Mean change from baseline to Day 56, respectively in health-related quality-of-life as measured by the Paediatric Quality of Life (PedsQL) score. These multidimensional scales assess the frequency of health problems using generic and disease-specific approaches, respectively. Subjects and/or parent or proxies report a score of 0 to 4 (never to almost always) and questionnaires are tailored to age groups.
Time frame: Baseline - Day 56
Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient
Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator at baseline and Day 56. Evaluated on a 4-point scale as very efficient, good, fair or poor.
Time frame: Baseline - Day 56
Mean change in Myotonia Behaviour Scale (MBS) scores
Mean change from baseline to Day 56 in Myotonia Behaviour Scale (MBS) scores The Myotonia Behaviour Scale (MBS) (Hammaren et al., 2005) 0 No stiffness 1. Some stiffness exists, which can be ignored 2. Some stiffness exists, which can be ignored at times, but doesn't impair daily activities 3. Stiffness exists, which demands a higher level of mental awareness when performing some duties and activities 4. Severe stiffness exists, which impairs every duty and activity 5. Incapacitating stiffness exists, which demands constant moving not to be totally locked up, with regard to movement
Time frame: Baseline - Day 56
Changes in clinical laboratory values for laboratory safety assessments - Potassium
Changes in Potassium values from baseline to Day 56.
Time frame: Baseline - Day 56
Acceptability of the capsule formulation with respect to the swallowability.
Acceptability of the capsule formulation with respect to the swallowability. It will be assessed by interviewing patients and their caregivers at Day 56.
Time frame: Baseline - Day 56
Palatability of alternative administration
Palatability of alternative administration (capsule content with milk/juice or sprinkled on food) by 5-point facial hedonic scale correlated with 100-point Visual Analogue Scale (VAS) at each clinic visit
Time frame: Baseline - Day 56
Changes in clinical laboratory values from baseline to Day 56 for laboratory safety assessments - Changes in Magnesium values
Changes in Magnesium values from baseline to Day 56.
Time frame: Baseline - Day 56
Changes in clinical laboratory values from baseline to Day 56 for laboratory safety assessments - Changes in Sodium values
Changes in Sodium values from baseline to Day 56.
Time frame: Baseline - Day 56
Changes in clinical laboratory values from baseline to Day 56 for laboratory safety assessments - Changes in Calcium values
Changes in Calcium values from baseline to Day 56.
Time frame: Baseline - Day 56
Changes in clinical laboratory values from baseline to Day 56 for laboratory safety assessments - Changes in Chloride values
Changes in Chloride values from baseline to Day 56.
Time frame: Baseline - Day 56
Mean change in Faces scale for muscle pain, weakness and fatigue
A Faces (or other symbol) scale for children aged 6 to 8 years will be used to measure the score of muscle stiffness (myotonia severity). Faces scale will be used to assess pain, weakness and tiredness in study participants with a 10 cm straight horizontal line having the endpoints "no \[symptom\] at all" and "\[symptom\] as worst possible"
Time frame: Baseline - Day 56
This study is completed, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.
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Lupin Ltd.