Clinical trial NCT04622553: Open-label Extension Study in Paediatric Patients Who Have Completed the MEX-NM-301 Study.
Official title: Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of Mexiletine in Paediatric Patients With Myotonic Disorders Who Have Completed the MEX-NM-301 Study.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Myotonic Disorders
Lead sponsor: Lupin Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-10
Enrollment: 14
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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 study MEX-NM-301.
Primary purpose: TREATMENT

Brief summary: Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of Mexiletine in Paediatric Patients with Myotonic Disorders Who Have Completed the MEX-NM-301 study.

Detailed description: This is an open-label extension study evaluating the long-term efficacy and safety of mexiletine in paediatric patients with myotonic disorders who have completed the initial parent paediatric study with mexiletine (Protocol No. MEX-NM-301 (PIP Study 4) for children and adolescents aged 6 to \< 18 years and who continue to meet the eligibility criteria.

Patients who meet the eligibility criteria and provide consent for this study will be enrolled sequentially by decreasing age groups. Patients aged 12 to \< 18 years will enter first as this is the first cohort expected to complete the parent study PIP Study 4 based on top down recruiting. Once initial pharmacokinetics (PK), safety and efficacy are confirmed in this population, patients aged 6 to \<12 years will be first enrolled in PIP Study 4 and subsequently this study (PIP Study 7).

Enrolled patients will receive mexiletine at a dose determined in the parent study. Dosing is determined according to body weight and tolerability.

The study includes 9 clinic visits - V1 (baseline), and V2 to V9 every 3 months, approximately, thereafter.

The total duration of study will be 24 months per patient. End-of-treatment (EOT) visit will occur at 24 months or in accordance with the availability of product. The overall study duration would be approximately 5 years.

Eligibility criteria: Inclusion Criteria:

1. Patients previously completed the parent study PIP study 4 (MEX-NM-301) and tolerated the Mexiletine in the study.
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.
3. Patients continue to meet inclusion criteria of parent study (MEX-NM-301):

   * No significant cardiac abnormalities as determined by a cardiologist's assessment of the ECG and Echocardiogram
   * No history or evidence of any significant liver disorder Laboratory investigations for haematology, biochemistry, and urinalysis at screening are within normal range, or showing no clinically relevant abnormal values, as judged by the Investigator
   * 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 or have a vasectomized partner or are practicing abstinence

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 described in the Namuscla Summary of Product Characteristics \[SmPC\])

   * Hypersensitivity to the active substance, or to any of the excipients
   * Hypersensitivity to any local anaesthetic
   * Ventricular tachyarrhythmia
   * 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),
   * QT interval \> 450ms
   * Myocardial infarction (acute or past), or abnormal Q-waves
   * Symptomatic coronary artery disease
   * Heart failure with ejection fraction \<50%
   * Atrial tachyarrhythmia, fibrillation or flutter
   * Sinus node dysfunction (including sinus rate \< 50 bpm)
   * Co-administration with medicinal products inducing torsades de pointes (class Ia, Ic, III antiarrhythmics): Co-administration of mexiletine and antiarrhythmics inducing torsades de pointes (class Ia: quinidine, procainamide, disopyramide, ajmaline; class Ic: encainide, flecainide, propafenone, moricizine; class III: amiodarone, sotalol, ibutilide, dofetilide, dronedarone, vernakalant) increases the risk of potentially lethal torsades de pointes.
   * 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.

Primary outcomes:
measure: Assess the long-term safety and tolerability of mexiletine by AEs
timeFrame: Approximately 24 months
measure: Assess the long-term safety and tolerability of mexiletine by hand relaxation
timeFrame: Approximately 24 months
measure: Assess the long-term safety and tolerability of mexiletine measurement of AESI
timeFrame: Approximately 24 months
measure: Assess the long-term safety and tolerability of mexiletine by changes in ECG
timeFrame: Approximately 24 months
measure: Assess the long-term safety and tolerability of mexiletine by muscle stiffness
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Mean change in VAS
timeFrame: Approximately 24 months
measure: Clinical myotonia assessment
timeFrame: Approximately 24 months
measure: Mean change in health-related quality-of-life
timeFrame: Approximately 24 months
measure: Clinical Global Impression (CGI) scores
timeFrame: Approximately 24 months
measure: Mean change in Myotonia Behaviour Scale (MBS) scores
timeFrame: Approximately 24 months
measure: Mean change in time to perform Timed-up and go (TUG) test
timeFrame: Approximately 24 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants-Malades
Study officials:
affiliation: Hopital universitaire Necker-Enfants Malades
name: Christine Barnérias, MD
role: PRINCIPAL_INVESTIGATOR
References: