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Open-label Extension Study in Paediatric Patients Who Have Completed the MEX-NM-301 Study.

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ClinicalTrials.gov Identifier: NCT04622553
Recruitment Status : Not yet recruiting
First Posted : November 10, 2020
Last Update Posted : May 11, 2021
Sponsor:
Information provided by (Responsible Party):
Lupin Ltd.

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.

Condition or disease Intervention/treatment Phase
Myotonic Disorders Drug: Mexiletine Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Estimated Study Start Date : September 1, 2021
Estimated Primary Completion Date : November 1, 2023
Estimated Study Completion Date : February 6, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Cohort 1 and 2
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 pharmacokinetics (PK), safety and efficacy are confirmed in this population, of patients in Cohort 1

Other Name: Namuscla ™




Primary Outcome Measures :
  1. Assess the long-term safety and tolerability of mexiletine by AEs [ Time Frame: Approximately 24 months ]
    Assess the long-term safety and tolerability of mexiletine in paediatric patients by number and frequency of AEs/SAEs, throughout the study while on treatment

  2. Assess the long-term safety and tolerability of mexiletine by hand relaxation [ Time Frame: Approximately 24 months ]
    Mean time (in seconds) to relaxation of hand muscles and reduction in relaxation time from the first to the fifth contraction

  3. Assess the long-term safety and tolerability of mexiletine measurement of AESI [ Time Frame: Approximately 24 months ]
    Assess the long-term safety and tolerability of mexiletine in paediatric patients by Incidence of adverse events of special interest (AESI),

  4. Assess the long-term safety and tolerability of mexiletine by changes in ECG [ Time Frame: Approximately 24 months ]
    Assess the long-term safety and tolerability of mexiletine in paediatric patients by changes in ECG assessments from baseline, repeated at each study visit

  5. Assess the long-term safety and tolerability of mexiletine by muscle stiffness [ Time Frame: Approximately 24 months ]
    Score for muscle stiffness (myotonia severity) as self-reported by the patients on a Visual Analog Scale (VAS) or Faces scale


Secondary Outcome Measures :
  1. Mean change in VAS [ Time Frame: Approximately 24 months ]
    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 (every 3 months).

  2. Clinical myotonia assessment [ Time Frame: Approximately 24 months ]
    Mean change in time to open the eyes after forced eye closure as measured on a stopwatch (when eyelid myotonia present)

  3. Mean change in health-related quality-of-life [ Time Frame: Approximately 24 months ]
    Mean change in health-related quality-of-life as measured by the Paediatric Quality of Life (PedsQL) score (secondary endpoint for patients aged 6 years to <18 years; every 6 months).

  4. Clinical Global Impression (CGI) scores [ Time Frame: Approximately 24 months ]
    Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator. Measured every 6 months

  5. Mean change in Myotonia Behaviour Scale (MBS) scores [ Time Frame: Approximately 24 months ]
    Mean change in Myotonia Behaviour Scale (MBS) scores (for patients aged 6 years to < 18 years; measured every 6 months).

  6. Mean change in time to perform Timed-up and go (TUG) test [ Time Frame: Approximately 24 months ]
    Mean change in time to perform Timed-up and go (TUG) test (patients aged 6 to <18 years only)



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04622553


Contacts
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Contact: Nikki Adetoro 443-447-4534 NikkiAdetoro@lupin.com

Sponsors and Collaborators
Lupin Ltd.
Investigators
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Principal Investigator: Christine Barnérias, MD Hopital universitaire Necker-Enfants Malades
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Responsible Party: Lupin Ltd.
ClinicalTrials.gov Identifier: NCT04622553    
Other Study ID Numbers: MEX-NM-303
First Posted: November 10, 2020    Key Record Dates
Last Update Posted: May 11, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Myotonic Disorders
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Mexiletine
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action