An Observational Study in Adult Patients With Non-dystrophic Myotonic Disorders

An Observational Study to Describe the Long-term Safety and Effectiveness of Namuscla in the Symptomatic Management of Myotonia in Adult Patients With Non-dystrophic Myotonic Disorders

This is a non-interventional, prospective, observational, multicentre study to evaluate the long-term safety and effectiveness of Namuscla in adult patients with NDM.

Study Overview

• Status: Active, not recruiting
• Conditions: Myotonic Dystrophy
• Intervention / Treatment: Drug: Mexiletine

Detailed Description

This is a non-interventional, prospective, observational, multicentre study to evaluate the long-term safety and effectiveness of Namuscla in adult patients with NDM. Namuscla should be prescribed as per the approved Summary of Product Characteristics (SmPC).

Adult patients with non-dystrophic myotonic disorders who have been prescribed Namuscla by the treating physician, and who meet the eligibility criteria will be enrolled in this study.

This includes:

• Patients newly initiated on Namuscla for the treatment of NDM (newly exposed)
• Patients already on Namuscla/ mexiletine at enrolment - For patients receiving mexiletine other than Namuscla, only those who switch to Namuscla will be included in the study.

Patients already being treated with Namuscla/ mexiletine at the time of enrolment will be considered for enrolment provided they meet the eligibility criteria.

The study will be initiated at specialized centres for the treatment of myotonic disorders ("reference centres") in the United Kingdom (UK), France, and Germany, depending on availability of Namuscla in the specific country. Depending on the enrolment and marketing status (availability) of Namuscla in other countries in the EU, inclusion of additional sites in other countries will be considered.

The study population will comprise patients who are diagnosed with non-dystrophic myotonic disorders and considered suitable candidates for the treatment by Namuscla by the investigators according to the approved SmPC. Patients will be enrolled over an approximate 2-year enrolment period and will be followed-up on-treatment for up to 3 years. Each enrolled patient will be observed for 3 years or until discontinuation (if discontinued early).

For all enrolled patients, the baseline would be the latest data available at the enrolment visit.

For the patients already on Namuscla, cumulative data (data related previous exposure as well as current data) will be collected for adverse events (AEs) on Namuscla treatment.

No drug will be supplied for this study; patients will receive medicines through local standard practices. All evaluations and investigations during the study will be performed according to the routine clinical practices and discretion of the treating physician.

• Study Type: Observational
• Enrollment (Actual): 53

Contacts and Locations

• Study Contact: Name: Nikki Adetoro; Phone Number: 443-447-4534; Email: NikkiAdetoro@lupin.com

Study Locations

• France
  • Lille, France, 59000
    • CHRU Lille
  • Cedex
    • Paris, Cedex, France, 13 75013
      • Hôpital Universitaire de La Pitié Salpêtrière
• Germany
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm, Klinik für Neurologie
  • North-Rhine Westphalia
    • Bochum, North-Rhine Westphalia, Germany, 44791
      • St. Josef-Hospital Klinikum der Ruhr Universitaet Bochum
• United Kingdom
  • England
    • London, England, United Kingdom, WC1N 3BG
      • Institute of Neurology
    • Nottingham, England, United Kingdom, NG7 2UH
      • Nottingham University Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study will target the enrolment of 50 patients who are treated with Namuscla.

Description

Inclusion Criteria:

1. Adult, male or female patients with non-dystrophic myotonic disorders planned to be started on Namuscla according to the approved SmPC
2. Patients already receiving Namuscla/mexiletine for the treatment of NDM; (for patients on mexiletine other than Namuscla, only those who switch to Namuscla will be enrolled).
3. Patients who understand and are willing to provide informed consent.

Exclusion Criteria:

1. Patients who are enrolled or participating in any other clinical trial for an investigational product. -
2. Hypersensitivity to mexiletine, or to any of the excipients of Namuscla, or hypersensitivity to any local anaesthetic
3. Ventricular tachyarrhythmia
4. Atrial tachyarrhythmia, fibrillation or flutter
5. Complete heart block (ie, third-degree atrioventricular block) or any heart block susceptible to evolve to complete heart block (first-degree atrioventricular block with markedly prolonged PR interval (≥ 240 ms) and/or wide QRS complex (≥ 120 ms), second-degree atrioventricular block, bundle branch block, bifascicular and trifascicular block),
6. Myocardial infarction (acute or past), or abnormal Q-waves
7. Symptomatic coronary artery disease
8. Heart failure with reduced ejection fraction <50%
9. Sinus node dysfunction (including sinus rate < 50 bpm)
10. Patients receiving drugs that can induce torsades de pointes
11. Patients receiving medicinal products with narrow therapeutic index (ie, theophylline, tizanidine, digoxin, lithium, phenytoin or warfarin)
12. Patients who are pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome 1 Proportion of patients with treatment-emergent AEs	Proportion of patients with treatment-emergent AEs ([TEAEs], including SAEs) from study enrolment to 6, 12, 24 and 36 months on Namuscla	Approximately 3 years
Primary Outcome 2 Proportion of patients requiring dose reduction or treatment discontinuation	Proportion of patients requiring dose reduction or treatment discontinuation due to AEs (including SAEs).	Approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Outcome Proportion of patients with AEs /SAEs/ Adverse Event of Special Interest (AESI)	Proportion of patients with AEs /SAEs/ Adverse Event of Special Interest (AESI) from study enrolment to 6, 12, 24, and 36 months	Approximately 3 years

Collaborators and Investigators

• Sponsor: Lupin Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2020
• Primary Completion (Anticipated): November 19, 2025
• Study Completion (Anticipated): February 24, 2026

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: November 4, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Muscular Disorders, Atrophic; Heredodegenerative Disorders, Nervous System; Muscular Dystrophies; Myotonic Dystrophy; Myotonic Disorders; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Membrane Transport Modulators; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Mexiletine
• Other Study ID Numbers: LUP/MEX/2018/001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No