E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Dystrophic Myotonia (NDM). Non-dystrophic myotonias are a group of rare neuromuscular disorders that cause episodes of muscle stiffness (known as myotonia) and paralysis. Predominantly the muscles of the face, hands and legs are affected. In addition to these episodes a permanent and debilitating muscle weakness can develop. The optimal treatment for these disorders is unknown. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10029317 |
E.1.2 | Term | Neuromuscular disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether mexiletine improves both quantitative and qualitative measures of myotnia (muscle stiffness) in patients with non-dystrophic myotonia. |
|
E.2.2 | Secondary objectives of the trial |
In addition the study will also allow investigators to examine specific NDM (non-dystrophic myotonia) subtype responses to therapy. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Age 18 years or older 2.Clinical symptoms or signs suggestive of myotonic disorders 3.Presence of myotonic potentials on electromyography (EMG) 4. Participation in the Non-Dystrophic Myotonia Natural History study; or a new patient with genetically confirmed NDM; or a new patient with a first degree relative (parent, sibling or child) with genetically confirmed NDM; or a new patient with clinical features of NDM in whom the mutation has not been localized, who areis DM1 and DM2 negative. 5.Patients on a stable dose of the following medications for 30 days prior to enrollment. Medications are: a.fibrate acid derivatives b.hydroxymethylglutaryl CoA reductase inhibitors 6. Practising an acceptable method of birth control for the duration of the trial, if a women of child bearing potential. |
|
E.4 | Principal exclusion criteria |
1.Inability or unwillingness to provide informed consent 2.Other neurological conditions that might affect the assessment of the study measurements 3.Genetic confirme DM1 (CTG>100 repeats) or DM2, if patient does not have genetically confirmed NDM. 4.Patients with existing cardiac conduction defects, evidence on EKG including but not limited to the following conditions: malignant arrhythmia or cardiac conduction disturbances (such as second degree AV block, third degree AV block, or prolonged QT interval >500ms or QRS duration >150 msec). 5.Current use of the following medication for a cardiac disorder: flecainide acetate, encainide, disopyramide, procainamide, quinine, propafenone or mexiletine. 6.Women who are pregnant or lactating 7. Patients currently on medications for myotonia such as phenytoin and flecainide acetate within 5 days of enrollment, carbamazepine and mexiletine within 3 days of enrollment, or acetazolamide, propafenone, procainamide, disopyramide, quinidine and encainide within 2 days of enrollment. 8. Patients with an existing permanent pacemaker. 9. Patients with renal or hepatic disease, heart failure, or seizures disorders. 10. Patients on medications that produce myotonia. This includes one or more of the following: a. chloroquine b. colchicines |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Patient-assessed symptoms: mean stiffness as measured by an Interactive Voice Response Diary (IVR) of daily calls made during weeks 2 and 3, and 7 and 8 of the trial. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial will be defined by the last visit of the last subject. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |