Familial episodic ataxia (EA) represents a genetically and phenotypically diverse group of rare autosomal dominant hereditary disorders characterized by episodes of imbalance and incoordination that are variably associated with interictal neurological signs and typically triggered by physical exertion and emotional stress. Episodic ataxia type 2 (EA2) with associated interictal nystagmus and other ocular motor abnormalities is the most common and the best characterized of all EA syndromes. MedD
Conditions
Interventions
Trade Name: Fampyra TM
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: FAMPRIDINE
CAS Number: 504-24-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration nu
Sponsors
Hospital of the University of Munich, Grosshadern
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects will only be randomized in the study if they meet all of the following criteria: 1. Written informed consent of the subject 2. Patients (male or female) aged 18 years or older 3. Genetically confirmed episodic ataxia type 2 or a familial history of ataxia with clinical picture of episodic ataxia type 2 starting in childhood 4. Subjects, with the ability to follow study instructions and likely to attend and complete all required visits (Compliance) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects will not be randomized in the study if any of the following criteria applies: 1. Weight of 40 kg or less 2. Pregnancy or breast-feeding 3. Concurrend treatment with inhibitors of organic cation transporter 2 (OCT2), e.g. cimetidine 4. Known hypersensitivity to aminopyridine and/or acetazolamide/sulfonamide 5. Cardiovascular diseases e.g. recent heart attack (within the last 3 months), cardiac arrhythmia (QTc interval > 500 ms, atrial fibrillation, AV block grade = II), unstable angina pectoris, severe heart failure (NYHA class IV), severe arterial hypertension (grade III according to the guidelines of the German society of cardiology, 2008) 6. Recently occurred stroke (within the last 3 months) 7. Epileptic seizure currently or in the past 8. Asthma (severity = grade III) 9. Obstructive lung disease (e.g. pulmonary emphysema) 10. Liver insufficiency defined as GOT/GPT/total bilirubin > 3 x upper range (e.g. cirrhosis of the liver) 11. Milde or severe renal failure (Creatinine Clearance = 80ml/min) 12. Addison's disease 13. Unadjusted thyroid dysfunction 14. Acute gastric and intestinal ulcer 15. Known hyperchloremic acidosis 16. Depressed sodium and/or potassium blood serum levels 17. Chronic noncongestive glaucoma 18. Hypercalcaemia 19. Articular gout 20. Known African anaemia 21. Diabetes mellitus type I/II 22. Other acute, serious illness of the subject 23. Subject is unable to understand the scope, significance and consequences of this clinical trial and is unable to comply with the study design 24. Previous participation in this clinical trial or participation in any clinical trial taking an investigational medicinal product within 30 days prior to written informed consent for this clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: 1) Analysis of the efficacy of the two active IMPs (4-aminopyridine sustained-released, acetazolamide) regarding reduction of the frequency of attacks compared to placebo 2) Quantifying the differences between the two IMPs (4-aminopyridine sustained-released, acetazolamide) regarding reduction of the frequency of attacks ;Secondary Objective: Secondary objective: 1) Quantitative description and comparison of the median duration and intensity of attacks under 4-aminopyridine sustained-released vs. acetazolamide vs. placebo measured within the last 30 days of a 12-week treatment phase 2) Quantitative description and comparison of the gait variability at maximum walking speed at the end of a 12-week treatment phase under 4-aminopyridine sustained-released vs. acetazolamide vs. placebo 3) Analysis of the absolute change of the SARA scores and quality of life scores in the 3 treatment groups compared to the baseline score of each phase 4) Comparison of the frequency of (S)AEs under 4-aminopyridine sustained-released vs. acetazolamide vs. placebo;Primary end point(s): Primary endpoint: number of attacks within the last 30 days of each 12-week treatment phase ;Timepoint(s) of evaluation of this end point: 12 weeks after treatment with IMP (for each treatment phase) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint: 1) Median duration and intensity of the attacks within the last 30 days of each 12-week treatment phase 2) Change (relative change, log scale) of the gait variability (CV) at maximum walking speed measured at the end of a 12-week treatment phase (Visit 3, 6 and 9) as well as 4 weeks after taking the last IMP (follow-up visit) compared to the beginning of a 12-week tratment phase (Visit 1, 4 and 7) 3) Absolute change of VDADL and EQ-5D-5L (quality of life scores) measured at the end of a 12-week treatment phase (Visit 3, 6 and 9) as well as 4 weeks after taking the last IMP (follow-up visit) compared to the beginning of a12-week treatment phase (Visit 1, 4 and 7) 4) Absolute change of SARA scores measured at the end of a 12-week treatment phase (Visit 3, 6 and 9) as well as 4 weeks after taking the last IMP (follow-up visit) compared to the beginning of the respective 12-week treatment phase (Visit 1, 4 and 7);Timepoint(s) of evaluation of this end point: Regrading end point 1: At the beginning and 12 weeks after treatment with IMP (for each treatment phase) Regarding end point 2, 3 and 4: At the beginning and 12 weeks after treatment with IMP (for each treatment phase) as well as 4 weeks after taking the last IMP (follow-up) | — |
Countries
Germany
Contacts
Public ContactDSGZ
Hospital of the University of Munich
Outcome results
None listed