Multiple sclerosis (MS) and a unilateral or bilateral internuclear ophthalmoplegia (INO)
Conditions
Interventions
Trade Name: Fampyra 10 mg prolonged-release tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: FAMPRIDINE
CAS Number: 504-24-5
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
CHDR
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients 18 years or more of age; 2. Diagnosis of multiple sclerosis according to the revised McDonald criteria (Appendix A); 3. A disease duration > 1 year as defined by a diagnosis of MS at least one year prior to inclusion in the study; 4. Clinically stable disease > 30 days; 5. Subject shows evidence of INO for at least 30 days by quantitative neuro-ophthalmological criteria; 6. Subject is able to understand the demands of the protocol, has had any questions answered and has voluntarily signed the informed consent prior to any study procedures; and 7. Subject is otherwise in good health, based on complete medical history and physical examination, including blood pressure and pulse rate measurement, 12-lead ECG, and clinical laboratory tests. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Subject is a pregnant female (as determined by a urine pregnancy test), a lactating female, or a female of child-bearing potential, not sterilized and not using one of the following methods of birth control: oral or injectable contraceptive agent, implantable contraceptive device, or barrier method; 2. The neuro-ophthalmological examination demonstrates significant impairment of eye-movements due to cerebellar or other pathology which may infer with reliable testing of an INO; 3. Inability of a subject to maintain good visual fixation; 4. Subject has a prior history or current presentation of seizure; 5. Subject has a creatinine clearance less than 80 mL/min, calculated by Cocroft-Gault equation; 6. Subject has known allergy to fampridine; 7. Subject has any contraindication of MRI; 8. The subject has any medical condition, including psychiatric disease that might interfere with the interpretation of the results or with the conduct of the study; 9. Subject has a history of drug or ethanol abuse within the past year; 10. A positive urine drug screen; 11. Subject has a history of ischemic heart disease; 12. Concomitant use of fampridine with medicinal products that are inhibitors or substrates of organic cation transporter 2 (OCT2) such as cimetidine, carvedilol, propanolol and metformin; 13. Treatment with another investigational drug within 3 months prior to screening or having participated in more than 4 investigational drug studies within 1 year prior to screening; and/or 14. The subject has abnormal clinical laboratory values or an abnormal ECG, without approval of the study investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary endpoints Eye movements at each day and time point. Variables will include (but not limited to): - Eye position and velocity and the abducting/adducting eye - Peak velocity ratio for each saccade - Saccadic pulse in the 2 eyes - VDI (versional disconjugacy index) - FPA (first-pass amplitude);Timepoint(s) of evaluation of this end point: Eye movements at each day and time point: pre-dose (-1 h), 1.5 h, 2.5 h, 3.75 h and 5.5 h post-dose.;Main Objective: To evaluate the effects of fampridine on eye movements in patients with multiple sclerosis (MS) and a unilateral or bilateral internuclear ophthalmoplegia (INO);Secondary Objective: To evaluate the effects of fampridine on nerve conduction speed as determined through eye movement measurements and MRI scanning of the medial longitudinal fasciculus (MLF) in MS patients with a unilateral or bilateral INO To determine whether there is an association between MRI signal of the MLF and the nerve conduction velocity in MS patients with an INO To evaluate the pharmacodynamics effects of fampridine using the NeuroCart test battery To evaluate the pharmacokinetic (PK)-pharmacodynamic (PD) relationship for the effect of fampridine on nerve conduction in MS patients with an INO | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Brain MRI: screening Cognitive function test items from NeuroCart: pre-dose (-1 h), 3 h and 4.25 h post-dose. PK sampling will be performed at pre-dose (-1 h), 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5.5 h and 24 h post-dose.;Secondary end point(s): Secondary endpoints MRI brain: - Signal intensity MLF - Length of MLF Nerve conduction speed as determined by lag time of the adducting eye divided by the length of the MLF Cognitive function and neurophysiological test items from NeuroCart: - Adaptive tracking (motor-coordination) - Body sway (postural stability) - Rapid visual information processing (RVIP) - Simple reaction time task - Symbol Digit Substitution Test (SDST, cognitive processing speed) - Pharmaco-EEG Pharmacokinetic endpoints Plasma pharmacokinetic parameters of fampridine: Tmax, Cmax, AUCinf, t1/2, Vd/F, CL/F | — |
Countries
Netherlands
Contacts
Public ContactResearch Director
CHDR
Outcome results
None listed