A randomized, double-blind, placebo-controlled, cross-over study to assess the effects of fampridine on eye movements and nerve conduction and function in patients with multiple sclerosis (MS) and a unilateral or bilateral internuclear ophthalmoplegia (INO)

Phase 2

Completed

• Conditions: multiple sclerosis; nerve disease; 10012303

• Registration Number: NL-OMON42310
• Lead Sponsor: Centre for Human Drug Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

1. Male and female patients 18 years or more of age;
2. Diagnosis of multiple sclerosis according to the revised McDonald (2005) criteria;
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 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.

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 Cockroft-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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Eye movements at each day and time point. Variables will include (but not limit<br /><br>to):<br /><br>- eye position and velocity at the abducting/adducting eye<br /><br>-Versional disconjugacy index: the inter-ocular ratio of the peak velocity and<br /><br>peak acceleration of the abducting and adducting eye.<br /><br>-first-pass amplitude: the ratio of the position of the abducting eye to the<br /><br>adducting eye when both eyes reached their final position of ocular<br /><br>displacement with respect to the target position.<br /><br>- peak velocity ratio for each saccade<br /><br>- saccade pulse in the 2 eyes</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>A MRI-scan brain:<br /><br>- signal intensity MLF<br /><br>- length of MLF<br /><br><br /><br>Nerve conduction speed as determined by lag time of the adducting eye divided<br /><br>by the length of the MLF<br /><br><br /><br>Cognitive function test items from NeuroCart:<br /><br>- Adaptive tracking (motor-coordination)<br /><br>- Body sway (postural stability)<br /><br>- Rapid visual information processing (RVIP)<br /><br>- Simple reaction time task<br /><br>- Symbol Digit Substitution Test (SDST, cognitive processing speed)<br /><br>- Pharmaco-EEG<br /><br><br /><br>Pharmacokinetic endpoints: Tmax, Cmax, AUCinf, t1/2, Vd/f, CL/F<br /><br>Safety endpoints: Pulse, diastolic blood pressure, systolic blood pressure. </p><br>