A Study of the Effectiveness of Fampridine in Improving Upper Limb Function in MS
Condition: Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
Intervention: Fampridine; Placebo
Intervention MeSH terms: 4-Aminopyridine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis; Multiple Sclerosis; Upper limb function; Mobility; Fampridine; DASH; AMSQ; MSWS-12; MSIS-29; SF-36; 9HPT; 25FTW; JTT

Summary:

      The purpose of this study is to examine the effect of treatment with fampridine in patients
      with secondary progressive MS (SPMS) or primary progressive MS (PPMS) with upper limb
      dysfunction (as defined by a 9-HPT time of between 15-90 seconds) and Kurtzke EDSS scores in
      the range 4.0-7.0 on upper limb function assessed by the nine-hole peg test (9-HPT) and the
      Jebson Taylor Hand Function Test (JTT).

      Fampridine has been shown to be effective in improving motor function, specifically walking
      ability in prior studies in this patient population and is currently licensed for this use in
      Europe and the United States. Upper limb dysfunction is common in SPMS and PPMS and often
      underestimated. Fampridine effects action potential conduction in demyelinated nerve fibres
      and we would hypothesise that the improvement previously reported in walking ability would be
      similar to that on upper limb dysfunction. Our study aims to address this question using both
      independent and patient reported outcomes in the context of a randomised placebo controlled
      crossover trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be able and willing to give written informed consent and to comply with
             the requirements of this study protocol

          -  Subjects must be diagnosed with clinically definite SPMS or PPMS and be judged to be
             in generally good health by the investigator based upon the results of the medical
             history, laboratory tests (liver and renal function), physical examination, 12-lead
             electrocardiogram performed during Screening

          -  Subjects must be Male or female aged 18-70 at baseline

          -  Kurtzke EDSS scores in the range 4.0 to 7.0 inclusive

          -  Evidence of significant upper limb dysfunction as defined by a 9HPT of 15 - 90 seconds
             (dominant or non-dominant hand)

          -  Female subjects with reproductive capabilities must have a negative serum pregnancy
             test at baseline and agree to using an acceptable form of contraception for the
             duration of the study (barrier, coil or oral contraceptives only).

        Exclusion Criteria:

          -  Allergy/sensitivity to study medications or their ingredients

          -  Female subjects who are pregnant or breast-feeding or considering becoming pregnant
             during the study.

          -  Subjects unable to provide written informed consent

          -  Subjects with a history of epilepsy or previous seizures (including provoked
             seizures).

          -  Subjects who have a history of drug or alcohol use that, in the opinion of the
             investigator, would interfere with adherence to study requirements.

          -  Subjects with an AST or ALT ≥ 3 x ULN on liver function tests

          -  Subjects have clinically significant ECG findings as judged by the investigator, in
             particular evidence of a cardiac conduction defect.

          -  Significant upper or lower limb arthritis as considered by the investigator to
             interfere with study assessments.

          -  Significant cognitive impairment as considered by the investigator to interfere with
             study assessments

          -  Subjects with clinically significant upper limb ataxia considered by the investigator
             to interfere with ability to complete study outcome measures.

          -  Patients with mild, moderate or severe renal impairment (creatinine
             clearance<80ml/min) measured by 24-hour urine collection or estimated by the Cockcroft
             and Gault formula

          -  Subjects concomitantly using medicinal products that are inhibitors of Organic Cation
             Transporter 2 (OCT2) for example cimetidine

          -  Concurrent treatment with other medicinal products containing fampridine (4-
             aminopyridine)