<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02208050</url>
  </required_header>
  <id_info>
    <org_study_id>SVUHneuro002</org_study_id>
    <nct_id>NCT02208050</nct_id>
  </id_info>
  <brief_title>A Study of the Effectiveness of Fampridine in Improving Upper Limb Function in MS</brief_title>
  <official_title>A Phase IV Double Blind, Randomized, Placebo Controlled, Crossover Study of the Effectiveness of Oral Fampridine in Improving Upper Limb Function in Progressive Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College Dublin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University College Dublin</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine the effect of treatment with fampridine in patients&#xD;
      with secondary progressive MS (SPMS) or primary progressive MS (PPMS) with upper limb&#xD;
      dysfunction (as defined by a 9-HPT time of between 15-90 seconds) and Kurtzke EDSS scores in&#xD;
      the range 4.0-7.0 on upper limb function assessed by the nine-hole peg test (9-HPT) and the&#xD;
      Jebson Taylor Hand Function Test (JTT).&#xD;
&#xD;
      Fampridine has been shown to be effective in improving motor function, specifically walking&#xD;
      ability in prior studies in this patient population and is currently licensed for this use in&#xD;
      Europe and the United States. Upper limb dysfunction is common in SPMS and PPMS and often&#xD;
      underestimated. Fampridine effects action potential conduction in demyelinated nerve fibres&#xD;
      and we would hypothesise that the improvement previously reported in walking ability would be&#xD;
      similar to that on upper limb dysfunction. Our study aims to address this question using both&#xD;
      independent and patient reported outcomes in the context of a randomised placebo controlled&#xD;
      crossover trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND INFORMATION Patients with secondary progressive MS (SPMS) and primary progressive&#xD;
      MS (PPMS) have significant walking disability and impaired upper limb function due to&#xD;
      repeated demyelination and axonal injury affecting the corticospinal pathways. In some&#xD;
      patients this motor deficit may be predominantly due to demyelination resulting in motor&#xD;
      conduction slowing and/or block which is potentially reversible by blocking potassium&#xD;
      channels of demyelinated axons. Fampyra® (fampridine-PR) is a prolonged-release formulation&#xD;
      of the active drug substance 4-aminopyridine {4-AP; fampridine [International Nonproprietary&#xD;
      Name (INN)]. Fampridine is able to block certain voltage-gated K+ channels in neurons,&#xD;
      particularly in demyelinated nerves. Blockade of repolarising K+ currents can increase&#xD;
      synaptic transmission throughout the nervous system by increasing the duration of the&#xD;
      presynaptic action potential. Demyelinated nerves lose their ability to effectively conduct&#xD;
      action potentials and fampridine can help reverse this. This effect was demonstrated&#xD;
      clinically in a proportion of multiple sclerosis (MS) patients who showed a significant&#xD;
      improvement in motor function, specifically walking ability, with Fampyra treatment.&#xD;
      Fampridine-PR 10 mg every 12 hours or twice daily (BID) was approved in Europe (20 July 2011)&#xD;
      for this indication under the brand name of Fampyra®.&#xD;
&#xD;
      RATIONALE FOR THE STUDY Treatment with fampridine (4-aminopyridine), a potassium channel&#xD;
      blocker,1,2 has been shown to cause significant improvement in walking speed in one third of&#xD;
      MS patients with motor disability.3-5 In those patients who respond, approximately a 25%&#xD;
      improvement in walking speed was obtained with a self-reported 7 point improvement in the&#xD;
      Multiple Sclerosis Walking Scale (MSWS-12), a patient-rated measure of walking quality and&#xD;
      ability, 6,7 in comparison to non-responding patients and placebo control subjects.&#xD;
&#xD;
      Pharmacologically, the K+ channel blocking properties of fampridine and its effects on action&#xD;
      potential conduction in demyelinated nerve fiber preparations have been extensively&#xD;
      characterized. At low concentrations that are relevant to clinical experience (in the range&#xD;
      of 0.2 to 2 μM [18 to 180 ng/mL]), fampridine is able to block certain voltage-dependent K+&#xD;
      channels in neurons. It is this characteristic that appears to explain the ability of the&#xD;
      drug to restore conduction of action potentials in some critically demyelinated nerve fibers.&#xD;
      At higher (millimolar) concentrations, fampridine affects other types of K+ channels in both&#xD;
      neural and non-neural tissues. Blockade of repolarising K+ currents may increase synaptic&#xD;
      transmission throughout the nervous system by increasing the duration of the presynaptic&#xD;
      action potential. A range of neurological effects consistent with increased excitability of&#xD;
      nerve cells occurs with clinically relevant doses of fampridine.&#xD;
&#xD;
      The FDA has recently approved Fampridine, a slow release preparation, for use in the MS&#xD;
      patient population.8 It has also recently been approved in Europe (20th July 2011).17 Most&#xD;
      studies of fampridine assessed timed walking over twenty-five feet and the Multiple Sclerosis&#xD;
      Walking Scale-12 (MSWS-12).3-5 Deficits in arm and hand function are commonly found in&#xD;
      patients with SPMS and PPMS and can have an impact in performing many activities of daily&#xD;
      living. We propose to examine the efficacy of fampridine in upper limb function and in&#xD;
      overall disease impact in a single centre, double blind, randomized, placebo-controlled,&#xD;
      crossover study of patients attending St Vincent's University Hospital with significant&#xD;
      walking and upper limb disability due to SPMS and PPMS.&#xD;
&#xD;
      STUDY OBJECTIVE&#xD;
&#xD;
      The objective of this study is to assess the affect of PR-fampridine medication compared to&#xD;
      placebo for upper limb function in patients with progressive multiple sclerosis&#xD;
&#xD;
      TRIAL DESIGN&#xD;
&#xD;
      This will be a single centre, phase IV, double blind, randomized, placebo controlled,&#xD;
      crossover study on the effectiveness of oral Fampridine-PR 10mg tablets BID on upper limb&#xD;
      function for patients with progressive multiple sclerosis.&#xD;
&#xD;
      The trial will consist of a two week run in period followed by an eight week treatment period&#xD;
      were enrolled subjects will be randomised to receive either study drug or placebo in a double&#xD;
      blinded manner. This will be followed by a two-week wash out period followed by a further&#xD;
      eight-week study period using active drug or placebo. There will be a two-week washout period&#xD;
      at the end of the study. The total period of the study will be 22 weeks.&#xD;
&#xD;
      Each subject will attend for a screening visit and 8 assessment visits (total number of&#xD;
      visits, 9).&#xD;
&#xD;
      STUDY ASSESSMENTS AND PROCEDURES&#xD;
&#xD;
      Patients likely to fulfill the inclusion criteria and not meet any exclusion criteria will be&#xD;
      provided with information on the study and invited to attend a subsequent screening visit.&#xD;
      Only patients who have signed the informed consent form will participate in any study related&#xD;
      procedures including blood testing and ECG.&#xD;
&#xD;
      At screening visit (Assessment 1) subjects will have a physical examination and an expanded&#xD;
      disability status scale (EDSS) score rated. Blood samples will be taken for renal and liver&#xD;
      function and a baseline ECG performed. Patients will complete a nine-hole peg test (9-HPT)&#xD;
      and a Jebsen Taylor Hand Function Test (JTT). Timed 25 foot walk (T25FW) will be recorded and&#xD;
      the patients invited to complete the Multiple Sclerosis Impact Scale (MSIS-29), Multiple&#xD;
      Sclerosis Walking Scale (MSWS-12), Disabilities of the Arm, Shoulder and Hand (DASH) score,&#xD;
      Arm Function in Multiple Sclerosis Questionnaire (AMSQ) and SF-36 (quality of life)&#xD;
      questionnaire. Patients with any abnormalities on ECG, blood tests will not be invited to a&#xD;
      baseline visit and considered a screening failure.&#xD;
&#xD;
      Following screening visit subjects fulfilling the inclusion / exclusion criteria will have&#xD;
      two baseline visits (Assessments 2 and 3) at the end of week one and end of week two. The&#xD;
      9-HPT, JTT and T25FW will be repeated to allow for training effects. Patients will be&#xD;
      randomised to group A or group B and receive study medication or placebo at baseline visit&#xD;
      based on their blinded randomisation (Assessment 3).&#xD;
&#xD;
      The first treatment period will be from the start of week 3 until the end of week 10.&#xD;
      Patients will have an assessment at the end of week 6 (Assessment 4) and the end of week 10&#xD;
      (Assessment 5). At both assessments patients will have the 9-HPT, JTT, T25FW, MSIs-29,&#xD;
      MSWS-12, DASH, AMSQ and SF-36 recorded. Weeks 11 and 12 will be a washout period (no&#xD;
      drug/placebo). Assessment 6 will occur at the end of week 12 and will include recording of&#xD;
      9-HPT, JTT, T25FW, MSIs-29, MSWS-12, DASH, AMSQ and SF-36. Any adverse events will be&#xD;
      recorded at each visit as will the use of concomitant medications.&#xD;
&#xD;
      The second treatment period will begin at the start of week thirteen with groups A and B&#xD;
      switching study drug / placebo in a blinded manner. The second treatment period will continue&#xD;
      for a further 8 weeks with two more assessments ant week 16 (Assessment 7) and week 20&#xD;
      (Assessment 8). At both of these assessments subjects will complete the 9-HPT, JTT, T25FW,&#xD;
      MSIs-29, MSWS-12, DASH, AMSQ and SF-36. At the end of week 20 and EDSS score will be&#xD;
      recorded. Any adverse events will be recorded at each visit as will the use of concomitant&#xD;
      medications.&#xD;
&#xD;
      There will be a final washout period (weeks 21 and 22) after which a final visit (assessment&#xD;
      9) will occur and subjects once again completing 9-HPT, JTT, T25FW, MSIS-29, MSWS-12, DASH,&#xD;
      AMSQ and SF-36 and having n EDSS score recorded. Once again adverse events will be recorded.&#xD;
&#xD;
      Description of Study Assessments&#xD;
&#xD;
      Medical and Surgical History will be recorded with particular attention on the diagnosis of&#xD;
      MS, duration of MS and MS subtype.&#xD;
&#xD;
      Demographics The date of birth, gender and race will be recorded. Physical Examination The&#xD;
      complete physical examination will include the evaluation of the neurological system and a&#xD;
      recording of the EDSS score and T25FW.&#xD;
&#xD;
      ECG Test One ECG including a 12-lead examination will be performed at Screening (assessment&#xD;
      1).&#xD;
&#xD;
      Abnormal findings will be noted for clinical significance. The report will be signed by the&#xD;
      investigator.&#xD;
&#xD;
      Clinical Laboratory Tests&#xD;
&#xD;
        1. Haematology: haemoglobin, WBC, RBC, platelet count&#xD;
&#xD;
        2. Biochemistry: creatinine or creatinine-clearance, sodium, potassium, liver function&#xD;
           tests&#xD;
&#xD;
        3. All laboratory results will be reviewed and the reports signed by the investigator who&#xD;
           will record in the CRF whether they are normal, abnormal but not clinically significant,&#xD;
           or abnormal and clinically significant.&#xD;
&#xD;
      Pregnancy Tests Serum pregnancy test and urine pregnancy test in women of childbearing&#xD;
      potential will be performed.&#xD;
&#xD;
      Concomitant Medication In addition to Fampyra, any other treatments or procedures that are&#xD;
      considered necessary for the patient's welfare may be given at the discretion of the&#xD;
      Investigator. Administration of continuous concomitant procedures and medications (including&#xD;
      herbals and nutraceuticals) must be reported in the appropriate section of the CRF along with&#xD;
      reasons for use. Continuous concomitant procedures and medications are defined as a treatment&#xD;
      administered regularly for 2 weeks or more. The generic names for concomitant medications&#xD;
      should be recorded, if possible. The total daily dose should be recorded in the CRF whenever&#xD;
      possible. Concomitant use of medicinal products that are inhibitors of OCT2 for example,&#xD;
      cimetidine will be noted and will be deemed exclusion criteria. Concomitant use medicinal&#xD;
      products that are substrates of OCT2 for example, carvedilol, propanolol and metformin will&#xD;
      also be noted and the investigator will decide if the subject should successfully complete&#xD;
      screening.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 21, 2014</start_date>
  <completion_date type="Actual">February 16, 2016</completion_date>
  <primary_completion_date type="Actual">February 16, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT)</measure>
    <time_frame>20 weeks. Baseline assessments 1,2,3: weeks 0-2. Assessment 4 - midway through first treatment period; assessment 5: end of first treatment period. Assessment 7: midway through second treatment period, assessment 8: end of second treatment period.</time_frame>
    <description>9 Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs - this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. An upper limb responder is defined as a patient with both of the two &quot;on treatment&quot; 9 Hole Peg Test (9-HPT) assessments measured in seconds (assessments 4 &amp; 5 or 7 &amp; 8) improving 20% from the average of the baseline assessments (1, 2 &amp; 3). Washout assessment not included in the analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Defined as Upper Limb Responders on the Jebsen Taylor Hand Function Test (JTT)</measure>
    <time_frame>20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8</time_frame>
    <description>Jebsen Taylor Hand Function Test (JTT) is a timed test (seconds) comprising of seven 'real-world' tasks such as picking up small items. It has been validated for use in upper limb function in MS. A secondary measure of upper limb responsiveness will be defined as number of participants with a 20% improvement in from baseline in the average time taken to complete all seven tasks on the Jebsen Taylor Hand Function Test &quot;on treatment&quot; (assessments 4 &amp; 5 or 7 &amp; 8) compared with baseline assessments (assessments 1,2 &amp; 3).&#xD;
Baseline assessments (1,2,3) performed in two week period prior to first treatment block. Longer time indicates worse functioning. Improvement is defined as shorter time in seconds.&#xD;
Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Mobility Responders to Fampridine as Measured by an Improvement in the 25 Foot Timed Walk (T25FW)</measure>
    <time_frame>20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8</time_frame>
    <description>A mobility responder to Fampridine will be defined as a patient with both of the two &quot;on treatment&quot; T25FW assessments (assessments 4 &amp; 5 or 7 &amp; 8) being better (shorter time in seconds) than the maximum of any of the four &quot;off treatment&quot; assessments (assessments 1, 2, 3, 6). Otherwise the patient will be deemed a non-responder. T25FW test is the time taken to walk 25 feet taken as the average of two trials. Measured in seconds. Longer time indicates slower walking. Improvement is considered shorter amount of time in seconds - no specific percentage or amount of time was considered necessary.&#xD;
Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Scores in DASH - Fampridine and Placebo.</measure>
    <time_frame>20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.</time_frame>
    <description>Disabilities of the Arm Shoulder and Hand Scores questionnaire: The DASH consists of a 30-item disability symptom scale scored 0 (no disability) to 100, developed as a self-rated upper extremity disability and symptoms. Higher scores indicate higher self-perception of disability.&#xD;
DASH questionnaire administered to fampridine treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged. DASH questionnaire administered to placebo treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Scores in Multiple Sclerosis Walking Scale (MSWS-12) - Fampridine and Placebo.</measure>
    <time_frame>20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.</time_frame>
    <description>Multiple Sclerosis Walking Scale 12 is a 12-item self report measure of the impact of MS on an individual's walking ability. Scores are summed 1-3; 1-5 for each item. Higher scores indicate higher limitation in walking ability. Scores are summed and transformed to a 0-100 scale again with higher scores indicating higher self-reported limitation in walking ability. MSWS12 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. MSWS-12 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Scores in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Score Between Fampridine and Placebo.</measure>
    <time_frame>20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.</time_frame>
    <description>AMSQ - Arm Function in Multiple Sclerosis Questionnaire. This is a 31-item patient reported outcome measure which is validated to measure limitation in arm and hand functioning in people with multiple sclerosis. Patients rate the ability to which they can perform routine daily tasks with current hand function. Higher scores indicate greater limitations. Scale ranges from 0-100. AMSQ scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. AMSQ scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Scores of MSIS-29 - Fampridine and Placebo</measure>
    <time_frame>20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.</time_frame>
    <description>MSIS-29 is a patient reported outcome with a physical and psychological component combined into one scale. They refer to the self-reported impact of MS on their physical and psychological wellbeing. Higher scores indicate a higher impact on functioning. The 20 item physical scale and the 9 item psychological scale are reported as two separate scaled scores. Both scale ranges are 0-100. Higher scores indicate a higher impact on functioning. MSIS -20 and MSIS-9 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the scores was averaged. MMSIS-20 and MSIS-9 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the scores was averaged.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Secondary Progressive Multiple Sclerosis</condition>
  <condition>Primary Progressive Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients will be randomised to a 8 week treatment period with the active drug followed by a 2 week washout period before an 8 week treatment period with placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients will be randomised to a 8 week treatment period with the placebo, followed by a 2 week washout period and a further 8 week treatment period with the active drug.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fampridine</intervention_name>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Fampyra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must be able and willing to give written informed consent and to comply with&#xD;
             the requirements of this study protocol&#xD;
&#xD;
          -  Subjects must be diagnosed with clinically definite SPMS or PPMS and be judged to be&#xD;
             in generally good health by the investigator based upon the results of the medical&#xD;
             history, laboratory tests (liver and renal function), physical examination, 12-lead&#xD;
             electrocardiogram performed during Screening&#xD;
&#xD;
          -  Subjects must be Male or female aged 18-70 at baseline&#xD;
&#xD;
          -  Kurtzke EDSS scores in the range 4.0 to 7.0 inclusive&#xD;
&#xD;
          -  Evidence of significant upper limb dysfunction as defined by a 9HPT of 15 - 90 seconds&#xD;
             (dominant or non-dominant hand)&#xD;
&#xD;
          -  Female subjects with reproductive capabilities must have a negative serum pregnancy&#xD;
             test at baseline and agree to using an acceptable form of contraception for the&#xD;
             duration of the study (barrier, coil or oral contraceptives only).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy/sensitivity to study medications or their ingredients&#xD;
&#xD;
          -  Female subjects who are pregnant or breast-feeding or considering becoming pregnant&#xD;
             during the study.&#xD;
&#xD;
          -  Subjects unable to provide written informed consent&#xD;
&#xD;
          -  Subjects with a history of epilepsy or previous seizures (including provoked&#xD;
             seizures).&#xD;
&#xD;
          -  Subjects who have a history of drug or alcohol use that, in the opinion of the&#xD;
             investigator, would interfere with adherence to study requirements.&#xD;
&#xD;
          -  Subjects with an AST or ALT ≥ 3 x ULN on liver function tests&#xD;
&#xD;
          -  Subjects have clinically significant ECG findings as judged by the investigator, in&#xD;
             particular evidence of a cardiac conduction defect.&#xD;
&#xD;
          -  Significant upper or lower limb arthritis as considered by the investigator to&#xD;
             interfere with study assessments.&#xD;
&#xD;
          -  Significant cognitive impairment as considered by the investigator to interfere with&#xD;
             study assessments&#xD;
&#xD;
          -  Subjects with clinically significant upper limb ataxia considered by the investigator&#xD;
             to interfere with ability to complete study outcome measures.&#xD;
&#xD;
          -  Patients with mild, moderate or severe renal impairment (creatinine&#xD;
             clearance&lt;80ml/min) measured by 24-hour urine collection or estimated by the Cockcroft&#xD;
             and Gault formula&#xD;
&#xD;
          -  Subjects concomitantly using medicinal products that are inhibitors of Organic Cation&#xD;
             Transporter 2 (OCT2) for example cimetidine&#xD;
&#xD;
          -  Concurrent treatment with other medicinal products containing fampridine (4-&#xD;
             aminopyridine)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher McGuigan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University College Dublin, St Vincent's University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St Vincent's University Hospital</name>
      <address>
        <city>Dublin</city>
        <state>Dublin 4</state>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincents University Hospital</name>
      <address>
        <city>Dublin</city>
        <zip>D4</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>May 19, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <results_first_submitted>February 25, 2021</results_first_submitted>
  <results_first_submitted_qc>July 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 9, 2021</results_first_posted>
  <last_update_submitted>July 8, 2021</last_update_submitted>
  <last_update_submitted_qc>July 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University College Dublin</investigator_affiliation>
    <investigator_full_name>Christopher McGuigan</investigator_full_name>
    <investigator_title>Consultant Neurologist</investigator_title>
  </responsible_party>
  <keyword>Secondary Progressive Multiple Sclerosis</keyword>
  <keyword>Primary Progressive Multiple Sclerosis</keyword>
  <keyword>Multiple Sclerosis</keyword>
  <keyword>Upper limb function</keyword>
  <keyword>Mobility</keyword>
  <keyword>Fampridine</keyword>
  <keyword>DASH</keyword>
  <keyword>AMSQ</keyword>
  <keyword>MSWS-12</keyword>
  <keyword>MSIS-29</keyword>
  <keyword>SF-36</keyword>
  <keyword>9HPT</keyword>
  <keyword>25FTW</keyword>
  <keyword>JTT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Chronic Progressive</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>4-Aminopyridine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 3, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT02208050/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study recruited male and female patients between the ages of 18 - 70 years with clinically definite primary or secondary progressive multiple sclerosis, between 2013 and 2015. After recruitment and randomisation, three baseline assessments occurred over two weeks. Patients were then treated with fampridine-washout-placebo or placebo-washout-fampridine for 8 weeks followed by a 2 week washout and then cross-over to the other arm for 8 weeks followed by a 2 week washout.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Group A: Fampridine Followed by Placebo</title>
          <description>Participants who received fampridine first before crossing over to the placebo arm. Following baseline assessment and randomisation, participants received 10mg pr-fampridine twice daily for eight weeks followed by a two week washout period and then received placebo tablet twice daily for ten weeks.</description>
        </group>
        <group group_id="P2">
          <title>Group B: Placebo Followed by Fampridine</title>
          <description>Participants who received placebo first before crossing over to fampridine. After baseline assessment and randomisation, participants received placebo twice daily for 8 weeks, then had a 2 week washout period, followed by 8 weeks of treatment with 10mg pr-fampridine.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Baseline Assessment Period: 2 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treatment Period 1: 8 Weeks Treatment</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period 1: 2 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Treatment Period 2: 8 Weeks Treatment</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period 2: 2 Weeks Washout.</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group 1: Fampridine Followed by Placebo</title>
          <description>Patients will be randomised to a 8 week treatment period with the active drug followed by a 2 week washout period before an 8 week treatment period with placebo.&#xD;
Fampridine&#xD;
Placebo</description>
        </group>
        <group group_id="B2">
          <title>Group 2: Placebo Followed by Fampridine</title>
          <description>Patients will be randomised to a 8 week treatment period with the placebo, followed by a 2 week washout period and a further 8 week treatment period with the active drug.&#xD;
Fampridine&#xD;
Placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="36"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="64"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.1" lower_limit="45.1" upper_limit="59.5"/>
                    <measurement group_id="B2" value="53.7" lower_limit="45.4" upper_limit="60.9"/>
                    <measurement group_id="B3" value="55.1" lower_limit="45.4" upper_limit="60.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Sex</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Ireland</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Multiple Sclerosis (MS) Subtype</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Secondary Progressive MS (SPMS)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Primary Progressive MS (PPMS)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>On Disease Modifying Treatment (DMT)</title>
          <description>Participants who are currently being treated with a licensed disease modifying treatment (DMT) (not including symptomatic treatments) for multiple sclerosis including Interferons and Glatiramer Acetate.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EDSS (Expanded Disability Status Scale)</title>
          <description>Expanded Disability Status Scale is a measure designed to assess level of physical disability in multiple sclerosis, ranging from 0 - no detectable disability to 10 - death due to MS. Higher scores indicate higher levels of disability. Score of 6 indicates unilateral assistance required to mobilise, 6.5 indicates bilateral assistance required; 7 indicates predominantly using wheelchair.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6" lower_limit="4" upper_limit="7"/>
                    <measurement group_id="B2" value="6" lower_limit="4" upper_limit="7"/>
                    <measurement group_id="B3" value="6" lower_limit="4" upper_limit="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Duration</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15.7" lower_limit="9.9" upper_limit="24.6"/>
                    <measurement group_id="B2" value="19.2" lower_limit="9.0" upper_limit="25.4"/>
                    <measurement group_id="B3" value="16.8" lower_limit="9.3" upper_limit="25.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baclofen</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tizanadine</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Benzodiazepine</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="36"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT)</title>
        <description>9 Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs - this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. An upper limb responder is defined as a patient with both of the two &quot;on treatment&quot; 9 Hole Peg Test (9-HPT) assessments measured in seconds (assessments 4 &amp; 5 or 7 &amp; 8) improving 20% from the average of the baseline assessments (1, 2 &amp; 3). Washout assessment not included in the analysis.</description>
        <time_frame>20 weeks. Baseline assessments 1,2,3: weeks 0-2. Assessment 4 - midway through first treatment period; assessment 5: end of first treatment period. Assessment 7: midway through second treatment period, assessment 8: end of second treatment period.</time_frame>
        <population>Analysis population included all participants who received treatment and placebo for eight weeks. Two participants withdrew during the second 8-week treatment period and were not included in the final analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PR-Fampridine</title>
            <description>10mg fampridine twice daily for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo tablets twice daily for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT)</title>
          <description>9 Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs - this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. An upper limb responder is defined as a patient with both of the two &quot;on treatment&quot; 9 Hole Peg Test (9-HPT) assessments measured in seconds (assessments 4 &amp; 5 or 7 &amp; 8) improving 20% from the average of the baseline assessments (1, 2 &amp; 3). Washout assessment not included in the analysis.</description>
          <population>Analysis population included all participants who received treatment and placebo for eight weeks. Two participants withdrew during the second 8-week treatment period and were not included in the final analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dominant hand</title>
              <category_list>
                <category>
                  <title>Responders</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-responders</title>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-dominant hand</title>
              <category_list>
                <category>
                  <title>Responders</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-responders</title>
                  <measurement_list>
                    <measurement group_id="O1" value="60"/>
                    <measurement group_id="O2" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Defined as Upper Limb Responders on the Jebsen Taylor Hand Function Test (JTT)</title>
        <description>Jebsen Taylor Hand Function Test (JTT) is a timed test (seconds) comprising of seven 'real-world' tasks such as picking up small items. It has been validated for use in upper limb function in MS. A secondary measure of upper limb responsiveness will be defined as number of participants with a 20% improvement in from baseline in the average time taken to complete all seven tasks on the Jebsen Taylor Hand Function Test &quot;on treatment&quot; (assessments 4 &amp; 5 or 7 &amp; 8) compared with baseline assessments (assessments 1,2 &amp; 3).&#xD;
Baseline assessments (1,2,3) performed in two week period prior to first treatment block. Longer time indicates worse functioning. Improvement is defined as shorter time in seconds.&#xD;
Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period</description>
        <time_frame>20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8</time_frame>
        <population>Participants who had completed assessments at the above time points to allow analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Fampridine</title>
            <description>Fampridine 10mg bd treated participants in either Period 2 or Period 4.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo treated participants in Period 2 and Period 4.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Defined as Upper Limb Responders on the Jebsen Taylor Hand Function Test (JTT)</title>
          <description>Jebsen Taylor Hand Function Test (JTT) is a timed test (seconds) comprising of seven 'real-world' tasks such as picking up small items. It has been validated for use in upper limb function in MS. A secondary measure of upper limb responsiveness will be defined as number of participants with a 20% improvement in from baseline in the average time taken to complete all seven tasks on the Jebsen Taylor Hand Function Test &quot;on treatment&quot; (assessments 4 &amp; 5 or 7 &amp; 8) compared with baseline assessments (assessments 1,2 &amp; 3).&#xD;
Baseline assessments (1,2,3) performed in two week period prior to first treatment block. Longer time indicates worse functioning. Improvement is defined as shorter time in seconds.&#xD;
Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period</description>
          <population>Participants who had completed assessments at the above time points to allow analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dominant hand</title>
              <category_list>
                <category>
                  <title>Responders</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-responders</title>
                  <measurement_list>
                    <measurement group_id="O1" value="60"/>
                    <measurement group_id="O2" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-dominant hand</title>
              <category_list>
                <category>
                  <title>Responders</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non-responders</title>
                  <measurement_list>
                    <measurement group_id="O1" value="60"/>
                    <measurement group_id="O2" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Mobility Responders to Fampridine as Measured by an Improvement in the 25 Foot Timed Walk (T25FW)</title>
        <description>A mobility responder to Fampridine will be defined as a patient with both of the two &quot;on treatment&quot; T25FW assessments (assessments 4 &amp; 5 or 7 &amp; 8) being better (shorter time in seconds) than the maximum of any of the four &quot;off treatment&quot; assessments (assessments 1, 2, 3, 6). Otherwise the patient will be deemed a non-responder. T25FW test is the time taken to walk 25 feet taken as the average of two trials. Measured in seconds. Longer time indicates slower walking. Improvement is considered shorter amount of time in seconds - no specific percentage or amount of time was considered necessary.&#xD;
Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period.</description>
        <time_frame>20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8</time_frame>
        <population>Population with 25 foot walk data on analysis of results.</population>
        <group_list>
          <group group_id="O1">
            <title>Fampridine</title>
            <description>Fampridine 10mg BD for eight weeks with baseline assessment and washout period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo BD for eight weeks with baseline assessment and washout period.</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Mobility Responders to Fampridine as Measured by an Improvement in the 25 Foot Timed Walk (T25FW)</title>
          <description>A mobility responder to Fampridine will be defined as a patient with both of the two &quot;on treatment&quot; T25FW assessments (assessments 4 &amp; 5 or 7 &amp; 8) being better (shorter time in seconds) than the maximum of any of the four &quot;off treatment&quot; assessments (assessments 1, 2, 3, 6). Otherwise the patient will be deemed a non-responder. T25FW test is the time taken to walk 25 feet taken as the average of two trials. Measured in seconds. Longer time indicates slower walking. Improvement is considered shorter amount of time in seconds - no specific percentage or amount of time was considered necessary.&#xD;
Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period.</description>
          <population>Population with 25 foot walk data on analysis of results.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="61"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59"/>
                    <measurement group_id="O2" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-responders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Scores in DASH - Fampridine and Placebo.</title>
        <description>Disabilities of the Arm Shoulder and Hand Scores questionnaire: The DASH consists of a 30-item disability symptom scale scored 0 (no disability) to 100, developed as a self-rated upper extremity disability and symptoms. Higher scores indicate higher self-perception of disability.&#xD;
DASH questionnaire administered to fampridine treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged. DASH questionnaire administered to placebo treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged.</description>
        <time_frame>20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.</time_frame>
        <population>Mean scores in the DASH for all participants in the trial during on treatment periods (assessments 4&amp;5; 7&amp;8).</population>
        <group_list>
          <group group_id="O1">
            <title>Fampridine</title>
            <description>Average scores for participants treated with fampridine during weeks 2-10 or weeks 12-20.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Average scores for patients when treated with placebo during weeks 2-10 or weeks 12-20.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Scores in DASH - Fampridine and Placebo.</title>
          <description>Disabilities of the Arm Shoulder and Hand Scores questionnaire: The DASH consists of a 30-item disability symptom scale scored 0 (no disability) to 100, developed as a self-rated upper extremity disability and symptoms. Higher scores indicate higher self-perception of disability.&#xD;
DASH questionnaire administered to fampridine treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged. DASH questionnaire administered to placebo treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged.</description>
          <population>Mean scores in the DASH for all participants in the trial during on treatment periods (assessments 4&amp;5; 7&amp;8).</population>
          <units>Mean units on a scale.</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="63"/>
                <count group_id="O2" value="63"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.4" spread="19.5"/>
                    <measurement group_id="O2" value="38.3" spread="20.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Scores in Multiple Sclerosis Walking Scale (MSWS-12) - Fampridine and Placebo.</title>
        <description>Multiple Sclerosis Walking Scale 12 is a 12-item self report measure of the impact of MS on an individual's walking ability. Scores are summed 1-3; 1-5 for each item. Higher scores indicate higher limitation in walking ability. Scores are summed and transformed to a 0-100 scale again with higher scores indicating higher self-reported limitation in walking ability. MSWS12 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. MSWS-12 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.</description>
        <time_frame>20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.</time_frame>
        <population>Participants on treatment with Fampridine or Placebo.</population>
        <group_list>
          <group group_id="O1">
            <title>On Treatment: Fampridine</title>
            <description>Assessments during on-treatment periods with fampridine.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Assessments during on-treatment periods with Placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Scores in Multiple Sclerosis Walking Scale (MSWS-12) - Fampridine and Placebo.</title>
          <description>Multiple Sclerosis Walking Scale 12 is a 12-item self report measure of the impact of MS on an individual's walking ability. Scores are summed 1-3; 1-5 for each item. Higher scores indicate higher limitation in walking ability. Scores are summed and transformed to a 0-100 scale again with higher scores indicating higher self-reported limitation in walking ability. MSWS12 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. MSWS-12 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.</description>
          <population>Participants on treatment with Fampridine or Placebo.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.5" spread="28.2"/>
                    <measurement group_id="O2" value="65" spread="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Scores in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Score Between Fampridine and Placebo.</title>
        <description>AMSQ - Arm Function in Multiple Sclerosis Questionnaire. This is a 31-item patient reported outcome measure which is validated to measure limitation in arm and hand functioning in people with multiple sclerosis. Patients rate the ability to which they can perform routine daily tasks with current hand function. Higher scores indicate greater limitations. Scale ranges from 0-100. AMSQ scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. AMSQ scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.</description>
        <time_frame>20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.</time_frame>
        <population>Mean scores on AMSQ during on-treatment period. (AMSQ assessments 4 &amp; 5, 7 &amp; 8).</population>
        <group_list>
          <group group_id="O1">
            <title>Fampridine</title>
            <description>Assessments while participants on treatment with fampridine (4&amp;5 or 7&amp;8).</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Assessments while on treatment with placebo (4&amp;5 or 7&amp;8)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Scores in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Score Between Fampridine and Placebo.</title>
          <description>AMSQ - Arm Function in Multiple Sclerosis Questionnaire. This is a 31-item patient reported outcome measure which is validated to measure limitation in arm and hand functioning in people with multiple sclerosis. Patients rate the ability to which they can perform routine daily tasks with current hand function. Higher scores indicate greater limitations. Scale ranges from 0-100. AMSQ scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. AMSQ scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.</description>
          <population>Mean scores on AMSQ during on-treatment period. (AMSQ assessments 4 &amp; 5, 7 &amp; 8).</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.4" spread="19.8"/>
                    <measurement group_id="O2" value="38.4" spread="21.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Scores of MSIS-29 - Fampridine and Placebo</title>
        <description>MSIS-29 is a patient reported outcome with a physical and psychological component combined into one scale. They refer to the self-reported impact of MS on their physical and psychological wellbeing. Higher scores indicate a higher impact on functioning. The 20 item physical scale and the 9 item psychological scale are reported as two separate scaled scores. Both scale ranges are 0-100. Higher scores indicate a higher impact on functioning. MSIS -20 and MSIS-9 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the scores was averaged. MMSIS-20 and MSIS-9 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the scores was averaged.</description>
        <time_frame>20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.</time_frame>
        <population>Participants during on-treatment period with fampridine or placebo.</population>
        <group_list>
          <group group_id="O1">
            <title>Fampridine: MSIS-20</title>
            <description>MSIS-20 scores during treatment with fampridine.</description>
          </group>
          <group group_id="O2">
            <title>Placebo: MSIS20</title>
            <description>MSIS-20 scores during treatment with placebo.</description>
          </group>
          <group group_id="O3">
            <title>Fampridine: MSIS-9</title>
            <description>MSIS-9 scores during treatment with fampridine</description>
          </group>
          <group group_id="O4">
            <title>Placebo: MSIS-9</title>
            <description>MSIS-9 scores during treatment with placebo.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Scores of MSIS-29 - Fampridine and Placebo</title>
          <description>MSIS-29 is a patient reported outcome with a physical and psychological component combined into one scale. They refer to the self-reported impact of MS on their physical and psychological wellbeing. Higher scores indicate a higher impact on functioning. The 20 item physical scale and the 9 item psychological scale are reported as two separate scaled scores. Both scale ranges are 0-100. Higher scores indicate a higher impact on functioning. MSIS -20 and MSIS-9 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the scores was averaged. MMSIS-20 and MSIS-9 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the scores was averaged.</description>
          <population>Participants during on-treatment period with fampridine or placebo.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.4" spread="22"/>
                    <measurement group_id="O2" value="43.3" spread="24"/>
                    <measurement group_id="O3" value="30.5" spread="22"/>
                    <measurement group_id="O4" value="29.4" spread="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected for each participant for the study period (22 weeks).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Fampridine</title>
          <description>Adverse events reported by the patients when treated with Fampridine</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Adverse events reported by the patients when treated with placebo.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MeDRA 10.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Thrombocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Ear Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Lower Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Laceration to Foot</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Elevated hepatic enzymes</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Mobility</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Muscular pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Pain extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Hip Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Worsening hemiparesis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Muscle Spasticity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Numbness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="64"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral venous disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="64"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="64"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Professor Christopher McGuigan</name_or_title>
      <organization>St. Vincent's University Hospital</organization>
      <phone>+35312214209</phone>
      <email>C.McGuigan@svhg.ie</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02208050
org study id: SVUHneuro002
nct id: NCT02208050
lead sponsor: 
has dmc: Yes
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.
BACKGROUND INFORMATION Patients with secondary progressive MS (SPMS) and primary progressive
      MS (PPMS) have significant walking disability and impaired upper limb function due to
      repeated demyelination and axonal injury affecting the corticospinal pathways. In some
      patients this motor deficit may be predominantly due to demyelination resulting in motor
      conduction slowing and/or block which is potentially reversible by blocking potassium
      channels of demyelinated axons. Fampyra® (fampridine-PR) is a prolonged-release formulation
      of the active drug substance 4-aminopyridine {4-AP; fampridine [International Nonproprietary
      Name (INN)]. Fampridine is able to block certain voltage-gated K+ channels in neurons,
      particularly in demyelinated nerves. Blockade of repolarising K+ currents can increase
      synaptic transmission throughout the nervous system by increasing the duration of the
      presynaptic action potential. Demyelinated nerves lose their ability to effectively conduct
      action potentials and fampridine can help reverse this. This effect was demonstrated
      clinically in a proportion of multiple sclerosis (MS) patients who showed a significant
      improvement in motor function, specifically walking ability, with Fampyra treatment.
      Fampridine-PR 10 mg every 12 hours or twice daily (BID) was approved in Europe (20 July 2011)
      for this indication under the brand name of Fampyra®.

      RATIONALE FOR THE STUDY Treatment with fampridine (4-aminopyridine), a potassium channel
      blocker,1,2 has been shown to cause significant improvement in walking speed in one third of
      MS patients with motor disability.3-5 In those patients who respond, approximately a 25%
      improvement in walking speed was obtained with a self-reported 7 point improvement in the
      Multiple Sclerosis Walking Scale (MSWS-12), a patient-rated measure of walking quality and
      ability, 6,7 in comparison to non-responding patients and placebo control subjects.

      Pharmacologically, the K+ channel blocking properties of fampridine and its effects on action
      potential conduction in demyelinated nerve fiber preparations have been extensively
      characterized. At low concentrations that are relevant to clinical experience (in the range
      of 0.2 to 2 μM [18 to 180 ng/mL]), fampridine is able to block certain voltage-dependent K+
      channels in neurons. It is this characteristic that appears to explain the ability of the
      drug to restore conduction of action potentials in some critically demyelinated nerve fibers.
      At higher (millimolar) concentrations, fampridine affects other types of K+ channels in both
      neural and non-neural tissues. Blockade of repolarising K+ currents may increase synaptic
      transmission throughout the nervous system by increasing the duration of the presynaptic
      action potential. A range of neurological effects consistent with increased excitability of
      nerve cells occurs with clinically relevant doses of fampridine.

      The FDA has recently approved Fampridine, a slow release preparation, for use in the MS
      patient population.8 It has also recently been approved in Europe (20th July 2011).17 Most
      studies of fampridine assessed timed walking over twenty-five feet and the Multiple Sclerosis
      Walking Scale-12 (MSWS-12).3-5 Deficits in arm and hand function are commonly found in
      patients with SPMS and PPMS and can have an impact in performing many activities of daily
      living. We propose to examine the efficacy of fampridine in upper limb function and in
      overall disease impact in a single centre, double blind, randomized, placebo-controlled,
      crossover study of patients attending St Vincent's University Hospital with significant
      walking and upper limb disability due to SPMS and PPMS.

      STUDY OBJECTIVE

      The objective of this study is to assess the affect of PR-fampridine medication compared to
      placebo for upper limb function in patients with progressive multiple sclerosis

      TRIAL DESIGN

      This will be a single centre, phase IV, double blind, randomized, placebo controlled,
      crossover study on the effectiveness of oral Fampridine-PR 10mg tablets BID on upper limb
      function for patients with progressive multiple sclerosis.

      The trial will consist of a two week run in period followed by an eight week treatment period
      were enrolled subjects will be randomised to receive either study drug or placebo in a double
      blinded manner. This will be followed by a two-week wash out period followed by a further
      eight-week study period using active drug or placebo. There will be a two-week washout period
      at the end of the study. The total period of the study will be 22 weeks.

      Each subject will attend for a screening visit and 8 assessment visits (total number of
      visits, 9).

      STUDY ASSESSMENTS AND PROCEDURES

      Patients likely to fulfill the inclusion criteria and not meet any exclusion criteria will be
      provided with information on the study and invited to attend a subsequent screening visit.
      Only patients who have signed the informed consent form will participate in any study related
      procedures including blood testing and ECG.

      At screening visit (Assessment 1) subjects will have a physical examination and an expanded
      disability status scale (EDSS) score rated. Blood samples will be taken for renal and liver
      function and a baseline ECG performed. Patients will complete a nine-hole peg test (9-HPT)
      and a Jebsen Taylor Hand Function Test (JTT). Timed 25 foot walk (T25FW) will be recorded and
      the patients invited to complete the Multiple Sclerosis Impact Scale (MSIS-29), Multiple
      Sclerosis Walking Scale (MSWS-12), Disabilities of the Arm, Shoulder and Hand (DASH) score,
      Arm Function in Multiple Sclerosis Questionnaire (AMSQ) and SF-36 (quality of life)
      questionnaire. Patients with any abnormalities on ECG, blood tests will not be invited to a
      baseline visit and considered a screening failure.

      Following screening visit subjects fulfilling the inclusion / exclusion criteria will have
      two baseline visits (Assessments 2 and 3) at the end of week one and end of week two. The
      9-HPT, JTT and T25FW will be repeated to allow for training effects. Patients will be
      randomised to group A or group B and receive study medication or placebo at baseline visit
      based on their blinded randomisation (Assessment 3).

      The first treatment period will be from the start of week 3 until the end of week 10.
      Patients will have an assessment at the end of week 6 (Assessment 4) and the end of week 10
      (Assessment 5). At both assessments patients will have the 9-HPT, JTT, T25FW, MSIs-29,
      MSWS-12, DASH, AMSQ and SF-36 recorded. Weeks 11 and 12 will be a washout period (no
      drug/placebo). Assessment 6 will occur at the end of week 12 and will include recording of
      9-HPT, JTT, T25FW, MSIs-29, MSWS-12, DASH, AMSQ and SF-36. Any adverse events will be
      recorded at each visit as will the use of concomitant medications.

      The second treatment period will begin at the start of week thirteen with groups A and B
      switching study drug / placebo in a blinded manner. The second treatment period will continue
      for a further 8 weeks with two more assessments ant week 16 (Assessment 7) and week 20
      (Assessment 8). At both of these assessments subjects will complete the 9-HPT, JTT, T25FW,
      MSIs-29, MSWS-12, DASH, AMSQ and SF-36. At the end of week 20 and EDSS score will be
      recorded. Any adverse events will be recorded at each visit as will the use of concomitant
      medications.

      There will be a final washout period (weeks 21 and 22) after which a final visit (assessment
      9) will occur and subjects once again completing 9-HPT, JTT, T25FW, MSIS-29, MSWS-12, DASH,
      AMSQ and SF-36 and having n EDSS score recorded. Once again adverse events will be recorded.

      Description of Study Assessments

      Medical and Surgical History will be recorded with particular attention on the diagnosis of
      MS, duration of MS and MS subtype.

      Demographics The date of birth, gender and race will be recorded. Physical Examination The
      complete physical examination will include the evaluation of the neurological system and a
      recording of the EDSS score and T25FW.

      ECG Test One ECG including a 12-lead examination will be performed at Screening (assessment
      1).

      Abnormal findings will be noted for clinical significance. The report will be signed by the
      investigator.

      Clinical Laboratory Tests

        1. Haematology: haemoglobin, WBC, RBC, platelet count

        2. Biochemistry: creatinine or creatinine-clearance, sodium, potassium, liver function
           tests

        3. All laboratory results will be reviewed and the reports signed by the investigator who
           will record in the CRF whether they are normal, abnormal but not clinically significant,
           or abnormal and clinically significant.

      Pregnancy Tests Serum pregnancy test and urine pregnancy test in women of childbearing
      potential will be performed.

      Concomitant Medication In addition to Fampyra, any other treatments or procedures that are
      considered necessary for the patient's welfare may be given at the discretion of the
      Investigator. Administration of continuous concomitant procedures and medications (including
      herbals and nutraceuticals) must be reported in the appropriate section of the CRF along with
      reasons for use. Continuous concomitant procedures and medications are defined as a treatment
      administered regularly for 2 weeks or more. The generic names for concomitant medications
      should be recorded, if possible. The total daily dose should be recorded in the CRF whenever
      possible. Concomitant use of medicinal products that are inhibitors of OCT2 for example,
      cimetidine will be noted and will be deemed exclusion criteria. Concomitant use medicinal
      products that are substrates of OCT2 for example, carvedilol, propanolol and metformin will
      also be noted and the investigator will decide if the subject should successfully complete
      screening.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT)
time frame: 20 weeks. Baseline assessments 1,2,3: weeks 0-2. Assessment 4 - midway through first treatment period; assessment 5: end of first treatment period. Assessment 7: midway through second treatment period, assessment 8: end of second treatment period.
description: 9 Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs - this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. An upper limb responder is defined as a patient with both of the two "on treatment" 9 Hole Peg Test (9-HPT) assessments measured in seconds (assessments 4 & 5 or 7 & 8) improving 20% from the average of the baseline assessments (1, 2 & 3). Washout assessment not included in the analysis.
measure: Number of Participants Defined as Upper Limb Responders on the Jebsen Taylor Hand Function Test (JTT)
time frame: 20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8
description: Jebsen Taylor Hand Function Test (JTT) is a timed test (seconds) comprising of seven 'real-world' tasks such as picking up small items. It has been validated for use in upper limb function in MS. A secondary measure of upper limb responsiveness will be defined as number of participants with a 20% improvement in from baseline in the average time taken to complete all seven tasks on the Jebsen Taylor Hand Function Test "on treatment" (assessments 4 & 5 or 7 & 8) compared with baseline assessments (assessments 1,2 & 3).
Baseline assessments (1,2,3) performed in two week period prior to first treatment block. Longer time indicates worse functioning. Improvement is defined as shorter time in seconds.
Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period
measure: The Number of Mobility Responders to Fampridine as Measured by an Improvement in the 25 Foot Timed Walk (T25FW)
time frame: 20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8
description: A mobility responder to Fampridine will be defined as a patient with both of the two "on treatment" T25FW assessments (assessments 4 & 5 or 7 & 8) being better (shorter time in seconds) than the maximum of any of the four "off treatment" assessments (assessments 1, 2, 3, 6). Otherwise the patient will be deemed a non-responder. T25FW test is the time taken to walk 25 feet taken as the average of two trials. Measured in seconds. Longer time indicates slower walking. Improvement is considered shorter amount of time in seconds - no specific percentage or amount of time was considered necessary.
Assessment 4: Midway through first treatment period (week 4 of 8 week treatment period) Assessment 5: End of first treatment period (end of week 8) Assessment 7: Midway through second treatment period Assessment 8: End of second treatment period.
measure: Mean Scores in DASH - Fampridine and Placebo.
time frame: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.
description: Disabilities of the Arm Shoulder and Hand Scores questionnaire: The DASH consists of a 30-item disability symptom scale scored 0 (no disability) to 100, developed as a self-rated upper extremity disability and symptoms. Higher scores indicate higher self-perception of disability.
DASH questionnaire administered to fampridine treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged. DASH questionnaire administered to placebo treated group at Weeks 6,10,16 and 20. Scores at each time point were summed and averaged.
measure: Mean Scores in Multiple Sclerosis Walking Scale (MSWS-12) - Fampridine and Placebo.
time frame: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.
description: Multiple Sclerosis Walking Scale 12 is a 12-item self report measure of the impact of MS on an individual's walking ability. Scores are summed 1-3; 1-5 for each item. Higher scores indicate higher limitation in walking ability. Scores are summed and transformed to a 0-100 scale again with higher scores indicating higher self-reported limitation in walking ability. MSWS12 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. MSWS-12 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.
measure: Mean Scores in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Score Between Fampridine and Placebo.
time frame: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.
description: AMSQ - Arm Function in Multiple Sclerosis Questionnaire. This is a 31-item patient reported outcome measure which is validated to measure limitation in arm and hand functioning in people with multiple sclerosis. Patients rate the ability to which they can perform routine daily tasks with current hand function. Higher scores indicate greater limitations. Scale ranges from 0-100. AMSQ scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the 4 scores was averaged. AMSQ scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the 4 scores was averaged.
measure: Mean Scores of MSIS-29 - Fampridine and Placebo
time frame: 20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.
description: MSIS-29 is a patient reported outcome with a physical and psychological component combined into one scale. They refer to the self-reported impact of MS on their physical and psychological wellbeing. Higher scores indicate a higher impact on functioning. The 20 item physical scale and the 9 item psychological scale are reported as two separate scaled scores. Both scale ranges are 0-100. Higher scores indicate a higher impact on functioning. MSIS -20 and MSIS-9 scores were collected for the group on Placebo treatment at Weeks 6,10,16 and 20 - the sum of the scores was averaged. MMSIS-20 and MSIS-9 scores were collected for the group on Fampridine treatment at Weeks 6, 10, 16, 20. The sum of the scores was averaged.
arm group label: Group 1
arm group type: Other
description: Patients will be randomised to a 8 week treatment period with the active drug followed by a 2 week washout period before an 8 week treatment period with placebo.
arm group label: Group 2
arm group type: Other
description: Patients will be randomised to a 8 week treatment period with the placebo, followed by a 2 week washout period and a further 8 week treatment period with the active drug.
intervention type: Drug
intervention name: Fampridine
arm group label: Group 1
arm group label: Group 2
other name: Fampyra
intervention type: Drug
intervention name: Placebo
arm group label: Group 1
arm group label: Group 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Christopher McGuigan, MD
role: Principal Investigator
affiliation: University College Dublin, St Vincent's University Hospital
facility: 
facility: 
country: Ireland
responsible party type: Principal Investigator
investigator affiliation: University College Dublin
investigator full name: Christopher McGuigan
investigator title: Consultant Neurologist
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Chronic Progressive
mesh term: Sclerosis
mesh term: 4-Aminopyridine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 