<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/NCT02967679</url>
  </required_header>
  <id_info>
    <org_study_id>MD1003CT2015-01 SERENDEM</org_study_id>
    <nct_id>NCT02967679</nct_id>
  </id_info>
  <brief_title>SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study</brief_title>
  <official_title>SERENDEM Study: MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MedDay Pharmaceuticals SA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MedDay Pharmaceuticals SA</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The single-center, open-label Phase II study has the objective of assess the effect of MD1003&#xD;
      on motor and sensory conduction in patients suffering from demyelinating polyneuropathies in&#xD;
      15 subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 5, 2016</start_date>
  <completion_date type="Actual">March 18, 2019</completion_date>
  <primary_completion_date type="Actual">March 18, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Motor Nerve Conduction Velocity (m/Sec)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Absolute change from baseline at Week 48.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Distal Latency (Msec)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Absolute change from baseline at Week 48.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>F Wave Latency (Msec)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Absolute change from baseline at Week 48.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Length of Motor Nerve Potential</measure>
    <time_frame>48 weeks</time_frame>
    <description>Absolute change from baseline at W48.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ONLS (Overall Neuropathy Limitations Scale)</measure>
    <time_frame>48 weeks</time_frame>
    <description>The ONLS focuses on upper and lower limb functions, and consists of a checklist for interviewing patients. It is scored from 0 to 5 on the upper limb section and from 0 to 7 on the lower limb section. A score of 0 indicates no limitations (the ceiling of the scale) and a score of 5 or 7 indicates no purposeful movement. Absolute change from baseline at week 48.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline at Week 48 for Timed 10-meter Walk Test</measure>
    <time_frame>48 weeks</time_frame>
    <description>Absolute change from baseline at week 48. The patient is instructed to walk at normal pace for 10 meters. Start and stop of performance time coincides with the toes of the leading foot crossing the 2-m mark and the 8-m mark, respectively. From these data, the speed may be calculated by dividing the middle 6 m by the time (in seconds).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Change From Baseline at Week 48 for Medical Research Council (MRC) Subscore (Total Muscle) and Total Score</measure>
    <time_frame>48 weeks</time_frame>
    <description>MRC score assessed in 19 muscles.&#xD;
The muscle scale grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle.&#xD;
The patient's effort is graded on a scale of 0-5:&#xD;
Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.&#xD;
Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed. As an example, the elbow can be moved from full extension to full flexion starting with the arm hanging down at the side.&#xD;
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.&#xD;
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.&#xD;
Grade 0: No movement is observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>INCAT Sensory Sum Score (ISS)</measure>
    <time_frame>48 weeks</time_frame>
    <description>This sensory scale comprises pin prick and vibration sense plus a two point discrimination value in the arms and legs, and ranges from 0 (&quot;normal sensation&quot;) to 20 (&quot;most severe sensory deficit&quot;). Absolute change from baseline at week 48.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-minute Walk Test</measure>
    <time_frame>48 weeks</time_frame>
    <description>The 6MWT is a practical simple test that requires a 30 m (100-ft) hallway. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. Absolute change from baseline at week 48.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Posturography Score</measure>
    <time_frame>48 weeks</time_frame>
    <description>Computerized dynamic posturography (CDP) is a non-invasive specialized clinical assessment technique used to quantify the central nervous system adaptive mechanisms (sensory, motor and central) involved in the control of posture and balance, both in normal and abnormal conditions. Absolute change of speed in spontaneous speed condition from baseline at week 48.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Excitability Testing: Supernormality (%)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Nerve excitability testing is a non-invasive approach in investigating the pathophysiology of peripheral nerve disorders, which determines the electrical properties of the nerve membrane at the site of stimulation. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). During the 10-30 ms following the end of the refractory period, the axon increases its excitability and the nerve fiber is more easily excited (the supernormal period). Depolarization of the node of Ranvier excites the adjacent internodes, which then charge with electric current as capacitors. Supernormality depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Strength-duration Time Constant (ms)</measure>
    <time_frame>48 weeks</time_frame>
    <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
Strength-duration Time Constant (ms) is a measurement of excitability, defined as the duration of the stimulus that has twice the strength of the rheobase current (see below). The lower the rheobase is, the higher is the Strenght duration time constant. Accordingly, higer values of SDTC are associated with better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rheobase (mA)</measure>
    <time_frame>48 weeks</time_frame>
    <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
Rheobase is the minimal strength of an electrical stimulus of infinitely long duration that is able to cause excitation. Low values are associated with better outcome (the nerve becomes more excitable).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Refractoriness (%)</measure>
    <time_frame>48 weeks</time_frame>
    <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline to week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Absolute Refractory Period (ms).</measure>
    <time_frame>48 weeks</time_frame>
    <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Absolute Refractory Period (ms).</measure>
    <time_frame>Week 48</time_frame>
    <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Chronic Inflammatory Demyelinating Polyneuropathy</condition>
  <condition>Peripheral Neuropathy</condition>
  <condition>Charcot-Marie-Tooth Disease</condition>
  <condition>Charcot-Marie-Tooth Disease Type 1A</condition>
  <condition>Charcot-Marie-Tooth Disease, Type 1B</condition>
  <condition>Anti-MAG Neuropathy</condition>
  <arm_group>
    <arm_group_label>MD1003</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MD1003</intervention_name>
    <arm_group_label>MD1003</arm_group_label>
    <other_name>High Dose Biotin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female aged between 20 and 85 years.&#xD;
&#xD;
          -  Patients fulfilling one of the following diagnosis:&#xD;
&#xD;
          -  Five patients with chronic inflammatory demyelinating polyneuropathy on both clinical&#xD;
             and neurophysiological grounds.&#xD;
&#xD;
          -  Five patients with proven genetic diagnosis of CMT1a or CMT1b&#xD;
&#xD;
          -  Five patients with anti-MAG polyneuropathy.&#xD;
&#xD;
          -  Electrophysiological parameters worsening for the past 3 years&#xD;
&#xD;
          -  Available EMG record, performed during the past 6 months to assess variability of NCV&#xD;
             parameters&#xD;
&#xD;
          -  Signed and dated written informed consent to participate in the study in accordance&#xD;
             with local regulations&#xD;
&#xD;
          -  Likely to be able to participate in all scheduled evaluation and complete all required&#xD;
             study procedures,&#xD;
&#xD;
          -  In the opinion of the investigator, the patient will be compliant and have a high&#xD;
             probability of completing the study.&#xD;
&#xD;
          -  Both male and female subjects who are not either surgically sterile (tubal&#xD;
             ligation/obstruction or removal of ovaries or uterus) or post-menopausal (no&#xD;
             spontaneous menstrual periods for at least one year confirmed by a negative hormone&#xD;
             panel) must commit to using TWO highly effective method of birth control for the&#xD;
             duration of the study and for two months after the treatment termination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any general chronic handicapping disease other than peripheral neuropathy&#xD;
&#xD;
          -  Impossibility to perform the 10 meters walking test&#xD;
&#xD;
          -  Impossibility to assess electrophysiological parameters&#xD;
&#xD;
          -  Patients with uncontrolled hepatic disorder, renal or cardiovascular disease, or&#xD;
             cancer,&#xD;
&#xD;
          -  Patients with hypersensitivity to MD1003 excipients (lactose)&#xD;
&#xD;
          -  Laboratory tests out of normal range according to the reference laboratory values.&#xD;
             Deviations may be accepted if considered by the investigator as not clinically&#xD;
             significant with regards to the study continuation,&#xD;
&#xD;
          -  Patients with history or presence of alcohol abuse or drug addiction,&#xD;
&#xD;
          -  Patients likely to be non-compliant to the study procedures or for whom a long-term&#xD;
             follow-up seems to be difficult to achieve.&#xD;
&#xD;
          -  Any new medication for neuropathy initiated less than 3 months prior to inclusion. For&#xD;
             CIDP patients, relapse in the past 3 months before inclusion.&#xD;
&#xD;
          -  Not easily contactable by the investigator in case of emergency or not capable to call&#xD;
             the investigator&#xD;
&#xD;
          -  Subjects without effective contraception&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alain CREANGE, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Henri Mondor, Créteil, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Frederic Sedel, MD</last_name>
    <role>Study Director</role>
    <affiliation>Medday Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Henri Mondor, Créteil, France</name>
      <address>
        <city>Creteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <link>
    <url>http://www.medday-pharma.com</url>
    <description>Sponsor</description>
  </link>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>November 8, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <results_first_submitted>September 21, 2020</results_first_submitted>
  <results_first_submitted_qc>October 29, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 2, 2020</results_first_posted>
  <last_update_submitted>October 29, 2020</last_update_submitted>
  <last_update_submitted_qc>October 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neuropathy</keyword>
  <keyword>Demyelinating polyradiculoneuropathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tooth Diseases</mesh_term>
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
    <mesh_term>Polyneuropathies</mesh_term>
    <mesh_term>Charcot-Marie-Tooth Disease</mesh_term>
    <mesh_term>Nerve Compression Syndromes</mesh_term>
    <mesh_term>Hereditary Sensory and Motor Neuropathy</mesh_term>
    <mesh_term>Polyradiculoneuropathy, Chronic Inflammatory Demyelinating</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Biotin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT02967679/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT02967679/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>MD1003</title>
          <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Five patients with chronic inflammatory demyelinating polyneuropathy on both clinical and neurophysiological grounds.&#xD;
Five patients with proven genetic diagnosis of CMT1a or CMT1b&#xD;
Five patients with anti-MAG polyneuropathy.</population>
      <group_list>
        <group group_id="B1">
          <title>MD1003</title>
          <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.36" spread="14.07"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </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_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>France</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease type</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>CIDP patients</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CMT1a or CMT1b patients</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>anti-MAG polyneuropathy</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Motor Nerve Conduction Velocity (m/Sec)</title>
        <description>Absolute change from baseline at Week 48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Motor Nerve Conduction Velocity (m/Sec)</title>
          <description>Absolute change from baseline at Week 48.</description>
          <units>m/s</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.67" spread="11.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.7615</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.67</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>11.45</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Distal Latency (Msec)</title>
        <description>Absolute change from baseline at Week 48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Distal Latency (Msec)</title>
          <description>Absolute change from baseline at Week 48.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" spread="8.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.5995</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.20</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>8.89</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>F Wave Latency (Msec)</title>
        <description>Absolute change from baseline at Week 48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>F Wave Latency (Msec)</title>
          <description>Absolute change from baseline at Week 48.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="8.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.1641</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>4.8</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>8.40</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Length of Motor Nerve Potential</title>
        <description>Absolute change from baseline at W48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Motor Nerve Potential</title>
          <description>Absolute change from baseline at W48.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.5" spread="16.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0353</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>8.5</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>16.5</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ONLS (Overall Neuropathy Limitations Scale)</title>
        <description>The ONLS focuses on upper and lower limb functions, and consists of a checklist for interviewing patients. It is scored from 0 to 5 on the upper limb section and from 0 to 7 on the lower limb section. A score of 0 indicates no limitations (the ceiling of the scale) and a score of 5 or 7 indicates no purposeful movement. Absolute change from baseline at week 48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>ONLS (Overall Neuropathy Limitations Scale)</title>
          <description>The ONLS focuses on upper and lower limb functions, and consists of a checklist for interviewing patients. It is scored from 0 to 5 on the upper limb section and from 0 to 7 on the lower limb section. A score of 0 indicates no limitations (the ceiling of the scale) and a score of 5 or 7 indicates no purposeful movement. Absolute change from baseline at week 48.</description>
          <units>score 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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.2642</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.5</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>1.4</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline at Week 48 for Timed 10-meter Walk Test</title>
        <description>Absolute change from baseline at week 48. The patient is instructed to walk at normal pace for 10 meters. Start and stop of performance time coincides with the toes of the leading foot crossing the 2-m mark and the 8-m mark, respectively. From these data, the speed may be calculated by dividing the middle 6 m by the time (in seconds).</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline at Week 48 for Timed 10-meter Walk Test</title>
          <description>Absolute change from baseline at week 48. The patient is instructed to walk at normal pace for 10 meters. Start and stop of performance time coincides with the toes of the leading foot crossing the 2-m mark and the 8-m mark, respectively. From these data, the speed may be calculated by dividing the middle 6 m by the time (in seconds).</description>
          <units>second</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.1777</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.6</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>1.2</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Change From Baseline at Week 48 for Medical Research Council (MRC) Subscore (Total Muscle) and Total Score</title>
        <description>MRC score assessed in 19 muscles.&#xD;
The muscle scale grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle.&#xD;
The patient's effort is graded on a scale of 0-5:&#xD;
Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.&#xD;
Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed. As an example, the elbow can be moved from full extension to full flexion starting with the arm hanging down at the side.&#xD;
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.&#xD;
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.&#xD;
Grade 0: No movement is observed.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Change From Baseline at Week 48 for Medical Research Council (MRC) Subscore (Total Muscle) and Total Score</title>
          <description>MRC score assessed in 19 muscles.&#xD;
The muscle scale grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle.&#xD;
The patient's effort is graded on a scale of 0-5:&#xD;
Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.&#xD;
Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed. As an example, the elbow can be moved from full extension to full flexion starting with the arm hanging down at the side.&#xD;
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.&#xD;
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.&#xD;
Grade 0: No movement is observed.</description>
          <units>score 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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="8.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0371</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>4.5</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>8.2</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>INCAT Sensory Sum Score (ISS)</title>
        <description>This sensory scale comprises pin prick and vibration sense plus a two point discrimination value in the arms and legs, and ranges from 0 (&quot;normal sensation&quot;) to 20 (&quot;most severe sensory deficit&quot;). Absolute change from baseline at week 48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>INCAT Sensory Sum Score (ISS)</title>
          <description>This sensory scale comprises pin prick and vibration sense plus a two point discrimination value in the arms and legs, and ranges from 0 (&quot;normal sensation&quot;) to 20 (&quot;most severe sensory deficit&quot;). Absolute change from baseline at week 48.</description>
          <units>score 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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.2" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0142</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-2.2</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>2.9</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>6-minute Walk Test</title>
        <description>The 6MWT is a practical simple test that requires a 30 m (100-ft) hallway. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. Absolute change from baseline at week 48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>6-minute Walk Test</title>
          <description>The 6MWT is a practical simple test that requires a 30 m (100-ft) hallway. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. Absolute change from baseline at week 48.</description>
          <units>m</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.1" spread="48.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Posturography Score</title>
        <description>Computerized dynamic posturography (CDP) is a non-invasive specialized clinical assessment technique used to quantify the central nervous system adaptive mechanisms (sensory, motor and central) involved in the control of posture and balance, both in normal and abnormal conditions. Absolute change of speed in spontaneous speed condition from baseline at week 48.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Posturography Score</title>
          <description>Computerized dynamic posturography (CDP) is a non-invasive specialized clinical assessment technique used to quantify the central nervous system adaptive mechanisms (sensory, motor and central) involved in the control of posture and balance, both in normal and abnormal conditions. Absolute change of speed in spontaneous speed condition from baseline at week 48.</description>
          <units>m/s</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.111" spread="0.201"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.1055</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.111</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>0.201</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Excitability Testing: Supernormality (%)</title>
        <description>Nerve excitability testing is a non-invasive approach in investigating the pathophysiology of peripheral nerve disorders, which determines the electrical properties of the nerve membrane at the site of stimulation. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). During the 10-30 ms following the end of the refractory period, the axon increases its excitability and the nerve fiber is more easily excited (the supernormal period). Depolarization of the node of Ranvier excites the adjacent internodes, which then charge with electric current as capacitors. Supernormality depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Excitability Testing: Supernormality (%)</title>
          <description>Nerve excitability testing is a non-invasive approach in investigating the pathophysiology of peripheral nerve disorders, which determines the electrical properties of the nerve membrane at the site of stimulation. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). During the 10-30 ms following the end of the refractory period, the axon increases its excitability and the nerve fiber is more easily excited (the supernormal period). Depolarization of the node of Ranvier excites the adjacent internodes, which then charge with electric current as capacitors. Supernormality depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
          <units>percentage of supernormality</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.84" spread="28.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.2130</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>9.84</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>28.16</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Strength-duration Time Constant (ms)</title>
        <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
Strength-duration Time Constant (ms) is a measurement of excitability, defined as the duration of the stimulus that has twice the strength of the rheobase current (see below). The lower the rheobase is, the higher is the Strenght duration time constant. Accordingly, higer values of SDTC are associated with better outcome.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Strength-duration Time Constant (ms)</title>
          <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
Strength-duration Time Constant (ms) is a measurement of excitability, defined as the duration of the stimulus that has twice the strength of the rheobase current (see below). The lower the rheobase is, the higher is the Strenght duration time constant. Accordingly, higer values of SDTC are associated with better outcome.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.068" spread="0.112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0393</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.068</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>0.112</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rheobase (mA)</title>
        <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
Rheobase is the minimal strength of an electrical stimulus of infinitely long duration that is able to cause excitation. Low values are associated with better outcome (the nerve becomes more excitable).</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Rheobase (mA)</title>
          <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
Rheobase is the minimal strength of an electrical stimulus of infinitely long duration that is able to cause excitation. Low values are associated with better outcome (the nerve becomes more excitable).</description>
          <units>mA</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.905" spread="6.283"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0004</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-5.905</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>6.283</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Refractoriness (%)</title>
        <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline to week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Refractoriness (%)</title>
          <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline to week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
          <units>percentage of refractoriness</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.28" spread="32.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.3303</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-4.28</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>32.21</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Minimum Absolute Refractory Period (ms).</title>
        <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
        <time_frame>48 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Minimum Absolute Refractory Period (ms).</title>
          <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.000" spread="0.092"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.9229</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.000</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>0.092</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Absolute Refractory Period (ms).</title>
        <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
        <time_frame>Week 48</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MD1003</title>
            <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Absolute Refractory Period (ms).</title>
          <description>This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.&#xD;
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.277" spread="0.871"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>52 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>MD1003</title>
          <description>MD1003 100mg capsules, 1 capsule tid for 48 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Clear cell renal cell carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="14" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastric disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Burn oesophageal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Laboratory test interference</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>arthralgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>balance disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Muscle contractions involuntary</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep apnoea syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Rash papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Breast reconstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Dr Frédéric SEDEL, Chief Scientific Officer and Co-founder</name_or_title>
      <organization>MedDay Pharmaceuticals</organization>
      <phone>+33 1 80 40 14 40</phone>
      <email>frederic.sedel@medday-pharma.com</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/NCT02967679
org study id: MD1003CT2015-01 SERENDEM
nct id: NCT02967679
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The single-center, open-label Phase II study has the objective of assess the effect of MD1003
      on motor and sensory conduction in patients suffering from demyelinating polyneuropathies in
      15 subjects.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Motor Nerve Conduction Velocity (m/Sec)
time frame: 48 weeks
description: Absolute change from baseline at Week 48.
measure: Distal Latency (Msec)
time frame: 48 weeks
description: Absolute change from baseline at Week 48.
measure: F Wave Latency (Msec)
time frame: 48 weeks
description: Absolute change from baseline at Week 48.
measure: Length of Motor Nerve Potential
time frame: 48 weeks
description: Absolute change from baseline at W48.
measure: ONLS (Overall Neuropathy Limitations Scale)
time frame: 48 weeks
description: The ONLS focuses on upper and lower limb functions, and consists of a checklist for interviewing patients. It is scored from 0 to 5 on the upper limb section and from 0 to 7 on the lower limb section. A score of 0 indicates no limitations (the ceiling of the scale) and a score of 5 or 7 indicates no purposeful movement. Absolute change from baseline at week 48.
measure: Change From Baseline at Week 48 for Timed 10-meter Walk Test
time frame: 48 weeks
description: Absolute change from baseline at week 48. The patient is instructed to walk at normal pace for 10 meters. Start and stop of performance time coincides with the toes of the leading foot crossing the 2-m mark and the 8-m mark, respectively. From these data, the speed may be calculated by dividing the middle 6 m by the time (in seconds).
measure: Absolute Change From Baseline at Week 48 for Medical Research Council (MRC) Subscore (Total Muscle) and Total Score
time frame: 48 weeks
description: MRC score assessed in 19 muscles.
The muscle scale grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle.
The patient's effort is graded on a scale of 0-5:
Grade 5: Muscle contracts normally against full resistance. Grade 4: Muscle strength is reduced but muscle contraction can still move joint against resistance.
Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed. As an example, the elbow can be moved from full extension to full flexion starting with the arm hanging down at the side.
Grade 2: Muscle can move only if the resistance of gravity is removed. As an example, the elbow can be fully flexed only if the arm is maintained in a horizontal plane.
Grade 1: Only a trace or flicker of movement is seen or felt in the muscle or fasciculations are observed in the muscle.
Grade 0: No movement is observed.
measure: INCAT Sensory Sum Score (ISS)
time frame: 48 weeks
description: This sensory scale comprises pin prick and vibration sense plus a two point discrimination value in the arms and legs, and ranges from 0 ("normal sensation") to 20 ("most severe sensory deficit"). Absolute change from baseline at week 48.
measure: 6-minute Walk Test
time frame: 48 weeks
description: The 6MWT is a practical simple test that requires a 30 m (100-ft) hallway. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. Absolute change from baseline at week 48.
measure: Posturography Score
time frame: 48 weeks
description: Computerized dynamic posturography (CDP) is a non-invasive specialized clinical assessment technique used to quantify the central nervous system adaptive mechanisms (sensory, motor and central) involved in the control of posture and balance, both in normal and abnormal conditions. Absolute change of speed in spontaneous speed condition from baseline at week 48.
measure: Excitability Testing: Supernormality (%)
time frame: 48 weeks
description: Nerve excitability testing is a non-invasive approach in investigating the pathophysiology of peripheral nerve disorders, which determines the electrical properties of the nerve membrane at the site of stimulation. Absolute change from baseline at week 48.
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). During the 10-30 ms following the end of the refractory period, the axon increases its excitability and the nerve fiber is more easily excited (the supernormal period). Depolarization of the node of Ranvier excites the adjacent internodes, which then charge with electric current as capacitors. Supernormality depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
measure: Strength-duration Time Constant (ms)
time frame: 48 weeks
description: This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.
Strength-duration Time Constant (ms) is a measurement of excitability, defined as the duration of the stimulus that has twice the strength of the rheobase current (see below). The lower the rheobase is, the higher is the Strenght duration time constant. Accordingly, higer values of SDTC are associated with better outcome.
measure: Rheobase (mA)
time frame: 48 weeks
description: This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.
Rheobase is the minimal strength of an electrical stimulus of infinitely long duration that is able to cause excitation. Low values are associated with better outcome (the nerve becomes more excitable).
measure: Refractoriness (%)
time frame: 48 weeks
description: This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline to week 48.
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
measure: Minimum Absolute Refractory Period (ms).
time frame: 48 weeks
description: This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
measure: Maximum Absolute Refractory Period (ms).
time frame: Week 48
description: This secondary outcome measure is an electrophysiological testing endpoint. Absolute change from baseline at week 48.
After a nerve fiber is depolarized, a sequence of excitability changes, called the 'recovery cycle', occurs before the membrane potential returns to its resting stage. This cycle includes phases in which the nerve excitability is decreased ('refractory period' or increased ('supernormal period'). Refractoriness depends on many factors and its interpretation is therefore not univoqual. Data were provided for information only.
arm group label: MD1003
arm group type: Experimental
description: MD1003 100mg capsules, 1 capsule tid for 48 weeks
intervention type: Drug
intervention name: MD1003
arm group label: MD1003
other name: High Dose Biotin
criteria: 
gender: All
minimum age: 20 Years
maximum age: 85 Years
healthy volunteers: No
last name: Alain CREANGE, MD
role: Principal Investigator
affiliation: Hôpital Henri Mondor, Créteil, France
last name: Frederic Sedel, MD
role: Study Director
affiliation: Medday Pharmaceuticals
facility: 
country: France
url: http://www.medday-pharma.com
description: Sponsor
responsible party type: Sponsor
mesh term: Tooth Diseases
mesh term: Peripheral Nervous System Diseases
mesh term: Polyneuropathies
mesh term: Charcot-Marie-Tooth Disease
mesh term: Nerve Compression Syndromes
mesh term: Hereditary Sensory and Motor Neuropathy
mesh term: Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
mesh term: Biotin
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