<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/NCT02263547</url>
  </required_header>
  <id_info>
    <org_study_id>GZ-2013-11023</org_study_id>
    <nct_id>NCT02263547</nct_id>
  </id_info>
  <brief_title>Rapid Elimination Procedure of Teriflunomide With Colestipol Hydrochloride</brief_title>
  <acronym>TERCOL</acronym>
  <official_title>Rapid Elimination Procedure of Teriflunomide With Colestipol Hydrochloride</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Derrick Scott Robertson</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genzyme, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of South Florida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of South Florida</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective To determine if colestipol hydrochloride tablets can accelerate the&#xD;
      elimination of teriflunomide. Teriflunomide will be administered for 14 days followed by&#xD;
      colestipol dosing of 11 days. Total duration of the study is 40 days.&#xD;
&#xD;
      Secondary Objectives To collect information on the pattern of side effects with use of&#xD;
      colestipol hydrochloride after teriflunomide administration and to determine the best&#xD;
      duration of therapy needed for adequate elimination&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      participants will be followed for 40 days to allow for time to administer a loading dose of&#xD;
      teriflunomide and observe the elimination of that drug using colestipol hcl.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    PK time points were not being met as expected. Determination that risks outweighed benefit.&#xD;
  </why_stopped>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 1</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Outcome Measures: Teriflunomide Concentrations at Day 28</measure>
    <time_frame>28 days after the start in the study</time_frame>
    <description>After receiving 14 days of teriflunomide, participants will take 11 days of colestipol to wash out the teriflunomide (measuring the levels of teriflunomide in the blood at each visit)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets.</measure>
    <time_frame>duration of study about 50 days</time_frame>
    <description>The last blood draw will be about 50 days from the start of the study</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Teriflunomide Elimination</condition>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>teriflunomide elimination with colestipol</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>teriflunomide</intervention_name>
    <arm_group_label>teriflunomide elimination with colestipol</arm_group_label>
    <other_name>Aubagio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colestipol</intervention_name>
    <arm_group_label>teriflunomide elimination with colestipol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        To be eligible for entry into this study, candidates must meet all of the following&#xD;
        eligibility criteria at the time of the baseline visit:&#xD;
&#xD;
          1. Participants having provided informed consent with signature on informed consent form:&#xD;
             the informed consent process should be complete with full discussion of all&#xD;
             requirements and possible risks.&#xD;
&#xD;
          2. Healthy volunteer*&#xD;
&#xD;
          3. Aged 18-45 years, inclusive&#xD;
&#xD;
          4. Body Mass Index of 18-29 kg/m2 (body weight of 40-85 kg for women and 50-95 kg for&#xD;
             men) *Healthy volunteer is defined as free of concomitant medications and use of&#xD;
             either treatment, as deemed by the Investigator, is not contraindicated with any past&#xD;
             medical history of the participant.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current smoker or past history as smoker.&#xD;
&#xD;
          2. Unable to provide informed consent to participate in the study Such as a mental&#xD;
             condition rendering the participant unable to understand the nature, scope, and&#xD;
             possible consequences of the study&#xD;
&#xD;
          3. Participant unlikely to comply with protocol as determined by Investigator, eg,&#xD;
             uncooperative attitude, inability to return for follow-up visits&#xD;
&#xD;
          4. Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major&#xD;
             systemic disease making implementation of the protocol or interpretation of the study&#xD;
             results difficult or that would put the participant at risk by participating in the&#xD;
             study&#xD;
&#xD;
          5. Persistent significant or severe infection, either acute or chronic&#xD;
&#xD;
          6. Recent history of drug or alcohol abuse within that past 6 months (participants will&#xD;
             be asked to refrain from alcohol and drug use during the course of the study)&#xD;
&#xD;
          7. Participant is the Investigator or any Sub-investigator, research assistant,&#xD;
             pharmacist, study coordinator, other staff or relative thereof, directly involved in&#xD;
             the conduct of the protocol&#xD;
&#xD;
          8. Prior use of any investigational drug in the preceding 6 months&#xD;
&#xD;
          9. Liver function impairment or persisting elevations (confirmed by retest) of alanine&#xD;
             aminotransferase (ALT), aspartate aminotransferase (AST), or direct bilirubin greater&#xD;
             than 2x the upper limit of normal range (ULN).&#xD;
&#xD;
         10. Pregnant or breast-feeding women or those who plan to become pregnant during the study&#xD;
&#xD;
         11. Women of childbearing potential not protected by effective contraceptive method of&#xD;
             birth control and/or who are unwilling or unable to be tested for pregnancy.&#xD;
&#xD;
         12. Participants wishing to parent children (be a partner in the conception of a child)&#xD;
             during the course of the trial.&#xD;
&#xD;
         13. Participants with significantly impaired bone marrow function or significant anemia,&#xD;
             leukopenia, or thrombocytopenia (confirmed by retest):&#xD;
&#xD;
               -  Hematocrit &lt; 35% and/or&#xD;
&#xD;
               -  Absolute white blood cell count &lt; 3000 cells/mm3 (μL) and/or&#xD;
&#xD;
               -  Platelet count &lt; 150 000 cells/mm3 (μL) and/or- Absolute neutrophil ≤ 1500&#xD;
                  cells/mm3 (μL)&#xD;
&#xD;
         14. Any known history of severe preexisting constipation&#xD;
&#xD;
         15. History of swallowing disorder or difficulty swallowing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>USF Carol and Frank Morsani Center for Advanced Healthcare</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>September 30, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <results_first_submitted>October 30, 2017</results_first_submitted>
  <results_first_submitted_qc>April 12, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 1, 2019</results_first_posted>
  <last_update_submitted>April 1, 2020</last_update_submitted>
  <last_update_submitted_qc>April 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of South Florida</investigator_affiliation>
    <investigator_full_name>Derrick Scott Robertson</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>teriflunomide</keyword>
  <keyword>colestipol hcl</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Teriflunomide</mesh_term>
    <mesh_term>Colestipol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Enrollment occurred from March 2015 through May 2016 at the USF Carol and Frank Morsani Center.</recruitment_details>
      <pre_assignment_details>Participants were healthy individuals with no significant health history or concomitant medication use.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Teriflunomide Elimination With Colestipol</title>
          <description>teriflunomide&#xD;
Colestipol</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </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>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Teriflunomide Elimination With Colestipol</title>
          <description>teriflunomide&#xD;
Colestipol</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.5" spread="7.9"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.9" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Primary Outcome Measures: Teriflunomide Concentrations at Day 28</title>
        <description>After receiving 14 days of teriflunomide, participants will take 11 days of colestipol to wash out the teriflunomide (measuring the levels of teriflunomide in the blood at each visit)</description>
        <time_frame>28 days after the start in the study</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Teriflunomide Elimination With Colestipol</title>
            <description>teriflunomide&#xD;
Colestipol</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Outcome Measures: Teriflunomide Concentrations at Day 28</title>
          <description>After receiving 14 days of teriflunomide, participants will take 11 days of colestipol to wash out the teriflunomide (measuring the levels of teriflunomide in the blood at each visit)</description>
          <units>teriflunomide level (mcg/ml)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.36" spread="4.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets.</title>
        <description>The last blood draw will be about 50 days from the start of the study</description>
        <time_frame>duration of study about 50 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Teriflunomide Elimination With Colestipol</title>
            <description>teriflunomide&#xD;
Colestipol</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets.</title>
          <description>The last blood draw will be about 50 days from the start of the study</description>
          <units>percentage change in teriflunomide level</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>8 days after colestipol hcl administered</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-56.4" spread="21.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>14 days after colestipol hcl administered</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-74.9" spread="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>26 days after colestipol hcl administered</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-94.9" spread="6.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>36 days after colestipol hcl administered</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-96.9" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Teriflunomide Elimination With Colestipol</title>
          <description>teriflunomide&#xD;
Colestipol</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
              </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="12" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anticipated Adverse events</sub_title>
                <description>nausea, diarrhea, abdominal discomfort, heartburn</description>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="14"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>small number of subjects analyzed with some lost to followup</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Assistant Director of Research</name_or_title>
      <organization>University of South Florida, COM Neurology</organization>
      <phone>8139746378</phone>
      <email>aaungst@health.usf.edu</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/NCT02263547
org study id: GZ-2013-11023
nct id: NCT02263547
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Primary Objective To determine if colestipol hydrochloride tablets can accelerate the
      elimination of teriflunomide. Teriflunomide will be administered for 14 days followed by
      colestipol dosing of 11 days. Total duration of the study is 40 days.

      Secondary Objectives To collect information on the pattern of side effects with use of
      colestipol hydrochloride after teriflunomide administration and to determine the best
      duration of therapy needed for adequate elimination
participants will be followed for 40 days to allow for time to administer a loading dose of
      teriflunomide and observe the elimination of that drug using colestipol hcl.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Primary Outcome Measures: Teriflunomide Concentrations at Day 28
time frame: 28 days after the start in the study
description: After receiving 14 days of teriflunomide, participants will take 11 days of colestipol to wash out the teriflunomide (measuring the levels of teriflunomide in the blood at each visit)
measure: Secondary Outcome Measure: Mean Percentage Change of Serum Teriflunomide Levels Percentage Change of Teriflunomide Concentrations at Day 8, Day 14, Day 26 ad Day 36 Following Administration of Colestipol Hydrochloride Tablets.
time frame: duration of study about 50 days
description: The last blood draw will be about 50 days from the start of the study
arm group label: teriflunomide elimination with colestipol
arm group type: Other
intervention type: Drug
intervention name: teriflunomide
arm group label: teriflunomide elimination with colestipol
other name: Aubagio
intervention type: Drug
intervention name: Colestipol
arm group label: teriflunomide elimination with colestipol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of South Florida
investigator full name: Derrick Scott Robertson
investigator title: Assistant Professor
mesh term: Teriflunomide
mesh term: Colestipol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: small number of subjects analyzed with some lost to followup
point of contact: 