<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/NCT01704404</url>
  </required_header>
  <id_info>
    <org_study_id>0091</org_study_id>
    <nct_id>NCT01704404</nct_id>
  </id_info>
  <brief_title>7 Days of TD-4208 in Subjects With Chronic Obstructive Pulmonary Disease</brief_title>
  <official_title>A Phase 2 Study of the Pharmacodynamics, Safety and Tolerability, and Pharmacokinetics of Multiple Doses of TD-4208 for 7 Days in Subjects Diagnosed With Chronic Obstructive Pulmonary Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mylan Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Theravance Biopharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Viatris Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will characterize the dose response of TD-4208 after 7 days of dosing in subjects&#xD;
      with Chronic Obstructive Pulmonary Disease (COPD).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Day 7 in Trough FEV1 (Forced Expiratory Volume in 1 Second)</measure>
    <time_frame>From baseline to day 7</time_frame>
  </primary_outcome>
  <other_outcome>
    <measure>Cmax</measure>
    <time_frame>From baseline to day 7</time_frame>
    <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
  </other_outcome>
  <other_outcome>
    <measure>Tmax</measure>
    <time_frame>From baseline to day 7</time_frame>
    <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Half-life</measure>
    <time_frame>From baseline to day 7</time_frame>
    <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
  </other_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>Dose 1 TD-4208</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>22 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 2 TD-4208</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>44 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 3 TD-4208</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>88 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 4 TD-4208</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>175 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 5 TD-4208</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>350 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 6 TD-4208</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>700 µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TD-4208</intervention_name>
    <arm_group_label>Dose 1 TD-4208</arm_group_label>
    <arm_group_label>Dose 2 TD-4208</arm_group_label>
    <arm_group_label>Dose 3 TD-4208</arm_group_label>
    <arm_group_label>Dose 4 TD-4208</arm_group_label>
    <arm_group_label>Dose 5 TD-4208</arm_group_label>
    <arm_group_label>Dose 6 TD-4208</arm_group_label>
    <other_name>revefenacin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is a male or female between the ages of 40 and 75 years (inclusive, at&#xD;
             randomization).&#xD;
&#xD;
          2. Subject:&#xD;
&#xD;
               -  Has an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) &lt;0.7&#xD;
                  at screening; and&#xD;
&#xD;
               -  Has a post-bronchodilator FEV1 at screening of between 30% and 80% (inclusive) of&#xD;
                  the predicted normal value.&#xD;
&#xD;
          3. Subject demonstrates at screening at least a 120 mL increase in FEV1 within 1 hour of&#xD;
             receiving 500 µg of ipratropium bromide from a PARI LC Sprint® nebulizer.&#xD;
&#xD;
          4. Females of non-childbearing potential. All male subjects must agree to use a highly&#xD;
             effective method of birth control with partners of childbearing potential during the&#xD;
             study and for 1 month after completion of study dosing.&#xD;
&#xD;
          5. Subject (or care giver) is able to properly prepare and administer study medication.&#xD;
&#xD;
          6. Subject is willing and able to give written informed consent to participate.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has had a COPD exacerbation or lung infection within 6 weeks before&#xD;
             randomization.&#xD;
&#xD;
          2. Subject has had an initiation of treatment, or a change in dose, of an inhaled or oral&#xD;
             corticosteroid, or long-acting beta2 agonist (LABA), or long-acting muscarinic&#xD;
             antagonist (LAMA) within 4 weeks before the qualifying ipratropium bromide response&#xD;
             test.&#xD;
&#xD;
          3. Subject is taking daily maintenance inhaled/systemic corticosteroids (&gt;1000 μg of&#xD;
             fluticasone propionate equivalent or ≥10 mg prednisone).&#xD;
&#xD;
          4. Subject has an uncontrolled hematologic, immunologic, renal, neurologic, hepatic,&#xD;
             endocrine, or other disease or condition based on information gathered from the&#xD;
             medical history, physical examination, or laboratory findings that might place the&#xD;
             subject at undue risk or potentially compromise the results or interpretation of the&#xD;
             study.&#xD;
&#xD;
          5. Subject has a history of significant cerebrovascular disease, coronary artery disease,&#xD;
             or cardiac arrhythmias. Subject has a history (or family history) of congenital&#xD;
             prolonged QTc (corrected QT interval) syndrome or has an abnormal clinically&#xD;
             significant electrocardiogram (ECG) at screening, including QTcB (QT interval&#xD;
             corrected for heart rate using Bazett's formula) value &gt;450 msec (males) or &gt;470 msec&#xD;
             (females); or shows evidence of clinically significant rhythm abnormality.&#xD;
&#xD;
          6. Subject has a known hypersensitivity to TD-4208 or similar drug class.&#xD;
&#xD;
          7. Subject has a history of alcoholism or drug abuse within 2 years prior to screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Monitor</last_name>
    <role>Study Director</role>
    <affiliation>Theravance Biopharma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>P3 Research Ltd</name>
      <address>
        <city>Wellington</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>New Zealand</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <results_first_submitted>January 17, 2017</results_first_submitted>
  <results_first_submitted_qc>January 20, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">March 13, 2017</results_first_posted>
  <last_update_submitted>February 22, 2022</last_update_submitted>
  <last_update_submitted_qc>February 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Long acting muscarinic antagonist</keyword>
  <keyword>Chronic Bronchitis</keyword>
  <keyword>Emphysema</keyword>
  <keyword>Chronic Obstructive Pulmonary Disease</keyword>
  <keyword>COPD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment 1</title>
          <description>Placebo, 44 µg, 88 µg, 350 µg, 700 µg</description>
        </group>
        <group group_id="P2">
          <title>Treatment 2</title>
          <description>Placebo, 22 µg, 88 µg, 350 µg, 700 µg</description>
        </group>
        <group group_id="P3">
          <title>Treatment 3</title>
          <description>Placebo, 22 µg, 88 µg, 175 µg, 700 µg</description>
        </group>
        <group group_id="P4">
          <title>Treatment 4</title>
          <description>22 µg, 44 µg, 175 µg, 700 µg</description>
        </group>
        <group group_id="P5">
          <title>Treatment 5</title>
          <description>22 µg, 44 µg, 175 µg, 350 µg</description>
        </group>
        <group group_id="P6">
          <title>Treatment 6</title>
          <description>Placebo, 44 µg, 88 µg, 175 µg, 350 µg</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="11"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="8"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Entire Study Population</title>
          <description>All subjects received Placebo and 4 of 6 TD-4208 dose levels:&#xD;
TD-4208 - 22 µg TD-4208 - 44 µg TD-4208 - 88 µg TD-4208 - 175 µg TD-4208 - 350 µg TD-4208 - 700 µg</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="62"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>year</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.2" spread="6.80"/>
                  </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="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline to Day 7 in Trough FEV1 (Forced Expiratory Volume in 1 Second)</title>
        <time_frame>From baseline to day 7</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose 1 TD-4208</title>
            <description>22 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O2">
            <title>Dose 2 TD-4208</title>
            <description>44 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O3">
            <title>Dose 3 TD-4208</title>
            <description>88 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O4">
            <title>Dose 4 TD-4208</title>
            <description>175 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O5">
            <title>Dose 5 TD-4208</title>
            <description>350 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O6">
            <title>Dose 6 TD-4208</title>
            <description>700 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O7">
            <title>Placebo</title>
            <description>Placebo&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Day 7 in Trough FEV1 (Forced Expiratory Volume in 1 Second)</title>
          <units>FEV1 (mL)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
                <count group_id="O2" value="39"/>
                <count group_id="O3" value="39"/>
                <count group_id="O4" value="39"/>
                <count group_id="O5" value="39"/>
                <count group_id="O6" value="40"/>
                <count group_id="O7" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.2" spread="19.21"/>
                    <measurement group_id="O2" value="92.8" spread="20.25"/>
                    <measurement group_id="O3" value="113.1" spread="19.55"/>
                    <measurement group_id="O4" value="151.9" spread="19.99"/>
                    <measurement group_id="O5" value="132.2" spread="19.02"/>
                    <measurement group_id="O6" value="119.4" spread="19.54"/>
                    <measurement group_id="O7" value="37.8" spread="16.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Cmax</title>
        <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
        <time_frame>From baseline to day 7</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose 1 TD-4208</title>
            <description>22 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O2">
            <title>Dose 2 TD-4208</title>
            <description>44 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O3">
            <title>Dose 3 TD-4208</title>
            <description>88 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O4">
            <title>Dose 4 TD-4208</title>
            <description>175 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O5">
            <title>Dose 5 TD-4208</title>
            <description>350 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O6">
            <title>Dose 6 TD-4208</title>
            <description>700 µg&#xD;
TD-4208</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax</title>
          <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
          <units>ng/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="37"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="35"/>
                <count group_id="O5" value="40"/>
                <count group_id="O6" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".0125" spread=".00627"/>
                    <measurement group_id="O2" value=".0224" spread=".00864"/>
                    <measurement group_id="O3" value=".0526" spread=".0214"/>
                    <measurement group_id="O4" value=".114" spread=".0488"/>
                    <measurement group_id="O5" value=".243" spread=".104"/>
                    <measurement group_id="O6" value=".577" spread=".261"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Tmax</title>
        <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
        <time_frame>From baseline to day 7</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose 1 TD-4208</title>
            <description>22 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O2">
            <title>Dose 2 TD-4208</title>
            <description>44 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O3">
            <title>Dose 3 TD-4208</title>
            <description>88 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O4">
            <title>Dose 4 TD-4208</title>
            <description>175 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O5">
            <title>Dose 5 TD-4208</title>
            <description>350 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O6">
            <title>Dose 6 TD-4208</title>
            <description>700 µg&#xD;
TD-4208</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax</title>
          <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="36"/>
                <count group_id="O3" value="35"/>
                <count group_id="O4" value="35"/>
                <count group_id="O5" value="40"/>
                <count group_id="O6" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".233" spread=".217"/>
                    <measurement group_id="O2" value=".233" spread="0.200"/>
                    <measurement group_id="O3" value="0.233" spread="0.200"/>
                    <measurement group_id="O4" value="0.233" spread="0.200"/>
                    <measurement group_id="O5" value="0.233" spread="0.217"/>
                    <measurement group_id="O6" value="0.233" spread="0.200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Half-life</title>
        <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
        <time_frame>From baseline to day 7</time_frame>
        <population>The number of subjects reported for plasma half lives are based on the actual evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose 1 TD-4208</title>
            <description>22 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O2">
            <title>Dose 2 TD-4208</title>
            <description>44 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O3">
            <title>Dose 3 TD-4208</title>
            <description>88 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O4">
            <title>Dose 4 TD-4208</title>
            <description>175 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O5">
            <title>Dose 5 TD-4208</title>
            <description>350 µg&#xD;
TD-4208</description>
          </group>
          <group group_id="O6">
            <title>Dose 6 TD-4208</title>
            <description>700 µg&#xD;
TD-4208</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Half-life</title>
          <description>Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.&#xD;
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.</description>
          <population>The number of subjects reported for plasma half lives are based on the actual evaluable PK data.</population>
          <units>hours</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="31"/>
                <count group_id="O6" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O5" value="25.1" spread="7.89"/>
                    <measurement group_id="O6" value="23.0" spread="7.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>13 weeks</time_frame>
      <desc>The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dose 1 TD-4208</title>
          <description>22 µg&#xD;
TD-4208</description>
        </group>
        <group group_id="E2">
          <title>Dose 2 TD-4208</title>
          <description>44 µg&#xD;
TD-4208</description>
        </group>
        <group group_id="E3">
          <title>Dose 3 TD-4208</title>
          <description>88 µg&#xD;
TD-4208</description>
        </group>
        <group group_id="E4">
          <title>Dose 4 TD-4208</title>
          <description>175 µg&#xD;
TD-4208</description>
        </group>
        <group group_id="E5">
          <title>Dose 5 TD-4208</title>
          <description>350 µg&#xD;
TD-4208</description>
        </group>
        <group group_id="E6">
          <title>Dose 6 TD-4208</title>
          <description>700 µg&#xD;
TD-4208</description>
        </group>
        <group group_id="E7">
          <title>Placebo</title>
          <description>Placebo&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 15.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="42"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Transient Ischaemic Attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="42"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="42"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>4</frequency_threshold>
        <default_vocab>MedDRA 15.0</default_vocab>
        <default_assessment>Non-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="41"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="39"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="40"/>
                <counts group_id="E4" subjects_affected="13" subjects_at_risk="37"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="41"/>
                <counts group_id="E6" subjects_affected="9" subjects_at_risk="37"/>
                <counts group_id="E7" subjects_affected="16" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="37"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="41"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="37"/>
                <counts group_id="E7" events="9" subjects_affected="9" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="61"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="41"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E7" events="4" subjects_affected="4" subjects_at_risk="61"/>
              </event>
              <event>
                <sub_title>COPD</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="61"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="41"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="61"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="41"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="61"/>
              </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 PI may communicate the trial results generated by the PI, but only after the first publication or presentation of the combined study results generated by all participating sites. The Sponsor can then review trial results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The Sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Clinical Development &amp; Medical Affairs</name_or_title>
      <organization>Theravance Biopharma</organization>
      <phone>1-855-633-8479</phone>
      <email>medinfo@theravance.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/NCT01704404
org study id: 0091
nct id: NCT01704404
lead sponsor: 
collaborator: 
has dmc: No
This study will characterize the dose response of TD-4208 after 7 days of dosing in subjects
      with Chronic Obstructive Pulmonary Disease (COPD).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline to Day 7 in Trough FEV1 (Forced Expiratory Volume in 1 Second)
time frame: From baseline to day 7
measure: Cmax
time frame: From baseline to day 7
description: Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.
measure: Tmax
time frame: From baseline to day 7
description: Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.
measure: Plasma Half-life
time frame: From baseline to day 7
description: Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.
Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.
arm group label: Dose 1 TD-4208
arm group type: Experimental
description: 22 µg
arm group label: Dose 2 TD-4208
arm group type: Experimental
description: 44 µg
arm group label: Dose 3 TD-4208
arm group type: Experimental
description: 88 µg
arm group label: Dose 4 TD-4208
arm group type: Experimental
description: 175 µg
arm group label: Dose 5 TD-4208
arm group type: Experimental
description: 350 µg
arm group label: Dose 6 TD-4208
arm group type: Experimental
description: 700 µg
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: TD-4208
arm group label: Dose 1 TD-4208
arm group label: Dose 2 TD-4208
arm group label: Dose 3 TD-4208
arm group label: Dose 4 TD-4208
arm group label: Dose 5 TD-4208
arm group label: Dose 6 TD-4208
other name: revefenacin
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Medical Monitor
role: Study Director
affiliation: Theravance Biopharma
facility: 
country: New Zealand
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 