<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/NCT01734772</url>
  </required_header>
  <id_info>
    <org_study_id>1160.142</org_study_id>
    <secondary_id>2012-002656-16</secondary_id>
    <nct_id>NCT01734772</nct_id>
  </id_info>
  <brief_title>Investigation of Drug-drug Interaction of Dabigatran and Ticagrelor</brief_title>
  <official_title>Investigation of Drug-drug Interaction of Dabigatran and Ticagrelor Under Steady State Conditions in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To investigate the pharmacokinetic and pharmacodynamic interaction of dabigatran and&#xD;
      ticagrelor under steady state conditions; to investigate the effect of staggered&#xD;
      administration of ticagrelor loading dose on dabigatran exposure (in Part II)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2013</completion_date>
  <primary_completion_date type="Actual">June 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)</measure>
    <time_frame>47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours</time_frame>
    <description>Area under the concentration-time curve of dabigatran etexilate in plasma at steady state over the uniform dosing interval τ (AUCτ,ss).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss)</measure>
    <time_frame>47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours</time_frame>
    <description>Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss).</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Reference (Part 1/A, Part 2/C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>multiple doses of dabigatran (alone)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Test 1 (Part 1/Treatment B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>concomitant administration of dabigatran and ticagrelor</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Test 2 (Part 2/Treatment D)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>staggered administration of ticagrelor and dabigatran</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dabigatran etexilate</intervention_name>
    <description>multiple doses of dabigatran</description>
    <arm_group_label>Test 1 (Part 1/Treatment B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dabigatran etexilate</intervention_name>
    <description>medium dose dabigatran</description>
    <arm_group_label>Reference (Part 1/A, Part 2/C)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ticagrelor</intervention_name>
    <description>loading dose of ticagrelor</description>
    <arm_group_label>Test 1 (Part 1/Treatment B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ticagrelor</intervention_name>
    <description>multiple doses of ticagrelor</description>
    <arm_group_label>Test 1 (Part 1/Treatment B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ticagrelor</intervention_name>
    <description>loading dose of ticagrelor</description>
    <arm_group_label>Test 2 (Part 2/Treatment D)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dabigatran etexilate</intervention_name>
    <description>single dose of dabigatran</description>
    <arm_group_label>Test 2 (Part 2/Treatment D)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        1. Healthy male subjects.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
        1. Any relevant deviation from healthy conditions.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>1160.142.1 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Biberach</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1160/1160.142_U13-2049-01.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>April 2014</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <results_first_submitted>April 2, 2014</results_first_submitted>
  <results_first_submitted_qc>April 2, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 5, 2014</results_first_posted>
  <last_update_submitted>April 2, 2014</last_update_submitted>
  <last_update_submitted_qc>April 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 5, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dabigatran</mesh_term>
    <mesh_term>Ticagrelor</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Part 1</title>
          <description>In part 1, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, ticagrelor treatment was added starting with the concomitant administration of a 180 mg ticagrelor loading dose followed by 90 mg ticagrelor twice daily. Dabigatran PK profiles were taken on day 1 of the test treatment and day 4 of the test treatment.</description>
        </group>
        <group group_id="P2">
          <title>Part 2</title>
          <description>In part 2, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, 180 mg ticagrelor were given 2 hours after the morning dose of 110 mg dabigatran etexilate and dabigatran PK profile were taken on this day 1 of the test treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" 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 group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated Set which includes all subjects who were documented to have received at least 1 dose of trial medication.</population>
      <group_list>
        <group group_id="B1">
          <title>Part 1</title>
          <description>In part 1, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, ticagrelor treatment was added starting with the concomitant administration of a 180 mg ticagrelor loading dose followed by 90 mg ticagrelor twice daily. Dabigatran PK profiles were taken on day 1 of the test treatment and day 4 of the test treatment.</description>
        </group>
        <group group_id="B2">
          <title>Part 2</title>
          <description>In part 2, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, 180 mg ticagrelor were given 2 hours after the morning dose of 110 mg dabigatran etexilate and dabigatran PK profile were taken on this day 1 of the test treatment.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="24"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="48"/>
          </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="28.0" spread="7.2"/>
                    <measurement group_id="B2" value="28.6" spread="7.1"/>
                    <measurement group_id="B3" value="28.3" spread="7.15"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)</title>
        <description>Area under the concentration-time curve of dabigatran etexilate in plasma at steady state over the uniform dosing interval τ (AUCτ,ss).</description>
        <time_frame>47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours</time_frame>
        <population>Pharmacokinetic set: This subject set included all subjects in the TS who provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability and who had not vomiting at or before 2 times the median tmax,ss of the trial medications on PK study days of both trial parts.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabigratan Etexilate 110mg Bid Alone - Part 1</title>
            <description>Dabigatran Etexilate 110mg twice daily (bid) for 3 days</description>
          </group>
          <group group_id="O2">
            <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 1</title>
            <description>Single loading dose of Ticagrelor 180 mg on day 1 together with Dabigatran Etexilate 110mg bid.</description>
          </group>
          <group group_id="O3">
            <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 90mg Bid - Part 1</title>
            <description>Multiple dosing of 90 mg bid on days 2 and 3 and 90mg on day 4 together with Dabigatran Etexilate 110mg bid on days 2 and 3 and 110mg in the morning on day 4.</description>
          </group>
          <group group_id="O4">
            <title>Dabigratan Etexilate 110mg Bid Alone - Part 2</title>
            <description>Dabigatran Etexilate 110mg twice daily (bid) for 3 days</description>
          </group>
          <group group_id="O5">
            <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 2</title>
            <description>Dabigatran Etexilate 110mg morning dose followed by 180mg Ticagrelor 2 hours later.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)</title>
          <description>Area under the concentration-time curve of dabigatran etexilate in plasma at steady state over the uniform dosing interval τ (AUCτ,ss).</description>
          <population>Pharmacokinetic set: This subject set included all subjects in the TS who provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability and who had not vomiting at or before 2 times the median tmax,ss of the trial medications on PK study days of both trial parts.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="23"/>
                <count group_id="O3" value="23"/>
                <count group_id="O4" value="23"/>
                <count group_id="O5" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="551" spread="59.0"/>
                    <measurement group_id="O2" value="817" spread="43.3"/>
                    <measurement group_id="O3" value="689" spread="55.1"/>
                    <measurement group_id="O4" value="660" spread="39.6"/>
                    <measurement group_id="O5" value="844" spread="43.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Relative bioavailability</non_inferiority_desc>
            <p_value>0.9456</p_value>
            <p_value_desc>p-value for ratio outside interval 80% - 125%</p_value_desc>
            <method>ANOVA</method>
            <method_desc>Adjustment for effects 'subject' and 'treatment'.</method_desc>
            <param_type>geometric Mean Ratio</param_type>
            <param_value>149.38</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>37.6</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_lower_limit>124.388</ci_lower_limit>
            <ci_upper_limit>179.383</ci_upper_limit>
            <estimate_desc>The dispersion value is actually the intraindividual gCV.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Relative bioavailability</non_inferiority_desc>
            <p_value>0.5481</p_value>
            <p_value_desc>p-value for ratio outside interval 80% - 125%</p_value_desc>
            <method>ANOVA</method>
            <method_desc>Adjustment for effects 'subject' and 'treatment'.</method_desc>
            <param_type>geometric Mean Ratio</param_type>
            <param_value>126.47</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>33.3</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_lower_limit>107.363</ci_lower_limit>
            <ci_upper_limit>148.967</ci_upper_limit>
            <estimate_desc>The dispersion value is actually the intraindividual gCV.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Relative bioavailability</non_inferiority_desc>
            <p_value>0.5665</p_value>
            <p_value_desc>p-value for ratio outside interval 80% - 125%</p_value_desc>
            <method>ANOVA</method>
            <method_desc>Adjustment for effects 'subject' and 'treatment'.</method_desc>
            <param_type>geometric Mean Ratio</param_type>
            <param_value>127.01</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>31.6</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_lower_limit>108.047</ci_lower_limit>
            <ci_upper_limit>149.295</ci_upper_limit>
            <estimate_desc>The dispersion value is actually the intraindividual gCV.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss)</title>
        <description>Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss).</description>
        <time_frame>47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours</time_frame>
        <population>Pharmacokinetic set: This subject set included all subjects in the TS who provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability and who had not vomiting at or before 2 times the median tmax,ss of the trial medications on PK study days of both trial parts.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabigratan Etexilate 110mg Bid Alone - Part 1</title>
            <description>Dabigatran Etexilate 110mg twice daily (bid) for 3 days</description>
          </group>
          <group group_id="O2">
            <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 1</title>
            <description>Single loading dose of Ticagrelor 180 mg on day 1 together with Dabigatran Etexilate 110mg bid.</description>
          </group>
          <group group_id="O3">
            <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 90mg Bid - Part 1</title>
            <description>Multiple dosing of 90 mg bid on days 2 and 3 and 90mg on day 4 together with Dabigatran Etexilate 110mg bid on days 2 and 3 and 110mg in the morning on day 4.</description>
          </group>
          <group group_id="O4">
            <title>Dabigratan Etexilate 110mg Bid Alone - Part 2</title>
            <description>Dabigatran Etexilate 110mg twice daily (bid) for 3 days</description>
          </group>
          <group group_id="O5">
            <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 2</title>
            <description>Dabigatran Etexilate 110mg morning dose followed by 180mg Ticagrelor 2 hours later.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss)</title>
          <description>Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss).</description>
          <population>Pharmacokinetic set: This subject set included all subjects in the TS who provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability and who had not vomiting at or before 2 times the median tmax,ss of the trial medications on PK study days of both trial parts.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="23"/>
                <count group_id="O3" value="23"/>
                <count group_id="O4" value="23"/>
                <count group_id="O5" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.6" spread="69.3"/>
                    <measurement group_id="O2" value="136" spread="45.4"/>
                    <measurement group_id="O3" value="106" spread="65.1"/>
                    <measurement group_id="O4" value="97.6" spread="46.5"/>
                    <measurement group_id="O5" value="121" spread="45.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Relative bioavailability</non_inferiority_desc>
            <p_value>0.9841</p_value>
            <p_value_desc>p-value for ratio outside interval 80% - 125%</p_value_desc>
            <method>ANOVA</method>
            <method_desc>Adjustment for effects 'subject' and 'treatment'.</method_desc>
            <param_type>geometric Mean Ratio</param_type>
            <param_value>164.74</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>42.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_lower_limit>133.945</ci_lower_limit>
            <ci_upper_limit>202.619</ci_upper_limit>
            <estimate_desc>The dispersion value is actually the intraindividual gCV.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Relative bioavailability</non_inferiority_desc>
            <p_value>0.6003</p_value>
            <p_value_desc>p-value for ratio outside interval 80% - 125%</p_value_desc>
            <method>ANOVA</method>
            <method_desc>Adjustment for effects 'subject' and 'treatment'.</method_desc>
            <param_type>geometric Mean Ratio</param_type>
            <param_value>128.61</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>39.0</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_lower_limit>106.370</ci_lower_limit>
            <ci_upper_limit>155.495</ci_upper_limit>
            <estimate_desc>The dispersion value is actually the intraindividual gCV.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O5</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Relative bioavailability</non_inferiority_desc>
            <p_value>0.4656</p_value>
            <p_value_desc>p-value for ratio outside interval 80% - 125%</p_value_desc>
            <method>ANOVA</method>
            <method_desc>Adjustment for effects 'subject' and 'treatment'.</method_desc>
            <param_type>gMean Ratio</param_type>
            <param_value>123.82</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>36.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_lower_limit>102.695</ci_lower_limit>
            <ci_upper_limit>149.288</ci_upper_limit>
            <estimate_desc>The dispersion value is actually the intraindividual gCV.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>11 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Dabigratan Etexilate 110mg Bid Alone - Part 1</title>
          <description>Dabigatran Etexilate 110mg twice daily (bid) for 3 days</description>
        </group>
        <group group_id="E2">
          <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 1</title>
          <description>Single loading dose of Ticagrelor 180 mg on day 1 together with Dabigatran Etexilate 110mg bid.</description>
        </group>
        <group group_id="E3">
          <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 90mg Bid - Part 1</title>
          <description>Multiple dosing of 90 mg bid on days 2 and 3 and 90mg on day 4 together with Dabigatran Etexilate 110mg bid on days 2 and 3 and 110mg once on day 4.</description>
        </group>
        <group group_id="E4">
          <title>Dabigratan Etexilate 110mg Bid Alone - Part 2</title>
          <description>Dabigatran Etexilate 110mg twice daily (bid) for 3 days</description>
        </group>
        <group group_id="E5">
          <title>Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 2</title>
          <description>Dabigatran Etexilate 110mg morning dose followed by 180mg Ticagrelor 2 hours later.</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="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MEDDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim Call Center</name_or_title>
      <organization>Boehringer Ingelheim Pharmaceuticals</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.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/NCT01734772
org study id: 1160.142
secondary id: 2012-002656-16
nct id: NCT01734772
lead sponsor: 
To investigate the pharmacokinetic and pharmacodynamic interaction of dabigatran and
      ticagrelor under steady state conditions; to investigate the effect of staggered
      administration of ticagrelor loading dose on dabigatran exposure (in Part II)
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)
time frame: 47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours
description: Area under the concentration-time curve of dabigatran etexilate in plasma at steady state over the uniform dosing interval τ (AUCτ,ss).
measure: Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss)
time frame: 47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours
description: Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss).
arm group label: Reference (Part 1/A, Part 2/C)
arm group type: Experimental
description: multiple doses of dabigatran (alone)
arm group label: Test 1 (Part 1/Treatment B)
arm group type: Experimental
description: concomitant administration of dabigatran and ticagrelor
arm group label: Test 2 (Part 2/Treatment D)
arm group type: Experimental
description: staggered administration of ticagrelor and dabigatran
intervention type: Drug
intervention name: dabigatran etexilate
description: multiple doses of dabigatran
arm group label: Test 1 (Part 1/Treatment B)
intervention type: Drug
intervention name: dabigatran etexilate
description: medium dose dabigatran
arm group label: Reference (Part 1/A, Part 2/C)
intervention type: Drug
intervention name: ticagrelor
description: loading dose of ticagrelor
arm group label: Test 1 (Part 1/Treatment B)
intervention type: Drug
intervention name: ticagrelor
description: multiple doses of ticagrelor
arm group label: Test 1 (Part 1/Treatment B)
intervention type: Drug
intervention name: ticagrelor
description: loading dose of ticagrelor
arm group label: Test 2 (Part 2/Treatment D)
intervention type: Drug
intervention name: dabigatran etexilate
description: single dose of dabigatran
arm group label: Test 2 (Part 2/Treatment D)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
country: Germany
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1160/1160.142_U13-2049-01.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Dabigatran
mesh term: Ticagrelor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 