<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/NCT01711853</url>
  </required_header>
  <id_info>
    <org_study_id>1160.166</org_study_id>
    <secondary_id>2011-003081-32</secondary_id>
    <nct_id>NCT01711853</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Pharmacokinetics and Pharmacodynamics of Dabigatran Etexilate in Patients With Stable Severe Renal Disease.</brief_title>
  <official_title>An Exploratory Study to Investigate the Pharmacokinetics and Effects of DABIgatran Etexilate in Patients With Stable Severe RENAL Disease: DabiRenal</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The study to be conducted is a prospective, open label trial. It is designed to evaluate the&#xD;
      pharmacokinetic/pharmacodynamic and coagulation parameters and safety of dabigatran etexilate&#xD;
      in patients with chronic kidney disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax,ss</measure>
    <time_frame>-0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h</time_frame>
    <description>Maximum concentration of Dabigatran etexilate in plasma at steady state was measured.&#xD;
The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCtau,ss</measure>
    <time_frame>-0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h</time_frame>
    <description>Area under the plasma concentration-time curve of the total dabigatran at steady state over a uniform dosing interval tau was measured.&#xD;
The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Renal Insufficiency, Chronic</condition>
  <arm_group>
    <arm_group_label>Dabigatran Etexilate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patient to receive a capsule containing 75 mg of dabigatran etexilate</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabigatran Etexilate</intervention_name>
    <description>Dabigatran Etexilate 75mg twice daily</description>
    <arm_group_label>Dabigatran Etexilate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Male and female patients aged 18 years and older&#xD;
&#xD;
          2. Impaired renal function defined as a stable Cockcroft-Gault and/or actual creatinine&#xD;
             clearance between 15-30 ml/min over the last 3 months before study participation.&#xD;
&#xD;
          3. The single use of either aspirin or Vitamin K Antagonists&#xD;
&#xD;
          4. Provision of informed consent.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Unstable renal function and Creatinin Clearance &lt;15mL/min&#xD;
&#xD;
          2. Patients treated with two or more platelet aggregation inhibitors&#xD;
&#xD;
          3. Use of or indication for therapeutic heparin&#xD;
&#xD;
          4. Patients with prosthetic heart valves&#xD;
&#xD;
          5. Haemorrhagic disorder or bleeding diathesis&#xD;
&#xD;
          6. Platelet count &lt;100 109/L) at screening or during the last 30 days before screening.&#xD;
&#xD;
          7. Participation in another drug trial in the last 30 days before screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>1160.166.31001 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>October 19, 2012</study_first_submitted>
  <study_first_submitted_qc>October 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <results_first_submitted>December 19, 2014</results_first_submitted>
  <results_first_submitted_qc>January 9, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 13, 2015</results_first_posted>
  <last_update_submitted>January 9, 2015</last_update_submitted>
  <last_update_submitted_qc>January 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 13, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dabigatran</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dabigatran 75 mg</title>
          <description>Oral administration of 1 capsule of Dabigatran etexilate 75 mg twice daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </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>Not treated</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated set (TS) which included all patients who had taken at least 1 dose of trial medication.</population>
      <group_list>
        <group group_id="B1">
          <title>Dabigatran 75 mg</title>
          <description>Oral administration of 1 capsule of Dabigatran etexilate 75 mg twice daily</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </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="72.7" spread="7.6"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cmax,ss</title>
        <description>Maximum concentration of Dabigatran etexilate in plasma at steady state was measured.&#xD;
The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.</description>
        <time_frame>-0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h</time_frame>
        <population>Pharmacokinetic set (PKS) which included all treated subjects that provided at least 1 observation for at least 1 primary pharmacokinetic endpoint without important protocol violations with respect to the evaluation of the pharmacokinetic endpoints and with predose values not greater than 5% of Cmax.</population>
        <group_list>
          <group group_id="O1">
            <title>Dabigatran 75 mg</title>
            <description>Oral administration of 1 capsule of Dabigatran etexilate 75 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax,ss</title>
          <description>Maximum concentration of Dabigatran etexilate in plasma at steady state was measured.&#xD;
The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.</description>
          <population>Pharmacokinetic set (PKS) which included all treated subjects that provided at least 1 observation for at least 1 primary pharmacokinetic endpoint without important protocol violations with respect to the evaluation of the pharmacokinetic endpoints and with predose values not greater than 5% of Cmax.</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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="207" spread="53.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Patients were classified into groups for renal function based on the median values for renal function (1: ≤ median GFR (Glomerular filtration rate), 2: &gt; median GFR).&#xD;
Median is calculated based on trial data of treated set</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.5186</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA model on the logarithmic scale; effects accounting for the following sources of variation: 'gender', 'age group', and 'renal function group'.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Patients were classified into groups for renal function based on the median values for renal function (1: ≤ median age, 2: &gt; median age).&#xD;
Median is calculated based on trial data of treated set</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.9883</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA model on the logarithmic scale; effects accounting for the following sources of variation: 'gender', 'age group', and 'renal function group'.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Patients were classified based on the gender distribution.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.7853</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA model on the logarithmic scale; effects accounting for the following sources of variation: 'gender', 'age group', and 'renal function group'.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUCtau,ss</title>
        <description>Area under the plasma concentration-time curve of the total dabigatran at steady state over a uniform dosing interval tau was measured.&#xD;
The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.</description>
        <time_frame>-0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>Dabigatran 75 mg</title>
            <description>Oral administration of 1 capsule of Dabigatran etexilate 75 mg twice daily</description>
          </group>
        </group_list>
        <measure>
          <title>AUCtau,ss</title>
          <description>Area under the plasma concentration-time curve of the total dabigatran at steady state over a uniform dosing interval tau was measured.&#xD;
The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.</description>
          <population>PKS</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="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2140" spread="51.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Patients were classified into groups for renal function based on the median values for renal function (1: ≤ median GFR, 2: &gt; median GFR).&#xD;
Median is calculated based on trial data of treated set</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4692</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA model on the logarithmic scale; effects accounting for the following sources of variation: 'gender', 'age group', and 'renal function group'.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Patients were classified into groups for renal function based on the median values for renal function (1: ≤ median age, 2: &gt; median age).&#xD;
Median is calculated based on trial data of treated set</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.9734</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA model on the logarithmic scale; effects accounting for the following sources of variation: 'gender', 'age group', and 'renal function group'.</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Patients were classified based on the gender distribution.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.9201</p_value>
            <method>ANOVA</method>
            <method_desc>ANOVA model on the logarithmic scale; effects accounting for the following sources of variation: 'gender', 'age group', and 'renal function group'.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to Day 11</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Dabigatran 75 mg</title>
          <description>Oral administration of 1 capsule of Dabigatran etexilate 75 mg twice daily</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="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MEDDRA 17.0</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="6" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Nail injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </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>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights</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/NCT01711853
org study id: 1160.166
secondary id: 2011-003081-32
nct id: NCT01711853
lead sponsor: 
The study to be conducted is a prospective, open label trial. It is designed to evaluate the
      pharmacokinetic/pharmacodynamic and coagulation parameters and safety of dabigatran etexilate
      in patients with chronic kidney disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cmax,ss
time frame: -0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h
description: Maximum concentration of Dabigatran etexilate in plasma at steady state was measured.
The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.
measure: AUCtau,ss
time frame: -0.5 hours (h), 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 23.5h, 47.5h, 71.5h, 95.5h, 119.5h, 155.5h, 167.5h, 168.5h, 169h, 170h, 171h, 172h, 174h, 176h, 179.5h, 180h, 192h, 216h, 240h
description: Area under the plasma concentration-time curve of the total dabigatran at steady state over a uniform dosing interval tau was measured.
The samples for pharmacokinetics had to be taken from 30 min before drug administration up to 11 days after drug administration.
arm group label: Dabigatran Etexilate
arm group type: Experimental
description: patient to receive a capsule containing 75 mg of dabigatran etexilate
intervention type: Drug
intervention name: Dabigatran Etexilate
description: Dabigatran Etexilate 75mg twice daily
arm group label: Dabigatran Etexilate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
country: Netherlands
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Renal Insufficiency
mesh term: Renal Insufficiency, Chronic
mesh term: Dabigatran
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 