<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/NCT02183389</url>
  </required_header>
  <id_info>
    <org_study_id>1218.28</org_study_id>
    <nct_id>NCT02183389</nct_id>
  </id_info>
  <brief_title>Bioavailability of Warfarin After Coadministration With Multiple Doses of BI 1356 Compared to the Bioavailability of Warfarin Alone in Healthy Male Volunteers</brief_title>
  <official_title>Relative Bioavailability of a Single Oral Dose of Warfarin (10 mg qd) After Coadministration With Multiple Oral Doses of BI 1356 (5 mg qd) Compared to the Bioavailability of a Single Oral Dose of Warfarin (10 mg qd) Alone in Healthy Male Volunteers (an Open Label, Two Periods, Fixed-sequence, Clinical Phase I Study)</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 whether and to what extent BI 1356 affects pharmacokinetic and pharmacodynamic&#xD;
      parameters of warfarin&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2008</start_date>
  <primary_completion_date type="Actual">October 2008</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum measured concentration of the analyte in plasma (Cmax)</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration time curve (AUC) of the analyte in plasma at different time points</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to the maximum concentration of the analyte in plasma (tmax)</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant in plasma (λz)</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half life of the analyte in plasma (t1/2)</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of the analyte in the body after p.o. administration (MRTpo)</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance of the analyte in the plasma after extravascular administration (CL/F)</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)</measure>
    <time_frame>Up to 168 hours after start of study medication</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up 42 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant changes in physical examination</measure>
    <time_frame>Up to 14 days after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant changes in vital signs (Blood Pressure (BP), Pulse Rate (PR))</measure>
    <time_frame>Up to 14 days after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant changes in 12-lead resting electrocardiogram (ECG)</measure>
    <time_frame>Up to 14 days after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with relevant changes in laboratory values</measure>
    <time_frame>Up to 14 days after last study drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability a 4-point scale by the investigator</measure>
    <time_frame>Up 42 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International normalised ratio, area under the concentration time curve of the analyte in plasma over the time interval from time zero to 168 hours (INR AUC0-168)</measure>
    <time_frame>Up to 168 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International normalised ratio, maximum concentration of the analyte in plasma (INRmax)</measure>
    <time_frame>Up to 168 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prothrombin time, area under the concentration time curve of the analyte in plasma over the time interval from time zero to 168 hours (PT AUC0-168)</measure>
    <time_frame>Up to 168 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prothrombin time, maximum concentration of the analyte in plasma (PTmax)</measure>
    <time_frame>Up to 168 hours after start of treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment B: BI 1356 and Warfarin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BI 1356 for 12 days combined with a single dose of warfarin on day 6</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment A: Warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Warfarin as single dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin</intervention_name>
    <arm_group_label>Treatment A: Warfarin</arm_group_label>
    <arm_group_label>Treatment B: BI 1356 and Warfarin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1356</intervention_name>
    <arm_group_label>Treatment B: BI 1356 and Warfarin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males according to the following criteria:&#xD;
&#xD;
               -  Based upon a complete medical history, including the physical examination, vital&#xD;
                  signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG),&#xD;
                  clinical laboratory tests&#xD;
&#xD;
          -  Age ≥ 18 and Age ≤ 50 years&#xD;
&#xD;
          -  BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index)&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with good clinical practice (GCP) and the local legislation&#xD;
&#xD;
          -  Homozygote wild-type carriers (*1/*1) of cytochrome P 450 (CYP) 2C9&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including BP, PR and ECG) deviating from&#xD;
             normal and of clinical relevance&#xD;
&#xD;
          -  Any evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Surgery of the gastrointestinal tract (except appendectomy)&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  History of relevant orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of relevant allergy/hypersensitivity (including allergy to drug or its&#xD;
             excipients)&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24 hours) within at least one month or less&#xD;
             than 10 half-lives of the respective drug prior to administration or during the trial&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial or that prolong&#xD;
             the QT/QTc interval based on the knowledge at the time of protocol preparation within&#xD;
             10 days prior to administration or during the trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within two months prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Smoker (&gt; 10 cigarettes or &gt; 3 cigars or &gt; 3 pipes/day)&#xD;
&#xD;
          -  Inability to refrain from smoking on trial days&#xD;
&#xD;
          -  Alcohol abuse (more than 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL within four weeks prior to administration or during&#xD;
             the trial)&#xD;
&#xD;
          -  Excessive physical activities (within one week prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range that is of clinical relevance&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a&#xD;
             QTc interval &gt;450 ms)&#xD;
&#xD;
          -  A history of additional risk factors for Torsades de points (TdP) (e.g., heart&#xD;
             failure, hypokalemia, family history of Long QT Syndrome)&#xD;
&#xD;
        Exclusion criteria specific for this study:&#xD;
&#xD;
          -  Anemia at screening&#xD;
&#xD;
          -  Galactose intolerance&#xD;
&#xD;
          -  Lactase deficiency&#xD;
&#xD;
          -  Glucose-galactose-malabsorption&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.28_U09-1674-04.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 4, 2014</study_first_submitted>
  <study_first_submitted_qc>July 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 8, 2014</study_first_posted>
  <last_update_submitted>July 4, 2014</last_update_submitted>
  <last_update_submitted_qc>July 4, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 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>Linagliptin</mesh_term>
    <mesh_term>Warfarin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02183389
org study id: 1218.28
nct id: NCT02183389
lead sponsor: 
To investigate whether and to what extent BI 1356 affects pharmacokinetic and pharmacodynamic
      parameters of warfarin
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
time frame: Up to 168 hours after start of study medication
measure: Maximum measured concentration of the analyte in plasma (Cmax)
time frame: Up to 168 hours after start of study medication
measure: Area under the concentration time curve (AUC) of the analyte in plasma at different time points
time frame: Up to 168 hours after start of study medication
measure: Time from dosing to the maximum concentration of the analyte in plasma (tmax)
time frame: Up to 168 hours after start of study medication
measure: Terminal rate constant in plasma (λz)
time frame: Up to 168 hours after start of study medication
measure: Terminal half life of the analyte in plasma (t1/2)
time frame: Up to 168 hours after start of study medication
measure: Mean residence time of the analyte in the body after p.o. administration (MRTpo)
time frame: Up to 168 hours after start of study medication
measure: Apparent clearance of the analyte in the plasma after extravascular administration (CL/F)
time frame: Up to 168 hours after start of study medication
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
time frame: Up to 168 hours after start of study medication
measure: Number of patients with adverse events
time frame: Up 42 days
measure: Number of patients with relevant changes in physical examination
time frame: Up to 14 days after last study drug administration
measure: Number of patients with relevant changes in vital signs (Blood Pressure (BP), Pulse Rate (PR))
time frame: Up to 14 days after last study drug administration
measure: Number of patients with relevant changes in 12-lead resting electrocardiogram (ECG)
time frame: Up to 14 days after last study drug administration
measure: Number of patients with relevant changes in laboratory values
time frame: Up to 14 days after last study drug administration
measure: Assessment of tolerability a 4-point scale by the investigator
time frame: Up 42 days
measure: International normalised ratio, area under the concentration time curve of the analyte in plasma over the time interval from time zero to 168 hours (INR AUC0-168)
time frame: Up to 168 hours after start of treatment
measure: International normalised ratio, maximum concentration of the analyte in plasma (INRmax)
time frame: Up to 168 hours after start of treatment
measure: Prothrombin time, area under the concentration time curve of the analyte in plasma over the time interval from time zero to 168 hours (PT AUC0-168)
time frame: Up to 168 hours after start of treatment
measure: Prothrombin time, maximum concentration of the analyte in plasma (PTmax)
time frame: Up to 168 hours after start of treatment
arm group label: Treatment B: BI 1356 and Warfarin
arm group type: Experimental
description: BI 1356 for 12 days combined with a single dose of warfarin on day 6
arm group label: Treatment A: Warfarin
arm group type: Active Comparator
description: Warfarin as single dose
intervention type: Drug
intervention name: Warfarin
arm group label: Treatment A: Warfarin
arm group label: Treatment B: BI 1356 and Warfarin
intervention type: Drug
intervention name: BI 1356
arm group label: Treatment B: BI 1356 and Warfarin
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.28_U09-1674-04.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Linagliptin
mesh term: Warfarin