<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/NCT02183506</url>
  </required_header>
  <id_info>
    <org_study_id>1218.4</org_study_id>
    <nct_id>NCT02183506</nct_id>
  </id_info>
  <brief_title>Bioavailability of BI 1356 BS and Metformin After Co-administration Compared to the Bioavailability of BI 1356 BS Alone and Metformin Alone in Healthy Male Volunteers</brief_title>
  <official_title>Bioavailability of Both BI 1356 BS and Metformin After Co-administration Compared to the Bioavailability of Multiple Oral Doses of BI 1356 BS 10 mg Daily Alone and Metformin 850 mg Three Times a Day Alone in Healthy Male Volunteers (an Open-label, Randomized, Crossover 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>
      Investigate the bioavailability of BI 1356 BS and of metformin after concomitant multiple&#xD;
      oral administration of 10 mg BI 1356 BS tablets and 3 x 850 mg metformin in comparison to BI&#xD;
      1356 BS and metformin given alone&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2005</start_date>
  <primary_completion_date type="Actual">December 2005</primary_completion_date>
  <phase>Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the concentration-time curve (AUC) of the analytes in plasma at different time points</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum concentration (Cmax) of the analytes in plasma at different time points</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time from last dosing to maximum concentration of the analytes in plasma at steady state (tmax,ss)</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum concentration of the analytes in plasma at steady state (Cmin,ss) over a uniform dosing interval τ</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant of the analytes in plasma at steady state (λz,ss )</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life of the analytes in plasma at steady state (t1/2,ss )</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of the analytes in the body at steady state after oral administration (MRTpo,ss)</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance of the analytes in the plasma at steady state (CL/F,ss) following extravascular multiple dose administration</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz at steady state (Vz/F,ss) following extravascular administration</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurements of dipeptidylpeptidase 4 (DPP-IV) activity</measure>
    <time_frame>up to 240 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 60 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically abnormal changes in laboratory values</measure>
    <time_frame>Baseline, up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in vital signs</measure>
    <time_frame>Baseline, up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>feτ,ss (fraction of the dose excreted unchanged in urine at steady state)</measure>
    <time_frame>0-4 h, 4-8 h, 8-12 h and 12-24 hours after drug administration on days 3, 6, 9</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR,ss (renal clearance of the analyte in plasma at steady state)</measure>
    <time_frame>0-4 h, 4-8 h, 8-12 h and 12-24 hours after drug administration on days 3, 6, 9</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 1356 BS and metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily administration of BI 1356 BS alone (day 1 to day 6) followed by the combined treatment of BI 1356 BS with metformin (day 7 to day 9)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <arm_group_label>BI 1356 BS and metformin</arm_group_label>
    <arm_group_label>Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1356 BS</intervention_name>
    <arm_group_label>BI 1356 BS and metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males according to the following criteria, based upon a complete medical&#xD;
             history, including the physical examination, vital signs (blood pressure (BP), pulse&#xD;
             rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests&#xD;
&#xD;
               -  No finding deviating from normal and of clinical relevance&#xD;
&#xD;
               -  No evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Age ≥ 21 and Age ≤ 50 years&#xD;
&#xD;
          -  BMI (Body Mass Index) ≥ 18.5 and ≤ 29.9 kg/m2&#xD;
&#xD;
          -  Ability to give signed and dated written informed consent prior to admission to the&#xD;
             study in accordance with good clinical practice (GCP) and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#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 allergy/hypersensitivity (including drug allergy) which is deemed relevant&#xD;
             to the trial by the investigator&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt;24 hours) within one month or less than 10&#xD;
             half-lives of the respective drug prior to administration or during the conduct of&#xD;
             this trial (review with clinical monitor if there is a question)&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial (based on&#xD;
             knowledge at the time of protocol preparation) within 10 days prior to administration&#xD;
             or during the conduct of this trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within two months prior to&#xD;
             administration or during the conduct of this trial&#xD;
&#xD;
          -  Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)&#xD;
&#xD;
          -  Inability to refrain from smoking during the conduct of this trial&#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 conduct of this trial)&#xD;
&#xD;
          -  Excessive physical activities (within one week prior to administration or during the&#xD;
             conduct of this trial)&#xD;
&#xD;
          -  Any laboratory value outside the normal reference range that is of clinical relevance&#xD;
&#xD;
          -  Inability to comply with the dietary regimen of the study center&#xD;
&#xD;
          -  No adequate contraception (condom use plus another form of contraception e.g.,&#xD;
             spermicide, oral contraceptive taken by female partner, sterilization) during the&#xD;
             whole study period from the time of the first intake of study drug until one month&#xD;
             after the last intake of drug&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 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/1218/1218.4_U06-3414.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>Metformin</mesh_term>
    <mesh_term>Linagliptin</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/NCT02183506
org study id: 1218.4
nct id: NCT02183506
lead sponsor: 
Investigate the bioavailability of BI 1356 BS and of metformin after concomitant multiple
      oral administration of 10 mg BI 1356 BS tablets and 3 x 850 mg metformin in comparison to BI
      1356 BS and metformin given alone
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the concentration-time curve (AUC) of the analytes in plasma at different time points
time frame: up to 240 hours after start of treatment
measure: Maximum concentration (Cmax) of the analytes in plasma at different time points
time frame: up to 240 hours after start of treatment
measure: Time from last dosing to maximum concentration of the analytes in plasma at steady state (tmax,ss)
time frame: up to 240 hours after start of treatment
measure: Minimum concentration of the analytes in plasma at steady state (Cmin,ss) over a uniform dosing interval τ
time frame: up to 240 hours after start of treatment
measure: Terminal rate constant of the analytes in plasma at steady state (λz,ss )
time frame: up to 240 hours after start of treatment
measure: Terminal half-life of the analytes in plasma at steady state (t1/2,ss )
time frame: up to 240 hours after start of treatment
measure: Mean residence time of the analytes in the body at steady state after oral administration (MRTpo,ss)
time frame: up to 240 hours after start of treatment
measure: Apparent clearance of the analytes in the plasma at steady state (CL/F,ss) following extravascular multiple dose administration
time frame: up to 240 hours after start of treatment
measure: Apparent volume of distribution during the terminal phase λz at steady state (Vz/F,ss) following extravascular administration
time frame: up to 240 hours after start of treatment
measure: Measurements of dipeptidylpeptidase 4 (DPP-IV) activity
time frame: up to 240 hours after start of treatment
measure: Number of patients with adverse events
time frame: up to 60 days
measure: Number of patients with clinically abnormal changes in laboratory values
time frame: Baseline, up to 14 days after last drug administration
measure: Number of patients with clinically relevant changes in vital signs
time frame: Baseline, up to 14 days after last drug administration
measure: feτ,ss (fraction of the dose excreted unchanged in urine at steady state)
time frame: 0-4 h, 4-8 h, 8-12 h and 12-24 hours after drug administration on days 3, 6, 9
measure: CLR,ss (renal clearance of the analyte in plasma at steady state)
time frame: 0-4 h, 4-8 h, 8-12 h and 12-24 hours after drug administration on days 3, 6, 9
arm group label: Metformin
arm group type: Active Comparator
arm group label: BI 1356 BS and metformin
arm group type: Experimental
description: Daily administration of BI 1356 BS alone (day 1 to day 6) followed by the combined treatment of BI 1356 BS with metformin (day 7 to day 9)
intervention type: Drug
intervention name: Metformin
arm group label: BI 1356 BS and metformin
arm group label: Metformin
intervention type: Drug
intervention name: BI 1356 BS
arm group label: BI 1356 BS and metformin
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.4_U06-3414.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Metformin
mesh term: Linagliptin