<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/NCT02183441</url>
  </required_header>
  <id_info>
    <org_study_id>1218.31</org_study_id>
    <nct_id>NCT02183441</nct_id>
  </id_info>
  <brief_title>Bioavailability of BI 1356 After Co-administration With Ritonavir Compared to the Bioavailability of BI 1356 Alone in Healthy Male Volunteers</brief_title>
  <official_title>Relative Bioavailability of a Single Oral Dose of BI 1356 (5 mg) After Co-administration With Multiple Oral Doses of Ritonavir (200 mg Bid for 3 Days) Compared to the Bioavailability of a Single Oral Dose of BI 1356 (5 mg) Alone in Healthy Male Volunteers (an Open-label, Randomized, Two-way Crossover, 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>
      Study to investigate the effect of the P-gp and cytochrome P450 (CYP) 3A4 inhibitor ritonavir&#xD;
      on the pharmacokinetics of BI 1356&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2008</start_date>
  <primary_completion_date type="Actual">June 2008</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>AUC0-24 (Area under the concentration-time curve of BI 1356 in plasma over the time interval from 0 to 24 hours)</measure>
    <time_frame>up to 24 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (Maximum measured concentration of BI 1356 in plasma)</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC (Area under the concentration time curve of the analytes in plasma at different time points)</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>%AUCtz-∞ (Percentage of the extrapolated part of the area under the concentration time curve of the analytes in plasma from 0 to infinity)</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (Time from dosing to the maximum concentration of the analytes in plasma)</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (Terminal half-life of the analytes in plasma)</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (Terminal rate constant of the analytes in plasma)</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo (Mean residence time in the body after po administration of the analytes in plasma)</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (Apparent clearance of BI 1356 in plasma after extravascular administration )</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) of BI 1356</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aet1-t2 (Amount of the analytes that is eliminated in urine from the time interval t1 to t2)</measure>
    <time_frame>up to 24 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fet1-t2 (Fraction of BI 1356 excreted unchanged in urine from time point t1 to t2)</measure>
    <time_frame>up to 24 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR,t1-t2 (Renal clearance of the analytes in plasma)</measure>
    <time_frame>up to 24 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (Maximum measured concentration of CD 1750 in Plasma)</measure>
    <time_frame>up to 96 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 53 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BI 1356 plus ritonavir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A: 3 days of ritonavir, 1 day BI 1356</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 1356</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment B: BI 1356 alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1356</intervention_name>
    <arm_group_label>BI 1356</arm_group_label>
    <arm_group_label>BI 1356 plus ritonavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>BI 1356 plus ritonavir</arm_group_label>
    <other_name>Norvir®</other_name>
  </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;
          -  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;
        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 (e.g. HIV)&#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 five half-lives of the respective drug prior to administration or during the&#xD;
             trial&#xD;
&#xD;
          -  Use of drugs which might reasonably influence the results of the trial (especially&#xD;
             unspecific inducing agents like St.John´s wort (Hypericum perforatum) or drugs which&#xD;
             prolong the QT/QTc interval based on the knowledge at the time of protocol preparation&#xD;
             within 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) or inability to stop alcoholic beverages for 24&#xD;
             hours prior to dosing and up to the last sampling time point&#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 (e.g., heart failure,&#xD;
             hypokalemia, family history of Long QT Syndrome)&#xD;
&#xD;
        Exclusion criteria specific for this study:&#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/1218/1218.31_U09-1077-01.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>Ritonavir</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/NCT02183441
org study id: 1218.31
nct id: NCT02183441
lead sponsor: 
Study to investigate the effect of the P-gp and cytochrome P450 (CYP) 3A4 inhibitor ritonavir
      on the pharmacokinetics of BI 1356
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-24 (Area under the concentration-time curve of BI 1356 in plasma over the time interval from 0 to 24 hours)
time frame: up to 24 hours after start of treatment
measure: Cmax (Maximum measured concentration of BI 1356 in plasma)
time frame: up to 96 hours after start of treatment
measure: AUC (Area under the concentration time curve of the analytes in plasma at different time points)
time frame: up to 96 hours after start of treatment
measure: %AUCtz-∞ (Percentage of the extrapolated part of the area under the concentration time curve of the analytes in plasma from 0 to infinity)
time frame: up to 96 hours after start of treatment
measure: tmax (Time from dosing to the maximum concentration of the analytes in plasma)
time frame: up to 96 hours after start of treatment
measure: t1/2 (Terminal half-life of the analytes in plasma)
time frame: up to 96 hours after start of treatment
measure: λz (Terminal rate constant of the analytes in plasma)
time frame: up to 96 hours after start of treatment
measure: MRTpo (Mean residence time in the body after po administration of the analytes in plasma)
time frame: up to 96 hours after start of treatment
measure: CL/F (Apparent clearance of BI 1356 in plasma after extravascular administration )
time frame: up to 96 hours after start of treatment
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) of BI 1356
time frame: up to 96 hours after start of treatment
measure: Aet1-t2 (Amount of the analytes that is eliminated in urine from the time interval t1 to t2)
time frame: up to 24 hours after start of treatment
measure: fet1-t2 (Fraction of BI 1356 excreted unchanged in urine from time point t1 to t2)
time frame: up to 24 hours after start of treatment
measure: CLR,t1-t2 (Renal clearance of the analytes in plasma)
time frame: up to 24 hours after start of treatment
measure: Cmax (Maximum measured concentration of CD 1750 in Plasma)
time frame: up to 96 hours after start of treatment
measure: Number of patients with adverse events
time frame: up to 53 days
arm group label: BI 1356 plus ritonavir
arm group type: Experimental
description: Treatment A: 3 days of ritonavir, 1 day BI 1356
arm group label: BI 1356
arm group type: Active Comparator
description: Treatment B: BI 1356 alone
intervention type: Drug
intervention name: BI 1356
arm group label: BI 1356
arm group label: BI 1356 plus ritonavir
intervention type: Drug
intervention name: Ritonavir
arm group label: BI 1356 plus ritonavir
other name: Norvir®
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/1218/1218.31_U09-1077-01.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Linagliptin
mesh term: Ritonavir