<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/NCT02183610</url>
  </required_header>
  <id_info>
    <org_study_id>1218.7</org_study_id>
    <nct_id>NCT02183610</nct_id>
  </id_info>
  <brief_title>Investigation of the Metabolism and Pharmacokinetics of 10 mg [14C] BI 1356 Administered Orally Compared to 5 mg [14C] BI 1356 Administered Intravenously in Healthy Male Volunteers</brief_title>
  <official_title>Investigation of the Metabolism and Pharmacokinetics of 10 mg [14C] BI 1356 Administered Orally Compared to 5 mg [14C] BI 1356 Administered Intravenously in Healthy Male Volunteers in an Open Label, Single-dose and Parallel Study Design</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 determine the basic pharmacokinetics of BI 1356 BS, its metabolite CD 1750 XX and&#xD;
      radioactivity including excretion mass balance, excretion pathways and metabolism following&#xD;
      the intravenous and oral administration of [14C] BI 1356 BS&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2006</start_date>
  <primary_completion_date type="Actual">September 2006</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of individual time course profiles of [14C] radioactivity in whole blood, plasma, urine and faeces</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Comparison of individual time course profiles of BI 1356 BS and its metabolite CD 1750 XX in plasma and urine</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate and extent of excretion mass balance based on the total radioactivity in urine and faeces</measure>
    <time_frame>prior to and up to 120 h after start of administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>CBlood cell/Cplasma ratio of [14C] -radioactivity</measure>
    <time_frame>1:30, 3, 24 and 72 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of the plasma protein binding of total [14C] radioactivity in human plasma samples ex vivo</measure>
    <time_frame>1:30 and 3 hours post drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum concentration of the analyte(s) in plasma)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>tmax (time from dosing to the maximum concentration of the analyte(s) in plasma)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-infinity (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to infinity)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>λz (terminal rate constant in plasma)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>t1/2 (terminal half-life of the analyte(s) in plasma)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>MRTpo and MRT, respectively (mean residence time of the analyte(s) in the body after p.o. and i.v. administration)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>CL/F (apparent/total clearance of the analyte(s) in plasma following extravascular and intravenous administration)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular or intravenous administration (F=1) respectively)</measure>
    <time_frame>before and up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>feurine,0-tz (amount of analyte excreted in urine within the time interval zero to tz (=120 h) in % of dose)</measure>
    <time_frame>prior to and up to 120 h after start of administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>fefaeces,0-tz (amount of analyte excreted in faeces within the time interval zero to tz (=120 h) in % of dose)</measure>
    <time_frame>up to 120 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>CLR,0-tz (renal clearance of analyte)</measure>
    <time_frame>prior to and up to 120 h after start of administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Fa (drug absorption based on radioactivity data)</measure>
    <time_frame>up to 264 h after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 47 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>on day 12 during ambulant visit or on day of discharge on day 13, 14 or 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of local tolerability of the infusion by investigator on a 6-point scale</measure>
    <time_frame>after start of infusion up to day 15</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>[14C] BI 1356 as oral (p.o.) solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>[14C] BI 1356 solution for i.v. infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14C] BI 1356 as oral (p.o.) solution</intervention_name>
    <arm_group_label>[14C] BI 1356 as oral (p.o.) solution</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14C] BI 1356 solution for i.v. infusion</intervention_name>
    <arm_group_label>[14C] BI 1356 solution for i.v. infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Healthy males according to the following criteria: Based upon a complete medical history,&#xD;
        including the physical examination, vital signs Blood Pressure (BP), Pulse Rate (PR)),&#xD;
        12-lead Electrocardiogram (ECG), clinical laboratory tests&#xD;
&#xD;
          -  Age &gt;=30 and Age &lt;=60 years&#xD;
&#xD;
          -  BMI &gt;=18.5 and BMI &lt;=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;
          -  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 based on the&#xD;
             knowledge at the time of protocol preparation within 10 days prior to administration&#xD;
             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 during the stay in the trial centre&#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 study centre&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a&#xD;
             QTc interval &gt;450 ms);&#xD;
&#xD;
          -  Male subjects must agree to minimize the risk of female partners becoming pregnant&#xD;
             from the dosing day until 3 months after the completion of the study. Acceptable&#xD;
             methods of contraception for male volunteers include a vasectomy no less than 3 months&#xD;
             prior to dosing, barrier contraception or a medically accepted contraceptive method.&#xD;
             For female partners of male volunteers, acceptable methods of contraception include&#xD;
             intra-uterine device, tubal ligation, hormonal contraceptive since at least two months&#xD;
             and diaphragm with spermicide&#xD;
&#xD;
        Exclusion criteria specific for this study:&#xD;
&#xD;
          -  Veins unsuitable for infusion and blood sampling&#xD;
&#xD;
          -  PR interval &gt;220 ms or QRS interval &gt;120 ms&#xD;
&#xD;
          -  Female gender&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 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/1218/1218.7_U08-1363-01.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 8, 2014</study_first_posted>
  <last_update_submitted>July 7, 2014</last_update_submitted>
  <last_update_submitted_qc>July 7, 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>Pharmaceutical Solutions</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/NCT02183610
org study id: 1218.7
nct id: NCT02183610
lead sponsor: 
To determine the basic pharmacokinetics of BI 1356 BS, its metabolite CD 1750 XX and
      radioactivity including excretion mass balance, excretion pathways and metabolism following
      the intravenous and oral administration of [14C] BI 1356 BS
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Comparison of individual time course profiles of [14C] radioactivity in whole blood, plasma, urine and faeces
time frame: before and up to 264 h after drug administration
measure: Comparison of individual time course profiles of BI 1356 BS and its metabolite CD 1750 XX in plasma and urine
time frame: before and up to 264 h after drug administration
measure: Rate and extent of excretion mass balance based on the total radioactivity in urine and faeces
time frame: prior to and up to 120 h after start of administration
measure: CBlood cell/Cplasma ratio of [14C] -radioactivity
time frame: 1:30, 3, 24 and 72 h after drug administration
measure: Measurement of the plasma protein binding of total [14C] radioactivity in human plasma samples ex vivo
time frame: 1:30 and 3 hours post drug administration
measure: Cmax (maximum concentration of the analyte(s) in plasma)
time frame: before and up to 264 h after drug administration
measure: tmax (time from dosing to the maximum concentration of the analyte(s) in plasma)
time frame: before and up to 264 h after drug administration
measure: AUC0-tz (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: before and up to 264 h after drug administration
measure: AUC0-infinity (area under the concentration-time curve of the analyte(s) in plasma over the time interval from 0 to infinity)
time frame: before and up to 264 h after drug administration
measure: λz (terminal rate constant in plasma)
time frame: before and up to 264 h after drug administration
measure: t1/2 (terminal half-life of the analyte(s) in plasma)
time frame: before and up to 264 h after drug administration
measure: MRTpo and MRT, respectively (mean residence time of the analyte(s) in the body after p.o. and i.v. administration)
time frame: before and up to 264 h after drug administration
measure: CL/F (apparent/total clearance of the analyte(s) in plasma following extravascular and intravenous administration)
time frame: before and up to 264 h after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular or intravenous administration (F=1) respectively)
time frame: before and up to 264 h after drug administration
measure: feurine,0-tz (amount of analyte excreted in urine within the time interval zero to tz (=120 h) in % of dose)
time frame: prior to and up to 120 h after start of administration
measure: fefaeces,0-tz (amount of analyte excreted in faeces within the time interval zero to tz (=120 h) in % of dose)
time frame: up to 120 h after drug administration
measure: CLR,0-tz (renal clearance of analyte)
time frame: prior to and up to 120 h after start of administration
measure: Fa (drug absorption based on radioactivity data)
time frame: up to 264 h after drug administration
measure: Number of patients with adverse events
time frame: up to 47 days
measure: Global assessment of tolerability by investigator on a 4-point scale
time frame: on day 12 during ambulant visit or on day of discharge on day 13, 14 or 15
measure: Evaluation of local tolerability of the infusion by investigator on a 6-point scale
time frame: after start of infusion up to day 15
arm group label: [14C] BI 1356 as oral (p.o.) solution
arm group type: Experimental
arm group label: [14C] BI 1356 solution for i.v. infusion
arm group type: Experimental
intervention type: Drug
intervention name: [14C] BI 1356 as oral (p.o.) solution
arm group label: [14C] BI 1356 as oral (p.o.) solution
intervention type: Drug
intervention name: [14C] BI 1356 solution for i.v. infusion
arm group label: [14C] BI 1356 solution for i.v. infusion
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1218/1218.7_U08-1363-01.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Linagliptin
mesh term: Pharmaceutical Solutions