<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/NCT02253797</url>
  </required_header>
  <id_info>
    <org_study_id>1182.24</org_study_id>
    <nct_id>NCT02253797</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Tipranavir/Ritonavir and Its Metabolites in Healthy Male Subjects</brief_title>
  <official_title>A Phase I Multiple Oral Dose Trial of Tipranavir 500 mg/Ritonavir 200 mg Dosed to Steady State Followed by Single-dose 14C-radiolabeled Tipranavir Co-administered With Tipranavir 500 mg/Ritonavir 200 mg to Characterize the Excretion Balance and Metabolite Profile of 14C-radiolabeled Tipranavir in Healthy Male Subjects</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 evaluate the pharmacokinetics of Tipranavir and its metabolites including excretion&#xD;
      and mass balance of parent compound and radioactivity at steady-state; to isolate, identify&#xD;
      and quantify major metabolites of tipranavir in plasma, urine and feces&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2003</start_date>
  <primary_completion_date type="Actual">July 2003</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>Radioactive levels of 14C-Tipranavir in plasma and blood</measure>
    <time_frame>-10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Radioactive erythrocyte-plasma partition ratio</measure>
    <time_frame>-10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum measured concentration of the analyte in plasma (Cmax)</measure>
    <time_frame>-10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration</time_frame>
    <description>14C-radiolabeled Tipranavir + Tipranavir</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentration 12 hours after dosing (Cp12h)</measure>
    <time_frame>-10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration</time_frame>
    <description>14C-radiolabeled Tipranavir + Tipranavir</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under plasma concentration time curve (AUC)</measure>
    <time_frame>-10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration</time_frame>
    <description>14C-radiolabeled Tipranavir + Tipranavir</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of maximum concentration (Tmax)</measure>
    <time_frame>-10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration</time_frame>
    <description>14C-radiolabeled Tipranavir + Tipranavir</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent terminal half life (t1/2)</measure>
    <time_frame>-10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration</time_frame>
    <description>14C-radiolabeled Tipranavir + Tipranavir</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative amount of 14C- radioactivity in Urine and feces</measure>
    <time_frame>up to 15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent excretion in urine and feces</measure>
    <time_frame>up to 15 days</time_frame>
    <description>relative to total radioactivity administered</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time needed to achieve steady-state as determined by tipranavir trough concentrations</measure>
    <time_frame>up to 15 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal changes in laboratory parameters</measure>
    <time_frame>up to day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant changes in Electrocardiogram (ECG)</measure>
    <time_frame>up to day 6</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV/r followed by 14C-radiolabeled TPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tipranavir/Ritonavir dosed to steady state followed by single-dose 14C-radiolabeled tipranavir co-administered with Tipranavir/Ritonavir</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>14C-Tipranavir</intervention_name>
    <arm_group_label>TPV/r followed by 14C-radiolabeled TPV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <arm_group_label>TPV/r followed by 14C-radiolabeled TPV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>TPV/r followed by 14C-radiolabeled TPV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy HIV-negative male subjects as determined by results of screening. Healthiness&#xD;
             was determined by medical history, laboratory testing and 12-lead ECG&#xD;
&#xD;
          2. Signed written informed consent in accordance with Good Clinical Practice (GCP)&#xD;
&#xD;
          3. Age &gt;18 and &lt;=60 years&#xD;
&#xD;
          4. Subjects within 20% of the normal height: weight range defined by the Metropolitan&#xD;
             Life Insurance Company Tables&#xD;
&#xD;
          5. Ability to swallow numerous large capsules&#xD;
&#xD;
          6. Willingness to abstain from smoking, ingesting methylxanthine containing drinks or&#xD;
             food (coffee, tea, cola, chocolate, etc.), or ingesting alcohol, St. John's Wort, milk&#xD;
             thistle, garlic supplements, Seville oranges, and grapefruit or grapefruit juice for&#xD;
             the duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any finding of the medical examination (including blood pressure, pulse rate, and ECG)&#xD;
             deviating from normal and of clinical relevance&#xD;
&#xD;
          2. History of clinically significant disease including metabolic, endocrinologic,&#xD;
             immunological, hepatic, renal, gastrointestinal, respiratory, cardiovascular,&#xD;
             psychiatric or neurological&#xD;
&#xD;
          3. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant&#xD;
             to the trial as judged by the investigator and/or the sponsor&#xD;
&#xD;
          4. Subjects with a history of drug abuse or alcoholism&#xD;
&#xD;
          5. Chronic or relevant acute (within 2 weeks of screening) infections&#xD;
&#xD;
          6. Subjects who have taken prescription medications, over-the-counter drugs, or herbal&#xD;
             preparations within 2 weeks of the start of the trial&#xD;
&#xD;
          7. Participation in another trial with an investigational drug (in the 30 days prior to&#xD;
             screening)&#xD;
&#xD;
          8. Blood donation &gt;400 mL (within 1 month prior to treatment administration or during the&#xD;
             trial)&#xD;
&#xD;
          9. Any laboratory value that represents a Division of DAIDS (DAIDS) toxicity Grade &gt;1&#xD;
&#xD;
         10. Positive urine drug screen, positive HIV antibody, positive Hepatitis C Ribonucleic&#xD;
             acid (RNA), or positive Hepatitis B surface antigen&#xD;
&#xD;
         11. History of any familial bleeding disorder&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>September 29, 2014</last_update_submitted>
  <last_update_submitted_qc>September 29, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 1, 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>Ritonavir</mesh_term>
    <mesh_term>Tipranavir</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/NCT02253797
org study id: 1182.24
nct id: NCT02253797
lead sponsor: 
Study to evaluate the pharmacokinetics of Tipranavir and its metabolites including excretion
      and mass balance of parent compound and radioactivity at steady-state; to isolate, identify
      and quantify major metabolites of tipranavir in plasma, urine and feces
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Radioactive levels of 14C-Tipranavir in plasma and blood
time frame: -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration
measure: Radioactive erythrocyte-plasma partition ratio
time frame: -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration
measure: Maximum measured concentration of the analyte in plasma (Cmax)
time frame: -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration
description: 14C-radiolabeled Tipranavir + Tipranavir
measure: Plasma concentration 12 hours after dosing (Cp12h)
time frame: -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration
description: 14C-radiolabeled Tipranavir + Tipranavir
measure: Area under plasma concentration time curve (AUC)
time frame: -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration
description: 14C-radiolabeled Tipranavir + Tipranavir
measure: Time of maximum concentration (Tmax)
time frame: -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration
description: 14C-radiolabeled Tipranavir + Tipranavir
measure: Apparent terminal half life (t1/2)
time frame: -10 minutes, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dose administration
description: 14C-radiolabeled Tipranavir + Tipranavir
measure: Cumulative amount of 14C- radioactivity in Urine and feces
time frame: up to 15 days
measure: Percent excretion in urine and feces
time frame: up to 15 days
description: relative to total radioactivity administered
measure: Time needed to achieve steady-state as determined by tipranavir trough concentrations
time frame: up to 15 days
measure: Number of subjects with adverse events
time frame: up to 15 days
measure: Number of subjects with abnormal changes in laboratory parameters
time frame: up to day 14
measure: Number of subjects with clinically significant changes in Electrocardiogram (ECG)
time frame: up to day 6
arm group label: TPV/r followed by 14C-radiolabeled TPV
arm group type: Experimental
description: Tipranavir/Ritonavir dosed to steady state followed by single-dose 14C-radiolabeled tipranavir co-administered with Tipranavir/Ritonavir
intervention type: Drug
intervention name: 14C-Tipranavir
arm group label: TPV/r followed by 14C-radiolabeled TPV
intervention type: Drug
intervention name: Tipranavir
arm group label: TPV/r followed by 14C-radiolabeled TPV
intervention type: Drug
intervention name: Ritonavir
arm group label: TPV/r followed by 14C-radiolabeled TPV
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Ritonavir
mesh term: Tipranavir