<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/NCT02243553</url>
  </required_header>
  <id_info>
    <org_study_id>1182.101</org_study_id>
    <nct_id>NCT02243553</nct_id>
  </id_info>
  <brief_title>Effects of Tipranavir (With Ritonavir) Capsule and Liquid Formulation on Cytochrome P450 and P-glycoprotein Activity in Healthy Volunteers</brief_title>
  <official_title>Evaluating the Effects of Tipranavir (With Ritonavir) Capsule and Liquid Formulation on Cytochrome P450 and P-glycoprotein Activity Using a Biomarker Cocktail in Healthy Human Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Primary: To quantify the influence of single-dose and steady-state tipranavir/ritonavir&#xD;
      500/200 mg on intestinal and hepatic cytochrome P450 (CYP) and P-glycoprotein (P-gp)&#xD;
      biomarkers, as a means of predicting drug interactions. The AUCs for biomarkers caffeine,&#xD;
      warfarin, omeprazole, dextromethorphan, midazolam, and digoxin will be assessed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2006</start_date>
  <primary_completion_date type="Actual">July 2006</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under plasma concentration-time curve (AUC) at steady state</measure>
    <time_frame>up to 72 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration after 12 hours (Cp12h)</measure>
    <time_frame>12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>up to 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum concentration (Tmax)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half-life (t1/2)</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under plasma concentration-time curve (AUC) after single dose</measure>
    <time_frame>up to 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in biomarkers</measure>
    <time_frame>baseline, up to 22 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in enzyme activity</measure>
    <time_frame>baseline, up to 22 days</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TPV capsule + RTV capsule + cocktail + digoxin injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TPV solution + RTV capsule + cocktail + digoxin oral</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TPV solution + RTV capsule + cocktail + digoxin injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir capsule</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir solution</intervention_name>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir capsule</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Caffeine</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin sodium</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin K</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextromethorphan hydrobromide</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam injection</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam oral solution</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin tablet</intervention_name>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Digoxin injection</intervention_name>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent&#xD;
&#xD;
          2. Healthy subjects aged between 18 years and 45 years inclusive&#xD;
&#xD;
          3. Weighing at least 50 kg&#xD;
&#xD;
          4. Volunteers must be hospitalized on Days 1-4, 7-9, and 17-20 for pharmacokinetic&#xD;
             assessments for each biomarker and TPV/r (Days 7-9 and 17-20)&#xD;
&#xD;
          5. Volunteers must be willing to complete all study-related activities&#xD;
&#xD;
          6. Each volunteer must have a valid social security number&#xD;
&#xD;
          7. Each volunteer must have acceptable medical history, physical examination and&#xD;
             laboratory test&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History or presence of allergy to the study drugs or their components or drugs of&#xD;
             their class, or a history of drug or other allergy that, in the opinion of the&#xD;
             physician responsible, contraindicates their participation&#xD;
&#xD;
          2. Any finding of the medical examination (including blood pressure, pulse rate and&#xD;
             electrocardiogram) deviating from normal and of clinical relevance&#xD;
&#xD;
          3. History or diagnosis of any significant medical conditions: Including but not limited&#xD;
             to gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunologic, hematological, psychiatric, neurological, oncological or hormonal&#xD;
             disorders&#xD;
&#xD;
          4. Known elevated liver enzymes in past clinical trials with any compound (experimental&#xD;
             or marketed)&#xD;
&#xD;
          5. Clinically relevant laboratory abnormalities (e.g. Hgb&lt;11g/dL, Hct&lt;30g/dL, total&#xD;
             cholesterol &gt;240mg/dL, triglycerides &gt;500mg/dL, fasting glucose &gt;130mg/dL, liver&#xD;
             function tests &gt;2.5x upper limit of normal, baseline international normalized ratio&#xD;
             &gt;1.2)&#xD;
&#xD;
          6. History of evidence of clinically significant hepatic, cardiac, pulmonary, endocrine,&#xD;
             immunological, gastrointestinal, hematological, vascular or collagen disease&#xD;
&#xD;
          7. History of alcohol abuse or use of any illicit drugs&#xD;
&#xD;
          8. Unable to abstain from more than one beer or alcohol equivalent per day for the&#xD;
             duration of the study&#xD;
&#xD;
          9. Use of tobacco products and/or history of smoking within the past 2 months&#xD;
&#xD;
         10. Pregnant or breast feeding&#xD;
&#xD;
         11. Sexually active women of childbearing age who do not use an acceptable barrier method&#xD;
             of birth control&#xD;
&#xD;
         12. Hypersensitivity to caffeine, warfarin, vitamin K, omeprazole, dextromethorphan,&#xD;
             midazolam, tipranavir, ritonavir or their excipients&#xD;
&#xD;
         13. Concomitant treatment with other experimental compounds&#xD;
&#xD;
         14. Concomitant administration of any prescription or over the counter medications known&#xD;
             to alter P450 enzyme or P-gp activity&#xD;
&#xD;
         15. Concomitant administration of any prescription or over the counter medications known&#xD;
             to be highly dependent on P450 or P-gp for clearance for which elevated plasma&#xD;
             concentrations are known to be associated with serious toxicity&#xD;
&#xD;
         16. Concomitant administration of any food product known to alter P450 enzyme or P-gp&#xD;
             activity such as grapefruit juice, Seville oranges&#xD;
&#xD;
         17. Concomitant administration of any drug that could affect bleeding (e.g., aspirin,&#xD;
             clopidogrel, ticlopidine, warfarin, heparin, low-molecular weight heparin)&#xD;
&#xD;
         18. Concomitant administration of oral contraceptives (may be included with 7-day washout&#xD;
             period)&#xD;
&#xD;
         19. Concomitant administration of any herbal medications&#xD;
&#xD;
         20. Inadequate venous access&#xD;
&#xD;
         21. Renal or hepatic insufficiency&#xD;
&#xD;
         22. Clinically unacceptable result at the screening physical examination&#xD;
&#xD;
         23. Use of investigational medications within 30 days before study entry&#xD;
&#xD;
         24. HIV-positive&#xD;
&#xD;
         25. Body Mass Index (BMI) &gt; 30 kg/m²&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 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>August 2014</verification_date>
  <study_first_submitted>September 1, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2014</study_first_posted>
  <last_update_submitted>September 16, 2014</last_update_submitted>
  <last_update_submitted_qc>September 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 18, 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>Vitamin K</mesh_term>
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Tipranavir</mesh_term>
    <mesh_term>Digoxin</mesh_term>
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Dextromethorphan</mesh_term>
    <mesh_term>Caffeine</mesh_term>
    <mesh_term>Omeprazole</mesh_term>
    <mesh_term>Warfarin</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/NCT02243553
org study id: 1182.101
nct id: NCT02243553
lead sponsor: 
Primary: To quantify the influence of single-dose and steady-state tipranavir/ritonavir
      500/200 mg on intestinal and hepatic cytochrome P450 (CYP) and P-glycoprotein (P-gp)
      biomarkers, as a means of predicting drug interactions. The AUCs for biomarkers caffeine,
      warfarin, omeprazole, dextromethorphan, midazolam, and digoxin will be assessed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under plasma concentration-time curve (AUC) at steady state
time frame: up to 72 hours
measure: Plasma concentration after 12 hours (Cp12h)
time frame: 12 hours
measure: Maximum plasma concentration (Cmax)
time frame: up to 12 hours
measure: Time of maximum concentration (Tmax)
time frame: up to 72 hours
measure: Apparent terminal half-life (t1/2)
time frame: up to 72 hours
measure: Area under plasma concentration-time curve (AUC) after single dose
time frame: up to 72 hours
measure: Change in biomarkers
time frame: baseline, up to 22 days
measure: Change in enzyme activity
time frame: baseline, up to 22 days
arm group label: Treatment A
arm group type: Experimental
description: tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
arm group label: Treatment B
arm group type: Experimental
description: TPV capsule + RTV capsule + cocktail + digoxin injection
arm group label: Treatment C
arm group type: Experimental
description: TPV solution + RTV capsule + cocktail + digoxin oral
arm group label: Treatment D
arm group type: Experimental
description: TPV solution + RTV capsule + cocktail + digoxin injection
intervention type: Drug
intervention name: Tipranavir capsule
arm group label: Treatment A
arm group label: Treatment B
intervention type: Drug
intervention name: Tipranavir solution
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Ritonavir capsule
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Caffeine
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Warfarin sodium
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Vitamin K
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Omeprazole
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Dextromethorphan hydrobromide
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Midazolam injection
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Midazolam oral solution
arm group label: Treatment A
arm group label: Treatment B
arm group label: Treatment C
arm group label: Treatment D
intervention type: Drug
intervention name: Digoxin tablet
arm group label: Treatment A
arm group label: Treatment C
intervention type: Drug
intervention name: Digoxin injection
arm group label: Treatment B
arm group label: Treatment D
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Vitamin K
mesh term: Ritonavir
mesh term: Tipranavir
mesh term: Digoxin
mesh term: Midazolam
mesh term: Dextromethorphan
mesh term: Caffeine
mesh term: Omeprazole
mesh term: Warfarin
mesh term: Pharmaceutical Solutions