<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/NCT02251145</url>
  </required_header>
  <id_info>
    <org_study_id>1182.46</org_study_id>
    <nct_id>NCT02251145</nct_id>
  </id_info>
  <brief_title>Effects of Tipranavir (TPV) and Ritonavir (RTV) on the Pharmacokinetic Characteristics of Tenofovir Disoproxil Fumarate in Healthy Volunteers</brief_title>
  <official_title>A Single Centre, Open-Label, Randomised, Parallel, Multiple Dose Comparison of the Effects of Tipranavir 500 mg and Ritonavir 100 mg or Tipranavir 750 mg and Ritonavir 200 mg Twice a Day for 11.5 Days on the Pharmacokinetic Characteristics of Tenofovir Disoproxil Fumarate 300 mg in Healthy 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>
      Study to characterise the effects of two dose combinations of tipranavir/ritonavir (TPV 500&#xD;
      mg/RTV 100 mg and TPV 750 mg/RTV 200 mg) administered BID, on the pharmacokinetics of&#xD;
      tenofovir disoproxil fumarate as well as the effects of tenofovir disoproxil fumarate on the&#xD;
      pharmacokinetics of tipranavir/ritonavir.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2002</start_date>
  <primary_completion_date type="Actual">June 2002</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 from 0-24 hours (AUC0-24) for tenofovir</measure>
    <time_frame>up to 24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under plasma concentration time curve from 0-12hours (AUC0-12) for tipranavir/ritonavir</measure>
    <time_frame>up to 12 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>up to 24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration in plasma at 12 hours after administration (C12h) for tenofovir</measure>
    <time_frame>up to 12 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration in plasma at 12 hours after administration (C12h) for tipranavir/ritonavir</measure>
    <time_frame>up to 12 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration at steady state (Cmax,ss)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough plasma concentration at steady state (Cmin)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residency time (MRT)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half life (T1/2)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum concentration (Tmax)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (CL/F)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal elimination phase, divided by F (bioavailability factor) (Vz/F)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in vital signs (pulse rate, blood pressure)</measure>
    <time_frame>up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in physical examination</measure>
    <time_frame>up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in electrocardiogram</measure>
    <time_frame>up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in laboratory tests</measure>
    <time_frame>up to 14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 14 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>tipranavir/ritonavir low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>tipranavir/ritonavir high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir low dose</intervention_name>
    <arm_group_label>tipranavir/ritonavir low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir high dose</intervention_name>
    <arm_group_label>tipranavir/ritonavir high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir low dose</intervention_name>
    <arm_group_label>tipranavir/ritonavir low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir high dose</intervention_name>
    <arm_group_label>tipranavir/ritonavir high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir disoproxil fumarate</intervention_name>
    <arm_group_label>tipranavir/ritonavir high dose</arm_group_label>
    <arm_group_label>tipranavir/ritonavir low dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability and willingness to give written informed consent in accordance with&#xD;
             institutional and regulatory guidelines and to comply with the investigational nature&#xD;
             of the study and the related requirements&#xD;
&#xD;
          2. Healthy males or females between 18 and 60 years of age inclusive&#xD;
&#xD;
          3. A Body Mass Index &gt;18.5 and &lt;30 kg/m2&#xD;
&#xD;
          4. Ability to swallow numerous large capsules without difficulty&#xD;
&#xD;
          5. Reasonable probability for completion of the study, in the opinion of the investigator&#xD;
&#xD;
          6. Acceptable laboratory values that indicate adequate baseline organ function are&#xD;
             required at the time of screening. Laboratory values are considered to be acceptable&#xD;
             if severity &lt;= Grade1 based on the AIDS Clinical Trials Group (ACTG) Division of AIDS&#xD;
             (DAIDS) Grading Scale. All abnormal laboratory values &gt; Grade 1 (e.g., creatine&#xD;
             phosphokinase (CPK), amylase, triglycerides) are subject to approval by the BIPI&#xD;
             clinical monitor. Cholesterol &lt;= 240mg/dL at the time of screening is necessary for&#xD;
             study entry&#xD;
&#xD;
          7. Acceptable medical history, physical examination and ECG are required prior to&#xD;
             entering the study&#xD;
&#xD;
          8. Willingness to abstain from alcohol for 48 hours prior to Study Day 0 and abstain from&#xD;
             alcohol for the duration of the study. In addition, Cabernet Sauvignon must not have&#xD;
             been ingested within 15 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          9. Willingness to abstain from ingesting grapefruit and grapefruit juice within 15 days&#xD;
             of Day 0, Visit 2 and for the duration of the study&#xD;
&#xD;
         10. Willingness to abstain from ingesting Seville oranges, strawberries or strawberry&#xD;
             extract, garlic supplements, St. John's Wort, Milk Thistle, or&#xD;
             methylxanthine-containing drinks or food (coffee, tea, cola, energy drinks, chocolate,&#xD;
             etc) within 72 hours of pharmacokinetic (PK) sampling days&#xD;
&#xD;
         11. Willingness to abstain from use of tobacco products for the duration of the study&#xD;
&#xD;
         12. Urine drug screen negative for illegal non-prescription drugs&#xD;
&#xD;
         13. Negative HIV serology&#xD;
&#xD;
         14. Negative for Hepatitis B surface antigen and Hepatitis C&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female subjects who are of reproductive potential who:&#xD;
&#xD;
               -  Have a positive serum B-HCG at Visit 1 or 2 or&#xD;
&#xD;
               -  Have not been using regular oral contraception (combined oestrogen and&#xD;
                  progestogen pill or progestogen only pill) for 3 months and a barrier&#xD;
                  contraceptive method for at least 30 days prior to Visit 3 (Day 1) or a barrier&#xD;
                  contraceptive method for at least 3 months prior to Visit 3 (Day 1) or&#xD;
&#xD;
               -  Are not willing to use a reliable method of double-barrier contraception (such as&#xD;
                  diaphragm with spermicidal cream/jelly or condoms with spermicidal foam)during&#xD;
                  the trial and 30 days after completion/termination or&#xD;
&#xD;
               -  Are breast-feeding&#xD;
&#xD;
          2. Participation in another trial with an investigational medicine for 30 days prior to&#xD;
             Day 0 (Visit 2)&#xD;
&#xD;
          3. Ingestion of any known enzyme altering drug (such as phenothiazines, cimetidine,&#xD;
             barbiturates, ketoconazole, fluconazole, rifampin, steroids, and herbal medications)&#xD;
             for 30 days prior to Day 0 (Visit 2). Use of any other herbal/complementary treatment&#xD;
             must be discussed in advance with the monitor and permission obtained prior to study&#xD;
             entry&#xD;
&#xD;
          4. Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within 15 days prior&#xD;
             to Day 0 (Visit 2)&#xD;
&#xD;
          5. Ingestion of Seville oranges, strawberries or strawberry extract, garlic supplements,&#xD;
             St. John's Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee,&#xD;
             tea, cola, energy drinks, chocolate, etc) within 72 hours of PK sampling days&#xD;
&#xD;
          6. Ingestion of antibiotics within 10 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          7. Inability to comply with investigator's instructions&#xD;
&#xD;
          8. History of gastrointestinal, hepatic, or renal disorders within 60 days&#xD;
&#xD;
          9. History of alcohol abuse&#xD;
&#xD;
         10. Current use of cigarettes defined as greater than 10 cigarettes per day or&#xD;
             rolling/pipe tobacco equivalent&#xD;
&#xD;
         11. Blood or plasma donations within 30 days prior to Day 0 (Visit 2)&#xD;
&#xD;
         12. Subjects with a seated systolic blood pressure either &lt;100 mm Hg or &gt;150 mm Hg;&#xD;
             resting heart rate either &lt;50 beats/min or &gt;100 beats/min&#xD;
&#xD;
         13. Subjects with a history of any illness or allergy that, in the opinion of the&#xD;
             investigator, might confound the results of the study or pose additional risk in&#xD;
             administering tipranavir or ritonavir or tenofovir disoproxil fumarate to the subject&#xD;
&#xD;
         14. Subjects who have had an acute illness within 2 weeks prior to Day 0 (Visit 2)&#xD;
&#xD;
         15. Subjects who are currently taking any over-the-counter drug within 7 days prior to Day&#xD;
             0, (Visit 2) or who are currently taking any prescription drug that, in the opinion of&#xD;
             the investigator in consultation with the clinical monitor and pharmacokineticist,&#xD;
             might interfere with either the absorption, distribution or metabolism of the test&#xD;
             substances&#xD;
&#xD;
         16. Hypersensitivity to tipranavir, ritonavir, or tenofovir disoproxil fumarate&#xD;
      </textblock>
    </criteria>
    <gender>All</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 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>September 25, 2014</last_update_submitted>
  <last_update_submitted_qc>September 25, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 29, 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>Tenofovir</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/NCT02251145
org study id: 1182.46
nct id: NCT02251145
lead sponsor: 
Study to characterise the effects of two dose combinations of tipranavir/ritonavir (TPV 500
      mg/RTV 100 mg and TPV 750 mg/RTV 200 mg) administered BID, on the pharmacokinetics of
      tenofovir disoproxil fumarate as well as the effects of tenofovir disoproxil fumarate on the
      pharmacokinetics of tipranavir/ritonavir.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under plasma concentration time curve from 0-24 hours (AUC0-24) for tenofovir
time frame: up to 24 hours
measure: Area under plasma concentration time curve from 0-12hours (AUC0-12) for tipranavir/ritonavir
time frame: up to 12 hours
measure: Maximum plasma concentration (Cmax)
time frame: up to 24 hours
measure: Drug concentration in plasma at 12 hours after administration (C12h) for tenofovir
time frame: up to 12 hours
measure: Drug concentration in plasma at 12 hours after administration (C12h) for tipranavir/ritonavir
time frame: up to 12 hours
measure: Maximum plasma concentration at steady state (Cmax,ss)
time frame: up to 24 hours
measure: Trough plasma concentration at steady state (Cmin)
time frame: up to 24 hours
measure: Mean residency time (MRT)
time frame: up to 24 hours
measure: Apparent terminal half life (T1/2)
time frame: up to 24 hours
measure: Time of maximum concentration (Tmax)
time frame: up to 24 hours
measure: Oral clearance (CL/F)
time frame: up to 24 hours
measure: Apparent volume of distribution during the terminal elimination phase, divided by F (bioavailability factor) (Vz/F)
time frame: up to 24 hours
measure: Number of subjects with clinically significant findings in vital signs (pulse rate, blood pressure)
time frame: up to 14 days
measure: Number of subjects with clinically significant findings in physical examination
time frame: up to 14 days
measure: Number of subjects with clinically significant findings in electrocardiogram
time frame: up to 14 days
measure: Number of subjects with clinically significant findings in laboratory tests
time frame: up to 14 days
measure: Number of subjects with adverse events
time frame: up to 14 days
arm group label: tipranavir/ritonavir low dose
arm group type: Experimental
arm group label: tipranavir/ritonavir high dose
arm group type: Experimental
intervention type: Drug
intervention name: Tipranavir low dose
arm group label: tipranavir/ritonavir low dose
intervention type: Drug
intervention name: Tipranavir high dose
arm group label: tipranavir/ritonavir high dose
intervention type: Drug
intervention name: Ritonavir low dose
arm group label: tipranavir/ritonavir low dose
intervention type: Drug
intervention name: Ritonavir high dose
arm group label: tipranavir/ritonavir high dose
intervention type: Drug
intervention name: Tenofovir disoproxil fumarate
arm group label: tipranavir/ritonavir high dose
arm group label: tipranavir/ritonavir low dose
criteria: 
gender: All
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: Tenofovir
mesh term: Tipranavir