<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/NCT02249416</url>
  </required_header>
  <id_info>
    <org_study_id>1182.37</org_study_id>
    <nct_id>NCT02249416</nct_id>
  </id_info>
  <brief_title>Comparison of the Effect of Tipranavir and Ritonavir or Tipranavir and Ritonavir on the Pharmacokinetic Characteristics of Zidovudine in Healthy Volunteers</brief_title>
  <official_title>A Single Center, Open-Label, Randomised, Parallel, Multiple Dose Comparison of the Effect 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 Zidovudine 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>
      The objective of this study was to characterize the effect of two dose combinations of&#xD;
      tipranavir/ritonavir (TPV 500 mg/RTV 100 mg and TPV 750 mg/RTV 200 mg) administered twice&#xD;
      daily on the pharmacokinetics (PK) of zidovudine (ZDV) and zidovudine-glucuronide (GZDV) as&#xD;
      well as the effects of zidovudine on the pharmacokinetics of TPV/RTV&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2001</start_date>
  <primary_completion_date type="Actual">February 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 the concentration-time curve of the analyte in plasma from zero time to 12 hours (AUC0-12)</measure>
    <time_frame>Up to 12 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>Up to 24 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration in plasma at 6 hours after drug administration (Cp6h)</measure>
    <time_frame>Up to 6 h after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration in plasma at 12 hours after drug administration (Cp12h)</measure>
    <time_frame>Up to 12 h after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration at steady state (Cmax ss)</measure>
    <time_frame>Up to 24 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough plasma concentration (Cmin)</measure>
    <time_frame>Up to 24 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time (MRT)</measure>
    <time_frame>Up to 24 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half life (t1/2)</measure>
    <time_frame>Up to 24 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum concentration (tmax)</measure>
    <time_frame>Up to 24 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (CL/F)</measure>
    <time_frame>Up to 24 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal elimination phase (Vz/F)</measure>
    <time_frame>Up to 24 h after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinically significant changes in vital signs</measure>
    <time_frame>Up to day 14 after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with abnormal findings in physical examination</measure>
    <time_frame>Up to day 14 after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with abnormal changes in clinical laboratory parameters</measure>
    <time_frame>Up to day 14 after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with Adverse Events</measure>
    <time_frame>Up to day 14 after first drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV/RTV low + ZDV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/RTV high + ZDV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir (TPV) low</intervention_name>
    <arm_group_label>TPV/RTV low + ZDV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir (RTV) low</intervention_name>
    <description>Norvir®</description>
    <arm_group_label>TPV/RTV low + ZDV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir (TPV) high</intervention_name>
    <description>Retrovir®</description>
    <arm_group_label>TPV/RTV high + ZDV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir (RTV) high</intervention_name>
    <arm_group_label>TPV/RTV high + ZDV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zidovudine</intervention_name>
    <arm_group_label>TPV/RTV high + ZDV</arm_group_label>
    <arm_group_label>TPV/RTV low + ZDV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability and willingness to give written informed consent in accordance with&#xD;
             institutional and federal guidelines and to comply with the investigational nature of&#xD;
             the study and the related requirements&#xD;
&#xD;
          -  Healthy males or females between 18 and 60 years of age inclusive&#xD;
&#xD;
          -  A Body Mass Index between 18 and 35 kg/m2&#xD;
&#xD;
          -  Ability to swallow numerous large capsules without difficulty&#xD;
&#xD;
          -  Reasonable probability for completion of the study, in the opinion of the investigator&#xD;
&#xD;
          -  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;= Grade 1 based on the ACTG DAIDS Grading Scale. All abnormal laboratory&#xD;
             values &gt; Grade 1 (e.g., CPK, amylase, triglycerides) are subject to approval by the&#xD;
             BIPI clinical monitor&#xD;
&#xD;
          -  Acceptable medical history, physical examination, ECG, and Chest X-ray are required&#xD;
             prior to entering the study&#xD;
&#xD;
          -  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;
          -  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;
          -  Willingness to abstain from ingesting Seville oranges, garlic supplements, St. John's&#xD;
             Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee, tea, cola,&#xD;
             energy drinks, chocolate, etc.) within 72 hours of PK sampling days (Day 1 (Visit 3),&#xD;
             Days 11-14 (Visits 5-8))&#xD;
&#xD;
          -  Willingness to abstain from use of tobacco products for the duration of the study&#xD;
&#xD;
          -  Urine drug screen negative for illegal non-prescription drugs&#xD;
&#xD;
          -  Negative HIV serology&#xD;
&#xD;
          -  Negative for Hepatitis B surface antigen and Hepatitis C&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  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 a barrier contraceptive method for at least 3 months prior to&#xD;
                  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;
          -  Participation in another trial with an investigational medicine for 30 days prior to&#xD;
             Day 0 (Visit 2)&#xD;
&#xD;
          -  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)&#xD;
&#xD;
          -  Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within 15 days prior&#xD;
             to Day 0 (Visit 2)&#xD;
&#xD;
          -  Ingestion of Seville oranges, 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 PK sampling days [Day 1 (Visit 3), Days 11-14 (Visits 5-8)]&#xD;
&#xD;
          -  Ingestion of antibiotics within 10 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          -  Inability to comply with investigator's instructions&#xD;
&#xD;
          -  History of gastrointestinal, hepatic, or renal disorders within 60 days&#xD;
&#xD;
          -  History of alcohol abuse&#xD;
&#xD;
          -  Current use of cigarettes defined as greater than 10 cigarettes per day&#xD;
&#xD;
          -  Blood or plasma donations within 30 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          -  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;90 beats/min&#xD;
&#xD;
          -  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 zidovudine to the subject&#xD;
&#xD;
          -  Subjects who have had an acute illness within 2 weeks prior to Day 0 (Visit 2)&#xD;
&#xD;
          -  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 BIPI clinical monitor and&#xD;
             pharmacokineticist, might interfere with either the absorption, distribution or&#xD;
             metabolism of the test substances&#xD;
&#xD;
          -  Hypersensitivity to tipranavir, ritonavir, or zidovudine&#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 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>September 23, 2014</last_update_submitted>
  <last_update_submitted_qc>September 23, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 25, 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>Zidovudine</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/NCT02249416
org study id: 1182.37
nct id: NCT02249416
lead sponsor: 
The objective of this study was to characterize the effect of two dose combinations of
      tipranavir/ritonavir (TPV 500 mg/RTV 100 mg and TPV 750 mg/RTV 200 mg) administered twice
      daily on the pharmacokinetics (PK) of zidovudine (ZDV) and zidovudine-glucuronide (GZDV) as
      well as the effects of zidovudine on the pharmacokinetics of TPV/RTV
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the concentration-time curve of the analyte in plasma from zero time to 12 hours (AUC0-12)
time frame: Up to 12 h after drug administration
measure: Maximum plasma concentration (Cmax)
time frame: Up to 24 h after drug administration
measure: Drug concentration in plasma at 6 hours after drug administration (Cp6h)
time frame: Up to 6 h after drug administration
measure: Drug concentration in plasma at 12 hours after drug administration (Cp12h)
time frame: Up to 12 h after drug administration
measure: Maximum plasma concentration at steady state (Cmax ss)
time frame: Up to 24 h after drug administration
measure: Trough plasma concentration (Cmin)
time frame: Up to 24 h after drug administration
measure: Mean residence time (MRT)
time frame: Up to 24 h after drug administration
measure: Terminal half life (t1/2)
time frame: Up to 24 h after drug administration
measure: Time of maximum concentration (tmax)
time frame: Up to 24 h after drug administration
measure: Oral clearance (CL/F)
time frame: Up to 24 h after drug administration
measure: Apparent volume of distribution during the terminal elimination phase (Vz/F)
time frame: Up to 24 h after drug administration
measure: Number of participants with clinically significant changes in vital signs
time frame: Up to day 14 after first drug administration
measure: Number of participants with abnormal findings in physical examination
time frame: Up to day 14 after first drug administration
measure: Number of participants with abnormal changes in clinical laboratory parameters
time frame: Up to day 14 after first drug administration
measure: Number of participants with Adverse Events
time frame: Up to day 14 after first drug administration
arm group label: TPV/RTV low + ZDV
arm group type: Experimental
arm group label: TPV/RTV high + ZDV
arm group type: Experimental
intervention type: Drug
intervention name: Tipranavir (TPV) low
arm group label: TPV/RTV low + ZDV
intervention type: Drug
intervention name: Ritonavir (RTV) low
description: Norvir®
arm group label: TPV/RTV low + ZDV
intervention type: Drug
intervention name: Tipranavir (TPV) high
description: Retrovir®
arm group label: TPV/RTV high + ZDV
intervention type: Drug
intervention name: Ritonavir (RTV) high
arm group label: TPV/RTV high + ZDV
intervention type: Drug
intervention name: Zidovudine
arm group label: TPV/RTV high + ZDV
arm group label: TPV/RTV low + ZDV
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: Zidovudine
mesh term: Tipranavir