<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/NCT02251171</url>
  </required_header>
  <id_info>
    <org_study_id>1182.44</org_study_id>
    <nct_id>NCT02251171</nct_id>
  </id_info>
  <brief_title>Effects of Steady-state TPV/RTV on the Single-dose Pharmacokinetics of Rifabutin and the Effects of Single-dose Rifabutin on the Steady-state Pharmacokinetics of TPV in Healthy Adult Volunteers</brief_title>
  <official_title>A Single-centre Open-label Study in Healthy Adult Volunteers to Determine the Effects of Steady-state TPV/RTV (500 mg/200 mg) on the Single-dose Pharmacokinetics of Rifabutin (MYCOBUTIN®) 150 mg, and the Effects of Single-dose Rifabutin (150 mg) on the Steady-state Pharmacokinetics of TPV 500 mg (Co-administered With RTV 200 mg)</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 determine the effects of steady-state Tipranavir (TPV) / Ritonavir (RTV)&#xD;
      (500mg/200mg bid) on the single-dose pharmacokinetics of Rifabutin (RFB) and to determine the&#xD;
      effects of single-dose RFB on the steady-state pharmacokinetics of TPV 500mg (co-administered&#xD;
      with RTV 200mg)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2003</start_date>
  <primary_completion_date type="Actual">October 2003</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum plasma concentration of the analytes in plasma (Cmax)</measure>
    <time_frame>up to 144 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration of the analytes in plasma at 12 hours after administration (Cp12h)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under plasma concentration time curve from 0-12 hours (AUC0-12h)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma drug concentration-time curve from time zero to infinity of the analytes (AUC0-∞)</measure>
    <time_frame>up to 144 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (CL/F)</measure>
    <time_frame>up to 144 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum concentration (Tmax)</measure>
    <time_frame>up to 144 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution (V)</measure>
    <time_frame>up to 144 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half life (t1/2)</measure>
    <time_frame>up to 144 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 24 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 21 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV/RTV - Rifabutin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Day 1: single dose Rifabutin&#xD;
Days 8-20: morning and evening doses of Tipranavir/Ritonavir&#xD;
Day 15: single dose Rifabutin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <arm_group_label>TPV/RTV - Rifabutin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>TPV/RTV - Rifabutin</arm_group_label>
    <other_name>Norvir-SEC®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifabutin</intervention_name>
    <arm_group_label>TPV/RTV - Rifabutin</arm_group_label>
    <other_name>Mycobutin®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female subjects between 18 and 60 years of age inclusive&#xD;
&#xD;
          2. A Body Mass Index (BMI) between 18 and 29 kg/m2&#xD;
&#xD;
          3. Signed informed consent prior to trial participation&#xD;
&#xD;
          4. Ability to swallow multiple large capsules without difficulty&#xD;
&#xD;
          5. 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 was less than or equal to Grade 1, based on the AIDS Clinical Trials Group&#xD;
             (ACTG) Grading Scale. All abnormal laboratory values greater than Grade 1 are subject&#xD;
             to approval by the trial clinical monitor&#xD;
&#xD;
          6. Acceptable medical history, physical examination, and 12-lead ECG are required prior&#xD;
             to entering the treatment phase of the study. The requirement for chest X-ray is left&#xD;
             to the investigator's discretion&#xD;
&#xD;
          7. Willingness to abstain from the following starting 14 days prior to any administration&#xD;
             of study drug up until the end of the study:&#xD;
&#xD;
               -  Grapefruit or grapefruit juice&#xD;
&#xD;
               -  Red wine&#xD;
&#xD;
               -  Seville oranges&#xD;
&#xD;
               -  St. John's Wort or Milk Thistle&#xD;
&#xD;
          8. Willingness to abstain from alcohol starting 2 days prior to administration of any&#xD;
             study drug up to the end of the study&#xD;
&#xD;
          9. Willingness to abstain from the following within 72 hours of pharmacokinetic (PK)&#xD;
             sampling:&#xD;
&#xD;
               -  Garlic supplements&#xD;
&#xD;
               -  Methylxanthine containing drinks (coffee, tea, cola, energy drinks, chocolate,&#xD;
                  etc.)&#xD;
&#xD;
         10. Willingness to abstain from over the counter herbal medications for the duration of&#xD;
             the study&#xD;
&#xD;
         11. Have been non-smokers for 3 months&#xD;
&#xD;
         12. Willingness to abstain from vigorous physical exercise during intensive PK study Days&#xD;
             1, 14, and 15&#xD;
&#xD;
         13. Reasonable probability for completion of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        As a guideline, subjects who have abnormal laboratory values at screening, and who are&#xD;
        taking prescription medications are excluded:&#xD;
&#xD;
          1. Female subjects with reproductive potential who:&#xD;
&#xD;
               -  Have positive serum β-human chorionic gonadotropin at Visit 1, or on study Day 0&#xD;
                  or study Day 1&#xD;
&#xD;
               -  Have not been using a barrier contraceptive method for at least 3 months prior to&#xD;
                  Visit 3 (study Day 1)&#xD;
&#xD;
               -  Are not willing to use a reliable method of barrier contraception (such as&#xD;
                  diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during&#xD;
                  the trial and 60 days after completion/termination&#xD;
&#xD;
               -  Are breast-feeding&#xD;
&#xD;
          2. Participation in another trial with an investigational medicine within 60 days prior&#xD;
             to study Day 0 (Visit 2)&#xD;
&#xD;
          3. Use of any medication listed in Protocol within 30 days prior to study Day 0 (Visit 2)&#xD;
&#xD;
          4. Use of any pharmacological contraceptive (including oral, patch or injectable&#xD;
             contraceptives) within 1 month prior to study Day 0 and for the duration of the study.&#xD;
             Use of Depo-Provera is excluded for six months prior to study Day 0&#xD;
&#xD;
          5. Use of hormone replacement therapy within 1 month prior to study Day 0 and for the&#xD;
             duration of the study&#xD;
&#xD;
          6. Administration of antibiotics within 10 days prior to study Day 0 (Visit 2) or during&#xD;
             the trial&#xD;
&#xD;
          7. History of acute illness within sixty (60) days of study Day 0. Subjects are excluded&#xD;
             if they have an acute illness greater than sixty days prior to study Day 0 if, in the&#xD;
             opinion of the investigator, the subject did not qualify as a healthy volunteer&#xD;
&#xD;
          8. History of thrombotic disease&#xD;
&#xD;
          9. History of migraine headache&#xD;
&#xD;
         10. Have serological evidence of hepatitis B or C virus&#xD;
&#xD;
         11. Have serological evidence of exposure to HIV&#xD;
&#xD;
         12. Recent history of alcohol or substance abuse (within 1 year of screening)&#xD;
&#xD;
         13. Blood or plasma donations within 30 days prior to study Day 0 (Visit 2) or during the&#xD;
             trial&#xD;
&#xD;
         14. 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. For subjects with a resting&#xD;
             heart rate below 50, or above 90, the investigator may discuss their exclusion with&#xD;
             the clinical monitor on a case-by-case basis&#xD;
&#xD;
         15. Subjects with 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 TPV, RTV or RFB to the subject&#xD;
&#xD;
         16. Subjects who have taken (within 7 days prior to study Day 0) or are taking any&#xD;
             over-the-counter or prescription drug that, in the opinion of the investigator in&#xD;
             consultation with the clinical monitor, might interfere with either the absorption,&#xD;
             distribution or metabolism of the test substances&#xD;
&#xD;
         17. Known hypersensitivity to TPV, RTV, RFB, or sulphonamide class of drugs&#xD;
&#xD;
         18. Inability to adhere to the protocol&#xD;
&#xD;
         19. Cautions or warnings in the RTV and RFB package insert which, in the judgment of the&#xD;
             investigator, should exclude a subject&#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>Tipranavir</mesh_term>
    <mesh_term>Rifabutin</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/NCT02251171
org study id: 1182.44
nct id: NCT02251171
lead sponsor: 
Study to determine the effects of steady-state Tipranavir (TPV) / Ritonavir (RTV)
      (500mg/200mg bid) on the single-dose pharmacokinetics of Rifabutin (RFB) and to determine the
      effects of single-dose RFB on the steady-state pharmacokinetics of TPV 500mg (co-administered
      with RTV 200mg)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum plasma concentration of the analytes in plasma (Cmax)
time frame: up to 144 hours after drug administration
measure: Drug concentration of the analytes in plasma at 12 hours after administration (Cp12h)
time frame: up to 12 hours after drug administration
measure: Area under plasma concentration time curve from 0-12 hours (AUC0-12h)
time frame: up to 12 hours after drug administration
measure: Area under the plasma drug concentration-time curve from time zero to infinity of the analytes (AUC0-∞)
time frame: up to 144 hours after drug administration
measure: Oral clearance (CL/F)
time frame: up to 144 hours after drug administration
measure: Time of maximum concentration (Tmax)
time frame: up to 144 hours after drug administration
measure: Volume of distribution (V)
time frame: up to 144 hours after drug administration
measure: Apparent terminal half life (t1/2)
time frame: up to 144 hours after drug administration
measure: Number of subjects with adverse events
time frame: up to 24 days
measure: Number of subjects with abnormal changes in laboratory parameters
time frame: up to 21 days
arm group label: TPV/RTV - Rifabutin
arm group type: Experimental
description: Day 1: single dose Rifabutin
Days 8-20: morning and evening doses of Tipranavir/Ritonavir
Day 15: single dose Rifabutin
intervention type: Drug
intervention name: Tipranavir
arm group label: TPV/RTV - Rifabutin
intervention type: Drug
intervention name: Ritonavir
arm group label: TPV/RTV - Rifabutin
other name: Norvir-SEC®
intervention type: Drug
intervention name: Rifabutin
arm group label: TPV/RTV - Rifabutin
other name: Mycobutin®
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: Tipranavir
mesh term: Rifabutin