<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/NCT02253836</url>
  </required_header>
  <id_info>
    <org_study_id>1182.61</org_study_id>
    <nct_id>NCT02253836</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study in Healthy Adult Volunteers to Assess the Interactions Between Steady-State Tipranavir and Atazanavir in the Presence of Ritonavir</brief_title>
  <official_title>A Single-Centre Open-Label Study in Healthy Adult Volunteers to Assess the Pharmacokinetic Interactions Between Steady-State TPV (500 mg) and Single-Dose and Steady-State Atazanavir (300 mg QD) in the Presence of Ritonavir (100 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 investigate the effects of steady-state TPV/r (500 mg/100 mg BID) on the single-dose&#xD;
      and steady-state pharmacokinetics of Atazanavir (300 mg QD) co-administered with Ritonavir&#xD;
      (100 mg). To investigate the effects of single-dose and steady-state Atazanavir (300 mg) on&#xD;
      the steady-state pharmacokinetics of Tipranavir and Ritonavir.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2005</start_date>
  <primary_completion_date type="Actual">July 2005</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</measure>
    <time_frame>up to day 33</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration in plasma at 12 hr after administration for Tipranavir (TPV) and Ritonavir (RTV)</measure>
    <time_frame>12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration in plasma at 24 hr after administration for Atazanavir (TAZ)</measure>
    <time_frame>24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under plasma concentration time curve from 0-12 hours (AUC0-12h) for TPV and RTV</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-24h for TAZ</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to the maximum concentration</measure>
    <time_frame>up to day 33</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life</measure>
    <time_frame>up to day 33</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral clearance</measure>
    <time_frame>up to day 33</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution</measure>
    <time_frame>up to day 33</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to day 33</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TAZ/RTV - TPV/RTV - TPV/RTV+TAZ</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Days 1-9: single dose TAZ/RTV&#xD;
Days 16-23: morning and evening dose TPV/RTV&#xD;
Days 24-32: TPV/RTV + TAZ</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <description>TPV</description>
    <arm_group_label>TAZ/RTV - TPV/RTV - TPV/RTV+TAZ</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <description>RTV</description>
    <arm_group_label>TAZ/RTV - TPV/RTV - TPV/RTV+TAZ</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atazanavir</intervention_name>
    <description>TAZ</description>
    <arm_group_label>TAZ/RTV - TPV/RTV - TPV/RTV+TAZ</arm_group_label>
  </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 at&#xD;
             screening visit:&#xD;
&#xD;
               -  Laboratory values are considered to be acceptable if the severity of any&#xD;
                  parameter is ≤ Grade 1, based on the Division of AIDS/AIDS Clinical Trials Group&#xD;
                  Grading Scale&#xD;
&#xD;
               -  All abnormal laboratory values &gt; Grade 1 are subject to approval by the trial&#xD;
                  clinical monitor&#xD;
&#xD;
          6. Acceptable medical history, physical examination, and 12-lead ECG at screening&#xD;
&#xD;
          7. Willingness to abstain from the following starting 2 weeks prior to administration of&#xD;
             any study medication and up until the end of the study:&#xD;
&#xD;
             - Grapefruit or grapefruit juice, Red wine, Seville oranges, St. John's Wort, and Milk&#xD;
             Thistle&#xD;
&#xD;
          8. Willingness to abstain from alcohol starting 3 days prior to administration of any&#xD;
             study medication up to the end of the study&#xD;
&#xD;
          9. Willingness to abstain from the following starting 3 days prior to pharmacokinetic&#xD;
             (PK) sampling:&#xD;
&#xD;
             - Garlic supplements and Methylxanthine containing foods or drinks (including coffee,&#xD;
             tea, cola, energy drinks, chocolate, etc.)&#xD;
&#xD;
         10. Willingness to abstain from over-the-counter herbal medications for the duration of&#xD;
             the study&#xD;
&#xD;
         11. Must be a non-smoker&#xD;
&#xD;
         12. Willingness to abstain from vigorous physical exercise during intensive PK Days 1, 9,&#xD;
             23, 24 and 32&#xD;
&#xD;
         13. Reasonable probability for completion of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female subjects of reproductive potential who:&#xD;
&#xD;
               -  Have positive serum pregnancy test&#xD;
&#xD;
               -  Have not been using a barrier method of contraception for at least 3 months prior&#xD;
                  to participation in the study&#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;
                  and 60 days after completion/termination of the trial&#xD;
&#xD;
               -  Are breast-feeding&#xD;
&#xD;
          2. Participation in another trial with an investigational medicine within 2 months prior&#xD;
             to Day 0 of this study&#xD;
&#xD;
          3. Use of any medication listed in the protocol within 30 days prior to Day 0 of this&#xD;
             study&#xD;
&#xD;
          4. Use of any pharmacological contraceptive (including oral, patch or injectable&#xD;
             contraceptives) within 1 month prior to Day 0 and for the duration of the study. Due&#xD;
             to long half-life,subjects using of Depo-Provera within six months prior to Day 0 will&#xD;
             be excluded from participation in this study&#xD;
&#xD;
          5. Use of hormone replacement therapy within 1 month prior to Day 0 and anytime during&#xD;
             the study&#xD;
&#xD;
          6. Administration of antibiotics within 15 days prior to Day 0 and anytime during the&#xD;
             study&#xD;
&#xD;
          7. History of acute illness within 60 days prior to Day 0&#xD;
&#xD;
             o Subjects will be excluded for acute illnesses that occurred more than 60 days prior&#xD;
             to Day 0 if, in the opinion of the investigator, the subject does not qualify as a&#xD;
             healthy volunteer&#xD;
&#xD;
          8. Have serological evidence of hepatitis B or C virus&#xD;
&#xD;
          9. Have serological evidence of exposure to HIV&#xD;
&#xD;
         10. Alcohol or substance abuse within 1 year prior to screening or during the study&#xD;
&#xD;
         11. Blood or plasma donations within 30 days prior to Day 0 or during the study&#xD;
&#xD;
         12. 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, Ritonavir or Atazanavir to the subject&#xD;
&#xD;
         13. Subjects with pre-existing heart conduction abnormalities&#xD;
&#xD;
         14. Subjects who have taken (within 7 days prior to Day 0) any over-the-counter or&#xD;
             prescription medication that, in the opinion of the investigator in consultation with&#xD;
             the clinical monitor, might interfere with absorption, distribution, or metabolism of&#xD;
             the study medications&#xD;
&#xD;
         15. Known hypersensitivity to sulphonamide class of drugs&#xD;
&#xD;
         16. Inability to adhere to the protocol&#xD;
&#xD;
         17. Cautions or warnings in the Ritonavir and Atazanavir package insert which, in the&#xD;
             opinion of the investigator, constitute grounds for subject exclusion&#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 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>September 30, 2014</last_update_submitted>
  <last_update_submitted_qc>September 30, 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>Atazanavir Sulfate</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/NCT02253836
org study id: 1182.61
nct id: NCT02253836
lead sponsor: 
Study to investigate the effects of steady-state TPV/r (500 mg/100 mg BID) on the single-dose
      and steady-state pharmacokinetics of Atazanavir (300 mg QD) co-administered with Ritonavir
      (100 mg). To investigate the effects of single-dose and steady-state Atazanavir (300 mg) on
      the steady-state pharmacokinetics of Tipranavir and Ritonavir.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum plasma concentration
time frame: up to day 33
measure: Drug concentration in plasma at 12 hr after administration for Tipranavir (TPV) and Ritonavir (RTV)
time frame: 12 hours after drug administration
measure: Drug concentration in plasma at 24 hr after administration for Atazanavir (TAZ)
time frame: 24 hours after drug administration
measure: Area under plasma concentration time curve from 0-12 hours (AUC0-12h) for TPV and RTV
time frame: up to 12 hours after drug administration
measure: AUC0-24h for TAZ
time frame: up to 24 hours after drug administration
measure: Time from dosing to the maximum concentration
time frame: up to day 33
measure: Elimination half-life
time frame: up to day 33
measure: Oral clearance
time frame: up to day 33
measure: Volume of distribution
time frame: up to day 33
measure: Number of patients with adverse events
time frame: up to day 33
arm group label: TAZ/RTV - TPV/RTV - TPV/RTV+TAZ
arm group type: Experimental
description: Days 1-9: single dose TAZ/RTV
Days 16-23: morning and evening dose TPV/RTV
Days 24-32: TPV/RTV + TAZ
intervention type: Drug
intervention name: Tipranavir
description: TPV
arm group label: TAZ/RTV - TPV/RTV - TPV/RTV+TAZ
intervention type: Drug
intervention name: Ritonavir
description: RTV
arm group label: TAZ/RTV - TPV/RTV - TPV/RTV+TAZ
intervention type: Drug
intervention name: Atazanavir
description: TAZ
arm group label: TAZ/RTV - TPV/RTV - TPV/RTV+TAZ
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: Atazanavir Sulfate
mesh term: Tipranavir