<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/NCT02229760</url>
  </required_header>
  <id_info>
    <org_study_id>1182.109</org_study_id>
    <nct_id>NCT02229760</nct_id>
  </id_info>
  <brief_title>Effect of Steady State TPV/r on Intracellular Concentrations of Zidovudine and Carbovir for Patients With HIV</brief_title>
  <official_title>Effect of Steady State TPV/r 500 mg/200 mg on Intracellular Concentrations of Zidovudine Triphosphate and Carbovir Triphosphate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To determine the effect of steady-state tipranavir 500 mg/ritonavir 200 mg (TPV/r) on&#xD;
      intracellular concentrations of zidovudine triphosphate (ZDV-TP) and carbovir triphosphate&#xD;
      (CBV-TP) and plasma viral load&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>August 2006</start_date>
  <primary_completion_date type="Actual">September 2007</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-12h (Area under curve) of intracellular ZDV-TP</measure>
    <time_frame>Up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-12h (Area under curve) of carbovir-TP</measure>
    <time_frame>Up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinical significant findings in vital sings</measure>
    <time_frame>Up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinical significant findings in physical examinations</measure>
    <time_frame>Up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinical significant findings in laboratory measurements</measure>
    <time_frame>Up to 14 days after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Zidovudine (ZDV) in plasma</measure>
    <time_frame>Up to 14 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Abacavir (ABC) in plasma</measure>
    <time_frame>Up to 14 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Tipranavir (TPV) in plasma</measure>
    <time_frame>Up to 14 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of ritonavir in plasma</measure>
    <time_frame>Up to 14 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (Maximum observed concentration)</measure>
    <time_frame>Up to 14 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cp12h (Trough plasma concentration)</measure>
    <time_frame>Up to 14 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-12h (Area under curve)</measure>
    <time_frame>Up to 14 days after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 14 days after last drug adminnistration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with viral load (VL) &lt;50</measure>
    <time_frame>Up to 14 days after last drug adminnistration</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>TPV/r (Tipranavir co-administered with low dose ritonavir)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir capsules</intervention_name>
    <arm_group_label>TPV/r (Tipranavir co-administered with low dose ritonavir)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir capsules</intervention_name>
    <arm_group_label>TPV/r (Tipranavir co-administered with low dose ritonavir)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent before study participation&#xD;
&#xD;
          2. Age &gt;18 and &lt;60 years&#xD;
&#xD;
          3. Female patients of child-bearing potential who use a barrier contraceptive method for&#xD;
             at least 12 weeks before administration of study medication, during the study and for&#xD;
             28 days after administration of study medication has ended and who have a negative&#xD;
             pregnancy test result&#xD;
&#xD;
          4. Ability to swallow capsules without difficulty&#xD;
&#xD;
          5. A Body Mass Index (BMI) between 18 and 29 kg/m2&#xD;
&#xD;
          6. Reasonable probability of completing the study&#xD;
&#xD;
          7. A medical history, physical examination, and electrocardiogram (ECG) before entering&#xD;
             the study&#xD;
&#xD;
          8. Agreement to abstain from alcohol from Day -2 to Day 24&#xD;
&#xD;
          9. Agreement to abstain from ingesting grapefruit, grapefruit juice, Seville oranges or&#xD;
             orange marmalade from Day -2 to Day 24&#xD;
&#xD;
         10. Negative urine drug screen for drugs of abuse&#xD;
&#xD;
         11. Documented HIV-1 RNA load (by PCR) at screening of &lt;50 copies/mL for at least 3 months&#xD;
             and on a stable ZDV or ABC regimen for at least 6 months. Acceptable documentation&#xD;
             included laboratory data, letter, or verbal report from another provider noted in the&#xD;
             patient's records&#xD;
&#xD;
         12. All HIV-infected patients must be TPV naïve and must not have received a PI based&#xD;
             regimen within 6 months of enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female patients who had a positive serum pregnancy test during the screening period of&#xD;
             Day -14 to Day -7 or who plan to breast-feed at time (Day 0 to 30 after TPV/r&#xD;
             administration)&#xD;
&#xD;
          2. Use of any other investigational medicine within 30 days before Day 0&#xD;
&#xD;
          3. Use of any known CYP3A4 altering drug (i.e., phenothiazines, cimetidine, barbiturates,&#xD;
             ketoconazole, fluconazole, rifampin, steroids and herbal medications) within 30 days&#xD;
             before Day 0. No antibiotics were permitted within 10 days before Day 0&#xD;
&#xD;
          4. Ingestion of grapefruit, grapefruit juice, Seville oranges, or orange marmalade within&#xD;
             2 days of study entry (Day 0)&#xD;
&#xD;
          5. Blood or plasma donations (&gt;100 mL total) for research or altruistic reasons within 30&#xD;
             days before Day 0&#xD;
&#xD;
          6. Seated systolic blood pressure either &lt;100 mm Hg or &gt;150 mm Hg; resting heart rate&#xD;
             either &lt;50 beats/minute or &gt;90 beats/minute&#xD;
&#xD;
          7. History of any illness (including malabsorption, irregular food intake,&#xD;
             gastrointestinal intolerance, or allergy) that, in the opinion of the investigator,&#xD;
             might confound the results of the study or pose additional risks in administering&#xD;
             TPV/r&#xD;
&#xD;
          8. Any acute illness within 2 weeks before Day 0&#xD;
&#xD;
          9. Patients who were currently taking any over-the-counter medication within 7 days&#xD;
             before Day 0, or who were currently taking any prescription drug that, in the opinion&#xD;
             of the investigator (in consultation with the BI medical monitor or&#xD;
             pharmacokineticist), would have interfered with either the absorption, distribution,&#xD;
             or metabolism of TPV or ritonavir&#xD;
&#xD;
         10. Hypersensitivity to TPV, ritonavir, or sulfonamide containing drugs, or antiretroviral&#xD;
             drugs (marketed or experimental use as part of clinical research studies)&#xD;
&#xD;
         11. Sulfonamide allergy, that in the opinion of the investigator, might confound the&#xD;
             results of the study or pose additional risks in administering TPV/r&#xD;
&#xD;
         12. Any laboratory value outside the normal reference range that is of clinical relevance&#xD;
             at screening, according to the judgment of the investigator (i.e., aspartate&#xD;
             aminotransferase and alanine aminotransferase levels 2.5-fold and 2.5-fold higher than&#xD;
             the upper normal limit, respectively)&#xD;
&#xD;
         13. Based on the compliance diary, the patient had less than 100% documented compliance&#xD;
             for 7-14 days of background Antiretroviral (ARV) (i.e., ZDV and ABC) medications&#xD;
             before Day -5 to 0 (visit 2)&#xD;
&#xD;
         14. Use of any protease inhibitors (i.e., fosamprenavir, amprenavir, indinavir,&#xD;
             saquinavir, lopinavir, ritonavir, atazanavir, and nelfinavir) within 6 months of&#xD;
             enrollment&#xD;
&#xD;
         15. Patients who are co-infected with active Hepatitis B and/or C as determined by&#xD;
             hepatitis serology.&#xD;
&#xD;
         16. Use of any anti-platelet medications (e.g. aspirin, dipyridamole, clopidogrel, or any&#xD;
             over the counter anti-platelet medicine).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</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>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>August 28, 2014</last_update_submitted>
  <last_update_submitted_qc>August 28, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 1, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</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/NCT02229760
org study id: 1182.109
nct id: NCT02229760
lead sponsor: 
To determine the effect of steady-state tipranavir 500 mg/ritonavir 200 mg (TPV/r) on
      intracellular concentrations of zidovudine triphosphate (ZDV-TP) and carbovir triphosphate
      (CBV-TP) and plasma viral load
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-12h (Area under curve) of intracellular ZDV-TP
time frame: Up to 12 hours after drug administration
measure: AUC0-12h (Area under curve) of carbovir-TP
time frame: Up to 12 hours after drug administration
measure: Number of patients with clinical significant findings in vital sings
time frame: Up to 14 days after last drug administration
measure: Number of patients with clinical significant findings in physical examinations
time frame: Up to 14 days after last drug administration
measure: Number of patients with clinical significant findings in laboratory measurements
time frame: Up to 14 days after last drug administration
measure: Concentration of Zidovudine (ZDV) in plasma
time frame: Up to 14 days after drug administration
measure: Concentration of Abacavir (ABC) in plasma
time frame: Up to 14 days after drug administration
measure: Concentration of Tipranavir (TPV) in plasma
time frame: Up to 14 days after drug administration
measure: Concentration of ritonavir in plasma
time frame: Up to 14 days after drug administration
measure: Cmax (Maximum observed concentration)
time frame: Up to 14 days after drug administration
measure: Cp12h (Trough plasma concentration)
time frame: Up to 14 days after drug administration
measure: AUC0-12h (Area under curve)
time frame: Up to 14 days after drug administration
measure: Number of patients with adverse events
time frame: Up to 14 days after last drug adminnistration
measure: Percentage of patients with viral load (VL) <50
time frame: Up to 14 days after last drug adminnistration
arm group label: TPV/r (Tipranavir co-administered with low dose ritonavir)
arm group type: Experimental
intervention type: Drug
intervention name: Tipranavir capsules
arm group label: TPV/r (Tipranavir co-administered with low dose ritonavir)
intervention type: Drug
intervention name: Ritonavir capsules
arm group label: TPV/r (Tipranavir co-administered with low dose ritonavir)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Ritonavir
mesh term: Tipranavir