<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/NCT02226991</url>
  </required_header>
  <id_info>
    <org_study_id>1182.102</org_study_id>
    <nct_id>NCT02226991</nct_id>
  </id_info>
  <brief_title>Effects of Steady-state Efavirenz 600 mg QD (Sustiva®) on Tipranavir Concentration at Steady-state in Healthy Adult Volunteers</brief_title>
  <official_title>A Single-centre, Open-label Study to Assess the Effects of Steady-state Efavirenz 600 mg QD (Sustiva®) on Tipranavir Concentration When Tipranavir/Ritonavir Are Administered at Doses 500 mg/200 mg BID to Steady-state in Healthy Adult 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 investigate the effects of steady-state Efavirenz (600 mg QD) on the steady-state&#xD;
      pharmacokinetics of Tipranavir (500 mg BID) coadministered with Ritonavir (200 mg BID)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2006</start_date>
  <primary_completion_date type="Actual">July 2006</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 at steady state (Cmax)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration in plasma at 12 hours after administration (Cp12h)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
    <description>Tipranavir (TPV)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Last measured drug concentration in plasma (Cplast)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
    <description>Ritonavir (RTV)</description>
  </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>
  <secondary_outcome>
    <measure>Trough plasma concentration (Cmin)</measure>
    <time_frame>before drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to the maximum concentration (tmax)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life (t1/2)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (CL/F)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution (Vz/F)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 38 days after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in laboratory tests</measure>
    <time_frame>up to 38 days after first drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV/RTV/EFV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>tipranavir (TPV) + ritonavir (RTV) from day 1 to day 24 efavirenz (EFV) from day 10 to day 23</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <arm_group_label>TPV/RTV/EFV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>TPV/RTV/EFV</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Efavirenz</intervention_name>
    <arm_group_label>TPV/RTV/EFV</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects between 18 and 60 years of age inclusive&#xD;
&#xD;
          2. A Body Mass Index (BMI) between 18 and 29.9 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 (DAIDS)/AIDS Clinical Trials&#xD;
                  Group (ACTG) Grading Scale&#xD;
&#xD;
               -  All abnormal laboratory values &gt;Grade 1 are subject to approval by the BI 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&#xD;
                  Milk 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&#xD;
                  coffee, tea, cola, energy drinks, chocolate, etc.), apples or apple juice&#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; Days&#xD;
             10 and 24&#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. Use of any pharmacological contraceptive (including oral, patch or injectable&#xD;
             contraceptives) within 1 month prior to Day 1 and for the duration of the study.&#xD;
&#xD;
             Due to long half-life, subjects using Depo-Provera® within six months prior to Day 1&#xD;
             will be excluded from participation in this study&#xD;
&#xD;
          3. Use of hormone replacement therapy within 1 month prior to Day 1 and anytime during&#xD;
             the study&#xD;
&#xD;
          4. Participation in another trial with an investigational medicine within 2 months prior&#xD;
             to Day 1 of this study&#xD;
&#xD;
          5. Use of any medication listed in Appendix 10.5 within 30 days prior to Day 1 of this&#xD;
             study&#xD;
&#xD;
          6. Administration of antibiotics within 15 days prior to Day 1 and anytime during the&#xD;
             study&#xD;
&#xD;
          7. History of acute illness within 60 days prior to Day 1&#xD;
&#xD;
               -  Subjects will be excluded for acute illnesses that occurred more than 60 days&#xD;
                  prior to Day 1 if, in the opinion of the investigator, the subject does not&#xD;
                  qualify as a healthy volunteer&#xD;
&#xD;
          8. Have serological evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV)&#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 1 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 TPV, RTV or EFV to the subject&#xD;
&#xD;
         13. History of a psychiatric disorder that required pharmacological or other psychological&#xD;
             treatment&#xD;
&#xD;
         14. Subjects who have taken (within 7 days prior to Day 1) any over-the-counter or&#xD;
             prescription medication that, in the opinion of the investigator in consultation with&#xD;
             the sponsor's clinical monitor, might interfere with absorption, distribution, or&#xD;
             metabolism of the study medications&#xD;
&#xD;
         15. Known hypersensitivity to sulphonamide class of drugs&#xD;
&#xD;
         16. Known hypersensitivity to TPV, RTV, EFV or antiretroviral drugs (marketed or&#xD;
             experimental use as part of clinical research studies)&#xD;
&#xD;
         17. Known elevated liver enzymes in past trials with any compound&#xD;
&#xD;
         18. Inability to adhere to the protocol&#xD;
&#xD;
         19. Cautions or warnings in the RTV and EFV package insert which, in the opinion of the&#xD;
             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>August 2014</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>August 26, 2014</last_update_submitted>
  <last_update_submitted_qc>August 26, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 27, 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>Efavirenz</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/NCT02226991
org study id: 1182.102
nct id: NCT02226991
lead sponsor: 
Study to investigate the effects of steady-state Efavirenz (600 mg QD) on the steady-state
      pharmacokinetics of Tipranavir (500 mg BID) coadministered with Ritonavir (200 mg BID)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum plasma concentration at steady state (Cmax)
time frame: up to 12 hours after drug administration
measure: Drug concentration in plasma at 12 hours after administration (Cp12h)
time frame: up to 12 hours after drug administration
description: Tipranavir (TPV)
measure: Last measured drug concentration in plasma (Cplast)
time frame: up to 12 hours after drug administration
description: Ritonavir (RTV)
measure: Area under plasma concentration time curve from 0-12 hours (AUC0-12h)
time frame: up to 12 hours after drug administration
measure: Trough plasma concentration (Cmin)
time frame: before drug administration
measure: Time from dosing to the maximum concentration (tmax)
time frame: up to 12 hours after drug administration
measure: Elimination half-life (t1/2)
time frame: up to 12 hours after drug administration
measure: Oral clearance (CL/F)
time frame: up to 12 hours after drug administration
measure: Volume of distribution (Vz/F)
time frame: up to 12 hours after drug administration
measure: Number of subjects with adverse events
time frame: up to 38 days after first drug administration
measure: Number of subjects with clinically significant findings in laboratory tests
time frame: up to 38 days after first drug administration
arm group label: TPV/RTV/EFV
arm group type: Experimental
description: tipranavir (TPV) + ritonavir (RTV) from day 1 to day 24 efavirenz (EFV) from day 10 to day 23
intervention type: Drug
intervention name: Tipranavir
arm group label: TPV/RTV/EFV
intervention type: Drug
intervention name: Ritonavir
arm group label: TPV/RTV/EFV
intervention type: Drug
intervention name: Efavirenz
arm group label: TPV/RTV/EFV
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: Efavirenz