<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/NCT02251223</url>
  </required_header>
  <id_info>
    <org_study_id>1182.6</org_study_id>
    <nct_id>NCT02251223</nct_id>
  </id_info>
  <brief_title>Effects of Tipranavir/Ritonavir on the Pharmacokinetic Characteristics of Triple Drug Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1-infected Subjects</brief_title>
  <official_title>An Open Label Multinational Study of the Effects of Three Dose Pairs of Tipranavir/Ritonavir (b.i.d.) on the Pharmacokinetic Characteristics of Protocol -Defined, Baseline, Triple Drug Nucleoside and Non-nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1-infected Subjects.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Primary: Sequentially determine the effects of three dose combinations of tipranavir (TPV) /&#xD;
      ritonavir (RTV) (administered b.i.d.), TPV 1250 mg/RTV 100 mg vs. TPV 750 mg/RTV 100 mg vs.&#xD;
      TPV 250 mg/RTV 200 mg on the steady-state pharmacokinetics of zidovudine, lamivudine,&#xD;
      stavudine, didanosine, abacavir, nevirapine and efavirenz at approved doses. The three&#xD;
      treatment groups will be enrolled sequentially starting with the highest tipranavir dosage&#xD;
      group first and ending with the lowest tipranavir dosage group.&#xD;
&#xD;
      Secondary: A) To assess the effects of zidovudine, lamivudine, stavudine, didanosine,&#xD;
      abacavir, nevirapine, and efavirenz on the pharmacokinetics of tipranavir/ritonavir compared&#xD;
      to historical controls.&#xD;
&#xD;
      B) To assess the safety of three tipranavir/ritonavir combinations when used in combination&#xD;
      with protocol defined antiretrovirals.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2001</start_date>
  <primary_completion_date type="Actual">February 2002</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
  </study_design_info>
  <primary_outcome>
    <measure>Change in trough plasma concentration (Cmin,ss) for non-nucleoside reverse transcriptase inhibitor (NNRTI)</measure>
    <time_frame>baseline, up to day 23</time_frame>
    <description>stratified by substance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in area under plasma concentration-time curve over dosing interval (AUC0-τ) for nucleoside reverse transcriptase inhibitor (NRTI)</measure>
    <time_frame>baseline, up to day 22</time_frame>
    <description>stratified by substance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in area under plasma concentration-time curve from 0 to 12 hours for didanosine (ddI)</measure>
    <time_frame>baseline, up to day 22</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmin,ss</measure>
    <time_frame>up to day 23</time_frame>
    <description>stratified by substance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-τ</measure>
    <time_frame>up to day 23</time_frame>
    <description>stratified by substance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>up to day 23</time_frame>
    <description>stratified by substance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum plasma concentration (Tmax)</measure>
    <time_frame>up to day 23</time_frame>
    <description>stratified by substance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (Cl/F)</measure>
    <time_frame>up to day 23</time_frame>
    <description>stratified by substance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half life (t1/2)</measure>
    <time_frame>up to day 23</time_frame>
    <description>stratified by substance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CD4 cell count</measure>
    <time_frame>up to day 23</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in HIV-1 RNA levels</measure>
    <time_frame>up to day 23</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant findings in laboratory tests</measure>
    <time_frame>up to 25 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 25 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">208</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>TPV/r low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/r medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/r high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir low dose</intervention_name>
    <arm_group_label>TPV/r low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir medium dose</intervention_name>
    <arm_group_label>TPV/r medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir high dose</intervention_name>
    <arm_group_label>TPV/r high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir low dose</intervention_name>
    <arm_group_label>TPV/r high dose</arm_group_label>
    <arm_group_label>TPV/r medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir high dose</intervention_name>
    <arm_group_label>TPV/r low dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent prior to trial participation&#xD;
&#xD;
          2. Between 18 and 75 years of age inclusive&#xD;
&#xD;
          3. Female subjects of child bearing potential are required to use a barrier contraceptive&#xD;
             method for at least 12 weeks prior to administration of study medication, during study&#xD;
             medication administration, and for 28 days after the end of the study&#xD;
&#xD;
          4. Ability to swallow capsules without difficulty&#xD;
&#xD;
          5. A Body Mass Index (BMI) between 11 and 50 kg/m2&#xD;
&#xD;
          6. Reasonable probability for completion of the study&#xD;
&#xD;
          7. Acceptable screening laboratory values. All laboratory values ≤ Grade I (e.g.,&#xD;
             creatine phosphokinase (CPK), amylase, triglycerides) are permissible if documentation&#xD;
             of stability for 2 months or more is available. Abnormalities &gt; Grade I are subject to&#xD;
             approval by BI clinical monitor or designee&#xD;
&#xD;
          8. Acceptable medical history, physical examination, ECG, and chest X-ray prior to&#xD;
             entering the treatment phase of the study&#xD;
&#xD;
          9. Willingness to abstain from alcohol from Day -2 to Day 23&#xD;
&#xD;
         10. Willingness to abstain from ingesting grapefruit, grapefruit juice, Seville oranges or&#xD;
             orange marmalade from Day -2 to Day 23&#xD;
&#xD;
         11. Negative urine drug screen for drugs of abuse. Subjects on methadone or equivalent&#xD;
             narcotic maintenance programs will be permitted to enter the study&#xD;
&#xD;
         12. Documented HIV-1 RNA load (by PCR) at screening of ≤20,000 copies/mL for at least&#xD;
             twelve weeks. Acceptable documentation would include laboratory data, a letter or a&#xD;
             verbal report from another provider noted in the subject records.&#xD;
&#xD;
         13. Stable doses of approved NRTIs and NNRTIs 2 for a minimum of twelve weeks prior to&#xD;
             study Day 0. Subjects on efavirenz must be able to tolerate daily morning (8:00 a.m.)&#xD;
             dosing starting at screening period and for 22 days of the study. Subjects receiving&#xD;
             bid ddI must be willing to accept a change to the once a day delayed release (EC)&#xD;
             formulation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female subjects who:&#xD;
&#xD;
               -  have a positive serum pregnancy test at Screening Period Day -14 to -7&#xD;
&#xD;
               -  are breast feeding&#xD;
&#xD;
          2. Receipt of any other investigational medicine for 30 days prior to Day 0&#xD;
&#xD;
          3. Receipt of any known cytochrome P450 3A4 (CYP3A4) altering drug i.e. phenothiazines,&#xD;
             cimetidine, barbiturates, ketoconazole, fluconazole, rifampin, steroids and herbal&#xD;
             medications for 30 days prior to Day 0. No antibiotics permitted within 10 days prior&#xD;
             to 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 prior to 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 or&#xD;
             gastrointestinal intolerance, or allergy that, in the opinion of the investigator,&#xD;
             might confound the results of the study or pose additional risk in administering&#xD;
             TPV/RTV&#xD;
&#xD;
          8. Any acute illness within 2 weeks prior to Day 0&#xD;
&#xD;
          9. Subjects who are currently taking any over-the-counter drug within 7 days prior to Day&#xD;
             0, or who are currently taking any prescription drug that, in the opinion of the&#xD;
             investigator (in consultation with the BI medical monitor and/or pharmacokineticist),&#xD;
             might interfere with either the absorption, distribution or metabolism of the TPV/RTV&#xD;
&#xD;
         10. Hypersensitivity to TPV, RTV or sulfonamide containing drugs&#xD;
&#xD;
         11. Using the adherence diary, subject has less than 100% documented adherence for the&#xD;
             last 14 doses (7 days) of baseline antiretroviral medications prior to Day 0. Subjects&#xD;
             has less than 100% adherence for the last 7 doses (7 days) of efavirenz and ddI&#xD;
             (delayed release) prior to Day 0&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</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>
  <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/NCT02251223
org study id: 1182.6
nct id: NCT02251223
lead sponsor: 
Primary: Sequentially determine the effects of three dose combinations of tipranavir (TPV) /
      ritonavir (RTV) (administered b.i.d.), TPV 1250 mg/RTV 100 mg vs. TPV 750 mg/RTV 100 mg vs.
      TPV 250 mg/RTV 200 mg on the steady-state pharmacokinetics of zidovudine, lamivudine,
      stavudine, didanosine, abacavir, nevirapine and efavirenz at approved doses. The three
      treatment groups will be enrolled sequentially starting with the highest tipranavir dosage
      group first and ending with the lowest tipranavir dosage group.

      Secondary: A) To assess the effects of zidovudine, lamivudine, stavudine, didanosine,
      abacavir, nevirapine, and efavirenz on the pharmacokinetics of tipranavir/ritonavir compared
      to historical controls.

      B) To assess the safety of three tipranavir/ritonavir combinations when used in combination
      with protocol defined antiretrovirals.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
measure: Change in trough plasma concentration (Cmin,ss) for non-nucleoside reverse transcriptase inhibitor (NNRTI)
time frame: baseline, up to day 23
description: stratified by substance
measure: Change in area under plasma concentration-time curve over dosing interval (AUC0-τ) for nucleoside reverse transcriptase inhibitor (NRTI)
time frame: baseline, up to day 22
description: stratified by substance
measure: Change in area under plasma concentration-time curve from 0 to 12 hours for didanosine (ddI)
time frame: baseline, up to day 22
measure: Cmin,ss
time frame: up to day 23
description: stratified by substance
measure: AUC0-τ
time frame: up to day 23
description: stratified by substance
measure: Maximum plasma concentration (Cmax)
time frame: up to day 23
description: stratified by substance
measure: Time of maximum plasma concentration (Tmax)
time frame: up to day 23
description: stratified by substance
measure: Oral clearance (Cl/F)
time frame: up to day 23
description: stratified by substance
measure: Apparent terminal half life (t1/2)
time frame: up to day 23
description: stratified by substance
measure: Change in CD4 cell count
time frame: up to day 23
measure: Change in HIV-1 RNA levels
time frame: up to day 23
measure: Number of patients with clinically significant findings in laboratory tests
time frame: up to 25 weeks
measure: Number of patients with adverse events
time frame: up to 25 weeks
arm group label: TPV/r low dose
arm group type: Experimental
arm group label: TPV/r medium dose
arm group type: Experimental
arm group label: TPV/r high dose
arm group type: Experimental
intervention type: Drug
intervention name: Tipranavir low dose
arm group label: TPV/r low dose
intervention type: Drug
intervention name: Tipranavir medium dose
arm group label: TPV/r medium dose
intervention type: Drug
intervention name: Tipranavir high dose
arm group label: TPV/r high dose
intervention type: Drug
intervention name: Ritonavir low dose
arm group label: TPV/r high dose
arm group label: TPV/r medium dose
intervention type: Drug
intervention name: Ritonavir high dose
arm group label: TPV/r low dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 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