<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/NCT02238314</url>
  </required_header>
  <id_info>
    <org_study_id>1182.2</org_study_id>
    <nct_id>NCT02238314</nct_id>
  </id_info>
  <brief_title>Exploratory Study of Tipranavir and Ritonavir in Multiple Protease Inhibitor-experienced HIV Patients</brief_title>
  <official_title>Tipranavir Disodium: An Open-Label ExploratorySstudy of Tipranavir and Ritonavir in Combination With One Nucleoside Reverse Transcriptase Inhibitor and One Non-Nucleoside Reverse Transcriptase Inhibitor in Multiple Protease Inhibitor-Experienced HIV Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The primary objective was to evaluate the antiviral activity and safety of two regimens of&#xD;
      tipranavir (500 mg BID or 1000 mg BID) plus ritonavir (100 mg BID) administered in&#xD;
      combination with 1 new nucleoside reverse transcriptase inhibitor (NRTI) + efavirenz in&#xD;
      multiple protease-inhibitor-experienced HIV-1 positive patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 1999</start_date>
  <primary_completion_date type="Actual">August 2001</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in HIV-1 RNA concentrations</measure>
    <time_frame>weeks 16, 24, 48 and 80</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ) (400 copies/mL)</measure>
    <time_frame>up to 112 weeks</time_frame>
    <description>measured by the Roche Amplicor HIV-1 Monitor™ polymerase chain reaction (PCR) Method</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of HIV-1 RNA levels BLQ (50 copies/mL)</measure>
    <time_frame>up to 112 weeks</time_frame>
    <description>measured by the Roche Amplicor UltraSensitive™ PCR Method</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with treatment-emergent and drug-related adverse events (AEs)</measure>
    <time_frame>up to 115 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with serious adverse events (SAEs)</measure>
    <time_frame>up to 115 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with grade 3 and 4 laboratory abnormalities</measure>
    <time_frame>up to 115 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in cluster of differentiation (CD) 4+ cell count responses</measure>
    <time_frame>weeks 24, 48 and 80</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in CD8+ cell count responses</measure>
    <time_frame>weeks 24, 48 and 80</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to new or recurring AIDS-defining illness</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to new or recurring HIV-related illness</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to death</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of AIDS-defining illness,</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of HIV-related illness,</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of death</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to virologic failure</measure>
    <time_frame>up to 115 weeks</time_frame>
    <description>defined as plasma HIV-1 RNA values &gt;400 copies/mL or a 0.5 log reduction from baseline at two consecutive time points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in cholesterol</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in HDL</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in triglycerides</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in blood glucose</measure>
    <time_frame>up to 115 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steady-state plasma concentrations</measure>
    <time_frame>up to week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fold-change in concentration required to produce 50% of inhibition (IC 50)</measure>
    <time_frame>Baseline, weeks 24, 48 and 80</time_frame>
    <description>sequence-based HIV-1 analysis (genotyping) and drugs susceptibility assays (phenotyping)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Tipranavir low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Tipranavir 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>Tipranavir low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir high dose</intervention_name>
    <arm_group_label>Tipranavir high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>Tipranavir high dose</arm_group_label>
    <arm_group_label>Tipranavir low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nucleoside Reverse Transcriptase Inhibitor (NRTI)</intervention_name>
    <arm_group_label>Tipranavir high dose</arm_group_label>
    <arm_group_label>Tipranavir low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)</intervention_name>
    <arm_group_label>Tipranavir high dose</arm_group_label>
    <arm_group_label>Tipranavir low dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Multiple (two or more) PI-experience. Eligible patients must have had exposure to at&#xD;
             least two antiretroviral regimens containing a single protease inhibitor or a regimen&#xD;
             containing dual protease inhibitors&#xD;
&#xD;
          -  In the investigator's opinion, the patient had adhered to PI-containing regimens&#xD;
&#xD;
          -  Exposure of ≥ 3 months to the current PI therapy&#xD;
&#xD;
          -  Exposure of ≥ 4 months to the prior PI therapy with single PI-containing regimens&#xD;
&#xD;
          -  Stable PI-containing regimen for at least 2 months prior to study entry&#xD;
&#xD;
          -  HIV-1-RNA ≥ 5,000 copies/mL&#xD;
&#xD;
          -  Cluster of differentiation (CD)4+ cell count ≥ 50 cells/mm**3&#xD;
&#xD;
          -  At least one new NRTI option available&#xD;
&#xD;
          -  Age ≥ 13 years&#xD;
&#xD;
          -  Acceptable screening laboratory values that indicated adequate baseline organ function&#xD;
             at the time of screening. Laboratory values were considered acceptable if the severity&#xD;
             was ≤ Grade 1 (AIDS Clinical Trial Group (ACTG) Grading Scale). Stable Grade 2&#xD;
             abnormalities were permitted if the values had been demonstrated and documented for at&#xD;
             least ≥ 2 months.&#xD;
&#xD;
          -  Acceptable medical history, physical examination, electrocardiogram, and chest X-ray&#xD;
             prior to entry into the treatment phase of the study&#xD;
&#xD;
          -  Agreement to use a barrier contraceptive method of birth control for at least 30 days&#xD;
             prior to study drug administration, during the study, and 30 days after the end of the&#xD;
             study&#xD;
&#xD;
          -  Ability to swallow numerous tablets and capsules without difficulty&#xD;
&#xD;
          -  Ability to understand and provide informed consent. Minors were required to have&#xD;
             approval of a parent or legal guardian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior exposure, defined as &gt; 7 treatment days, to nonnucleoside reverse transcriptase&#xD;
             inhibitor (NNRTIs) including, but not limited to: nevirapine, efavirenz, delavirdine,&#xD;
             atevirdine, MKC-442, loviride, and HBY-097&#xD;
&#xD;
          -  Clinically significant active or acute (onset within the month previous to study&#xD;
             entry) medical problems, including the following: opportunistic infections, such as&#xD;
             active cryptococcosis, Pneumocystis carinii pneumonia, herpes zoster, histoplasmosis,&#xD;
             or cytomegalovirus or nonopportunistic diseases, including, but not limited to,&#xD;
             progressive multifocal leukoencephalopathy, lymphoma, or malignancy requiring systemic&#xD;
             therapy&#xD;
&#xD;
          -  Prior exposure (&gt; 7 days) to tipranavir&#xD;
&#xD;
          -  History of clinically significant nervous system or muscle diseases, seizure disorder,&#xD;
             or psychiatric disorder that might impair adherence to the protocol&#xD;
&#xD;
          -  Taking of any known P450 3A enzyme-inducing drugs within 30 days of study entry and&#xD;
             including the following: rifabutin, rifampin, carbamazepine, dexamethasone,&#xD;
             phenobarbital, phenytoin, sulfadimidine, sulfinpyrazone, or troleandomycin&#xD;
&#xD;
          -  Hypersensitivity to tipranavir and/or ritonavir&#xD;
&#xD;
          -  Use of interferons, interleukins, HIV vaccines, or any active immunizations within 30&#xD;
             days prior to study entry&#xD;
&#xD;
          -  Taking of any investigational medication with the exception of adefovir dipivoxil&#xD;
             (Preveon™) and amprenavir (Agenerase™) within 30 days of study entry&#xD;
&#xD;
          -  Pregnancy or lactation (serum β-human chorionic gonadotrophin test had to have been&#xD;
             negative within 14 days of study entry)&#xD;
&#xD;
          -  Evidence of active substance abuse, which in the investigator's opinion, could affect&#xD;
             compliance to the protocol&#xD;
&#xD;
          -  In the investigator's judgment, inability to comply with the protocol requirements for&#xD;
             reasons other than those specified&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>N/A</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 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>September 11, 2014</last_update_submitted>
  <last_update_submitted_qc>September 11, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 12, 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>
    <mesh_term>Reverse Transcriptase Inhibitors</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/NCT02238314
org study id: 1182.2
nct id: NCT02238314
lead sponsor: 
The primary objective was to evaluate the antiviral activity and safety of two regimens of
      tipranavir (500 mg BID or 1000 mg BID) plus ritonavir (100 mg BID) administered in
      combination with 1 new nucleoside reverse transcriptase inhibitor (NRTI) + efavirenz in
      multiple protease-inhibitor-experienced HIV-1 positive patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in HIV-1 RNA concentrations
time frame: weeks 16, 24, 48 and 80
measure: Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ) (400 copies/mL)
time frame: up to 112 weeks
description: measured by the Roche Amplicor HIV-1 Monitor™ polymerase chain reaction (PCR) Method
measure: Occurrence of HIV-1 RNA levels BLQ (50 copies/mL)
time frame: up to 112 weeks
description: measured by the Roche Amplicor UltraSensitive™ PCR Method
measure: Number of patients with treatment-emergent and drug-related adverse events (AEs)
time frame: up to 115 weeks
measure: Number of patients with serious adverse events (SAEs)
time frame: up to 115 weeks
measure: Number of patients with grade 3 and 4 laboratory abnormalities
time frame: up to 115 weeks
measure: Change from baseline in cluster of differentiation (CD) 4+ cell count responses
time frame: weeks 24, 48 and 80
measure: Change from baseline in CD8+ cell count responses
time frame: weeks 24, 48 and 80
measure: Time to new or recurring AIDS-defining illness
time frame: up to 115 weeks
measure: Time to new or recurring HIV-related illness
time frame: up to 115 weeks
measure: Time to death
time frame: up to 115 weeks
measure: Occurrence of AIDS-defining illness,
time frame: up to 115 weeks
measure: Occurrence of HIV-related illness,
time frame: up to 115 weeks
measure: Occurrence of death
time frame: up to 115 weeks
measure: Time to virologic failure
time frame: up to 115 weeks
description: defined as plasma HIV-1 RNA values >400 copies/mL or a 0.5 log reduction from baseline at two consecutive time points
measure: Change from baseline in cholesterol
time frame: up to 115 weeks
measure: Change from baseline in HDL
time frame: up to 115 weeks
measure: Change from baseline in triglycerides
time frame: up to 115 weeks
measure: Change from baseline in blood glucose
time frame: up to 115 weeks
measure: Steady-state plasma concentrations
time frame: up to week 24
measure: Fold-change in concentration required to produce 50% of inhibition (IC 50)
time frame: Baseline, weeks 24, 48 and 80
description: sequence-based HIV-1 analysis (genotyping) and drugs susceptibility assays (phenotyping)
arm group label: Tipranavir low dose
arm group type: Experimental
arm group label: Tipranavir high dose
arm group type: Experimental
intervention type: Drug
intervention name: Tipranavir low dose
arm group label: Tipranavir low dose
intervention type: Drug
intervention name: Tipranavir high dose
arm group label: Tipranavir high dose
intervention type: Drug
intervention name: Ritonavir
arm group label: Tipranavir high dose
arm group label: Tipranavir low dose
intervention type: Drug
intervention name: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
arm group label: Tipranavir high dose
arm group label: Tipranavir low dose
intervention type: Drug
intervention name: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
arm group label: Tipranavir high dose
arm group label: Tipranavir low dose
criteria: 
gender: All
minimum age: 13 Years
maximum age: N/A
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
mesh term: Reverse Transcriptase Inhibitors