<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/NCT02239835</url>
  </required_header>
  <id_info>
    <org_study_id>1182.4</org_study_id>
    <nct_id>NCT02239835</nct_id>
  </id_info>
  <brief_title>Tipranavir and Ritonavir vs. Saquinavir and Ritonavir Used With Two Nucleoside Reverse Transcriptase Inhibitors in Single Protease Inhibitor-experienced HIV-1 Patients</brief_title>
  <official_title>Tipranavir: An Open-label, Randomized Study Comparing Combination Therapy (Tipranavir and Ritonavir vs. Saquinavir and Ritonavir) Used With Two Nucleoside Reverse Transcriptase Inhibitors in Single Protease Inhibitor-experienced HIV-1 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>
      Objectives of the study were to evaluate the efficacy and safety of two different doses of&#xD;
      tipranavir (TPV) in combination with ritonavir (TPV/r) compared with a standard dual PI&#xD;
      combination of saquinavir (SQV) and ritonavir (RTV) and to evaluate the dose response of two&#xD;
      different doses of TPV in combination with RTV for efficacy and safety.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>December 1999</start_date>
  <primary_completion_date type="Actual">November 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 plasma HIV-1 RNA concentrations</measure>
    <time_frame>Week 16, 24 and 48</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ)</measure>
    <time_frame>up to 96 weeks</time_frame>
    <description>using the Roche Amplicor HIV Monitor™ Method [limit of detection (LD) 400 copies/mL] and the Roche Amplicor UltraSensitive Method™ (LD 50 copies/mL)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with treatment-emergent and drug-related adverse events (AEs)</measure>
    <time_frame>up to 96 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with serious adverse events (SAEs)</measure>
    <time_frame>up to 96 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with grade 3 and 4 laboratory abnormalities</measure>
    <time_frame>up to 96 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in cluster of differentiation (CD) 4+ cell count</measure>
    <time_frame>Week 16, 24 and 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to virologic failure</measure>
    <time_frame>after week 16</time_frame>
    <description>defined as plasma HIV-1 RNA values &gt;400 copies/mL at two consecutive time points 2 to 4 weeks apart</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of new or recurring AIDS-defining illnesses</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of HIV-1 related illness</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of death</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to new or recurring AIDS-defining illnesses</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to HIV-1 related illness</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to death</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in blood glucose</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in cholesterol</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in high density lipoprotein (HDL)</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in triglycerides</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to virologic response</measure>
    <time_frame>up to 96 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough plasma tipranavir concentrations</measure>
    <time_frame>up to week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sequence-based HIV-1 analysis (genotyping) and drug susceptibility assays (phenotyping)</measure>
    <time_frame>Baseline and week 24</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>TPV low dose + RTV low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV high dose + RTV low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>SQV + RTV high dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir (TPV) low dose</intervention_name>
    <arm_group_label>TPV low dose + RTV low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir (TPV) high dose</intervention_name>
    <arm_group_label>TPV high dose + RTV low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir low dose</intervention_name>
    <arm_group_label>TPV high dose + RTV low dose</arm_group_label>
    <arm_group_label>TPV low dose + RTV low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir high dose</intervention_name>
    <arm_group_label>SQV + RTV high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saquinavir</intervention_name>
    <arm_group_label>SQV + RTV high dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical failure while on the current PI-containing regimen of indinavir, nelfinavir,&#xD;
             or amprenavir&#xD;
&#xD;
          -  In the investigator's opinion, adherence to the present PI-containing regimen&#xD;
&#xD;
          -  Exposure of &gt;=6 months to the current PI therapy&#xD;
&#xD;
          -  Stable PI-containing regimen, i.e., receiving the current two reverse transcriptase&#xD;
             inhibitors (RTIs) for at least 2 months prior to study entry&#xD;
&#xD;
          -  HIV-1 RNA &gt;=1000 copies/mL (assayed using the Amplicor polymerase chain reaction (PCR)&#xD;
             method at the initial screening visit)&#xD;
&#xD;
          -  No limit in CD4+ cell count at the initial screening&#xD;
&#xD;
          -  At least two new nucleoside reverse transcriptase inhibitor (NRTI) options available&#xD;
&#xD;
          -  Age &gt;=18 years&#xD;
&#xD;
          -  Acceptable screening laboratory test values that indicated adequate baseline organ&#xD;
             function at the time of screening. Acceptable laboratory test values consisted of the&#xD;
             following: severity &lt;=Grade 1 (ACTG Grading Scale). Stable Grade 2 abnormalities were&#xD;
             permitted if the values had been demonstrated and documented for at least &gt;=2 months.&#xD;
             All laboratory values &gt;Grade 2 were subject to approval by the P&amp;U Clinical Program&#xD;
             Leader or designated personnel and subsequently by the BI designated personnel&#xD;
&#xD;
          -  Acceptable medical history, physical examination, ECG, and chest radiograph prior to&#xD;
             entry into the treatment phase of the study&#xD;
&#xD;
          -  Use of a barrier contraceptive method of birth control for at least 30 days prior to&#xD;
             study drug administration, during the study, and 30 days after study completion&#xD;
&#xD;
          -  Ability to swallow numerous tablets and capsules without difficulty&#xD;
&#xD;
          -  Ability to understand and provide informed consent. Minors had to have approval of a&#xD;
             parent or legal guardian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with more than one PI-containing regimen&#xD;
&#xD;
          -  Clinically significant active or acute (onset within the month previous to study&#xD;
             entry) medical problems, including the following: opportunistic infections, e.g.,&#xD;
             active cryptococcosis, Pneumocystis carinii pneumonia, herpes zoster, histoplasmosis,&#xD;
             or cytomegalovirus; nonopportunistic diseases, including but not limited to the&#xD;
             following: progressive multifocal leukoencephalopathy, lymphoma, or malignancy&#xD;
             requiring systemic therapy&#xD;
&#xD;
          -  Prior exposure (&gt;7 days) to tipranavir, saquinavir, or ritonavir&#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, saquinavir, or ritonavir&#xD;
&#xD;
          -  Use of interferons, interleukins, HIV vaccines, or any active immunizations within 30&#xD;
             days of study entry&#xD;
&#xD;
          -  Taking of any investigational medication with the exception of adefovir dipivoxil&#xD;
             (Preveon™) 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 substance abuse, which in the investigator's opinion could affect&#xD;
             adherence 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>18 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 15, 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 15, 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>Saquinavir</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/NCT02239835
org study id: 1182.4
nct id: NCT02239835
lead sponsor: 
Objectives of the study were to evaluate the efficacy and safety of two different doses of
      tipranavir (TPV) in combination with ritonavir (TPV/r) compared with a standard dual PI
      combination of saquinavir (SQV) and ritonavir (RTV) and to evaluate the dose response of two
      different doses of TPV in combination with RTV for efficacy and safety.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in plasma HIV-1 RNA concentrations
time frame: Week 16, 24 and 48
measure: Occurrence of HIV-1 RNA levels below the limit of quantitation (BLQ)
time frame: up to 96 weeks
description: using the Roche Amplicor HIV Monitor™ Method [limit of detection (LD) 400 copies/mL] and the Roche Amplicor UltraSensitive Method™ (LD 50 copies/mL)
measure: Number of patients with treatment-emergent and drug-related adverse events (AEs)
time frame: up to 96 weeks
measure: Number of patients with serious adverse events (SAEs)
time frame: up to 96 weeks
measure: Number of patients with grade 3 and 4 laboratory abnormalities
time frame: up to 96 weeks
measure: Change from baseline in cluster of differentiation (CD) 4+ cell count
time frame: Week 16, 24 and 48
measure: Time to virologic failure
time frame: after week 16
description: defined as plasma HIV-1 RNA values >400 copies/mL at two consecutive time points 2 to 4 weeks apart
measure: Occurrence of new or recurring AIDS-defining illnesses
time frame: up to 96 weeks
measure: Occurrence of HIV-1 related illness
time frame: up to 96 weeks
measure: Occurrence of death
time frame: up to 96 weeks
measure: Time to new or recurring AIDS-defining illnesses
time frame: up to 96 weeks
measure: Time to HIV-1 related illness
time frame: up to 96 weeks
measure: Time to death
time frame: up to 96 weeks
measure: Change from baseline in blood glucose
time frame: up to 96 weeks
measure: Change from baseline in cholesterol
time frame: up to 96 weeks
measure: Change from baseline in high density lipoprotein (HDL)
time frame: up to 96 weeks
measure: Change from baseline in triglycerides
time frame: up to 96 weeks
measure: Time to virologic response
time frame: up to 96 weeks
measure: Trough plasma tipranavir concentrations
time frame: up to week 24
measure: Sequence-based HIV-1 analysis (genotyping) and drug susceptibility assays (phenotyping)
time frame: Baseline and week 24
arm group label: TPV low dose + RTV low dose
arm group type: Experimental
arm group label: TPV high dose + RTV low dose
arm group type: Experimental
arm group label: SQV + RTV high dose
arm group type: Active Comparator
intervention type: Drug
intervention name: Tipranavir (TPV) low dose
arm group label: TPV low dose + RTV low dose
intervention type: Drug
intervention name: Tipranavir (TPV) high dose
arm group label: TPV high dose + RTV low dose
intervention type: Drug
intervention name: Ritonavir low dose
arm group label: TPV high dose + RTV low dose
arm group label: TPV low dose + RTV low dose
intervention type: Drug
intervention name: Ritonavir high dose
arm group label: SQV + RTV high dose
intervention type: Drug
intervention name: Saquinavir
arm group label: SQV + RTV high dose
criteria: 
gender: All
minimum age: 18 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: Saquinavir
mesh term: Tipranavir