<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/NCT02251132</url>
  </required_header>
  <id_info>
    <org_study_id>1182.5</org_study_id>
    <nct_id>NCT02251132</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Tipranavir Soft Elastic Capsules (SEDDS) and Ritonavir and Their Effects on Cytochrome P-450 (3A4) in Healthy Volunteers</brief_title>
  <official_title>An Open-label, Parallel Group, Multiple-dose Investigation of the Pharmacokinetics of Tipranavir Soft Elastic Capsules SEDDS and Ritonavir Soft Gel Capsules and Their Effects on Cytochrome P-450 (3A4) Activity in Normal Healthy 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>
      The objective of this study is to establish the tipranavir-ritonavir steady-state&#xD;
      dose-exposure relationships when administered on a b.i.d. dosing regimen; to determine the&#xD;
      effects of tipranavir (TPV) and ritonavir (RTV) on cytochrome P-450 (CYP3A4) activity; to&#xD;
      establish the dependency of the TPV M1 metabolite on RTV co-administration. Additionally, the&#xD;
      short-term safety and tolerance of this drug combination will be evaluated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2000</start_date>
  <primary_completion_date type="Actual">December 2000</primary_completion_date>
  <phase>Phase 1</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>Trough plasma concentration at steady state (Cmin,ss)</measure>
    <time_frame>up to 24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration at steady state (Cmax,ss)</measure>
    <time_frame>up to 24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of maximum concentration (tmax)</measure>
    <time_frame>up to 24 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration time curve from 0 to 12 hours (AUC0-12)</measure>
    <time_frame>up to 12 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (Cl/F)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half life (t1/2)</measure>
    <time_frame>up to 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of erythromycin metabolized per hour</measure>
    <time_frame>up to 24 hours</time_frame>
    <description>Erythromycin breath test (ERMBT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant findings in laboratory tests</measure>
    <time_frame>up to 32 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 32 days</time_frame>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">113</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV/RTV Low 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/RTV Low 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/RTV Low 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/RTV Medium 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/RTV Medium 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/RTV High 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/RTV High 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/RTV High 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV low 1</intervention_name>
    <arm_group_label>TPV/RTV Low 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV low 2</intervention_name>
    <arm_group_label>TPV/RTV Low 2</arm_group_label>
    <arm_group_label>TPV/RTV Low 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV medium</intervention_name>
    <arm_group_label>TPV/RTV Medium 1</arm_group_label>
    <arm_group_label>TPV/RTV Medium 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV high 1</intervention_name>
    <arm_group_label>TPV/RTV High 1</arm_group_label>
    <arm_group_label>TPV/RTV High 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV high 2</intervention_name>
    <arm_group_label>TPV/RTV High 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RTV low</intervention_name>
    <arm_group_label>TPV/RTV High 1</arm_group_label>
    <arm_group_label>TPV/RTV Low 2</arm_group_label>
    <arm_group_label>TPV/RTV Medium 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir high</intervention_name>
    <arm_group_label>TPV/RTV High 2</arm_group_label>
    <arm_group_label>TPV/RTV High 3</arm_group_label>
    <arm_group_label>TPV/RTV Low 1</arm_group_label>
    <arm_group_label>TPV/RTV Low 3</arm_group_label>
    <arm_group_label>TPV/RTV Medium 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Radiolabelled erythromycin</intervention_name>
    <arm_group_label>TPV/RTV High 1</arm_group_label>
    <arm_group_label>TPV/RTV High 2</arm_group_label>
    <arm_group_label>TPV/RTV High 3</arm_group_label>
    <arm_group_label>TPV/RTV Low 1</arm_group_label>
    <arm_group_label>TPV/RTV Low 2</arm_group_label>
    <arm_group_label>TPV/RTV Low 3</arm_group_label>
    <arm_group_label>TPV/RTV Medium 1</arm_group_label>
    <arm_group_label>TPV/RTV Medium 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female between 18 and 75 years of age inclusive&#xD;
&#xD;
          -  Female subjects of child-bearing potential are required to use a barrier contraceptive&#xD;
             method for at least 3 months prior to administration of study medication, during study&#xD;
             medication administration and for 30 days after the end of the study&#xD;
&#xD;
          -  Ability to swallow numerous large capsules without difficulty&#xD;
&#xD;
          -  A body mass index (BMI) between 19 and 29 kg/m2&#xD;
&#xD;
          -  Signed informed consent prior to trial participation&#xD;
&#xD;
          -  Reasonable probability for completion of the study&#xD;
&#xD;
          -  Acceptable screening laboratory values that indicate adequate baseline organ function&#xD;
             are required at the time of screening. Laboratory values are considered to be&#xD;
             acceptable if severity is no higher than Grade 1 based on the AIDS Clinical Trials&#xD;
             Group (ACTG) Grading Scale. All laboratory values &gt; Grade 1 are subject to approval by&#xD;
             the BIPI clinical monitor&#xD;
&#xD;
          -  Acceptable medical history, physical examination, electrocardiogram, and chest X-ray&#xD;
             are required prior to entering the treatment phase of the study&#xD;
&#xD;
          -  Willingness to abstain from alcohol for 48 hours prior to study Day 0 and abstain from&#xD;
             alcohol for the duration of the study&#xD;
&#xD;
          -  Willingness to abstain from ingesting grapefruit or grapefruit juice for the duration&#xD;
             of the study&#xD;
&#xD;
          -  Urine drug screen negative for drugs of abuse&#xD;
&#xD;
          -  Negative HIV serology&#xD;
&#xD;
          -  Negative for Hepatitis B surface antigen and Hepatitis C antibody&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects who:&#xD;
&#xD;
               -  have a positive serum pregnancy test at Visits 1 or 2 OR&#xD;
&#xD;
               -  are breastfeeding&#xD;
&#xD;
          -  Receipt of any other investigational medicine for 30 days prior to Day 0&#xD;
&#xD;
          -  Receipt of any known enzyme altering drug for 30 days prior to Day 0, grapefruit and&#xD;
             grapefruit juice within 15 days prior to Day 0 and antibiotics within 10 days prior to&#xD;
             Day 0&#xD;
&#xD;
          -  Excessive cigarette smoking, defined as greater than 10 cigarettes per day&#xD;
&#xD;
          -  Blood or plasma donation within 30 days prior to Day 0&#xD;
&#xD;
          -  Subjects with a seated systolic blood pressure either &lt; 100 mg Hg or &gt; 150 mm Hg;&#xD;
             resting heart rate either &lt; 50 beats/min or &gt; 90 beats/min&#xD;
&#xD;
          -  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 tipranavir or ritonavir to the subject&#xD;
&#xD;
          -  Subjects who have had an acute illness within 2 weeks prior to Day 0&#xD;
&#xD;
          -  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 BIPI medical monitor and pharmacokineticist,&#xD;
             might interfere with either the absorption, distribution or metabolism of the test&#xD;
             substances&#xD;
&#xD;
          -  Hypersensitivity to tipranavir, ritonavir or sulfonamide containing drugs&#xD;
&#xD;
          -  Evidence of active substance abuse that, in the investigator's opinion, could affect&#xD;
             study adherence&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 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>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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Erythromycin</mesh_term>
    <mesh_term>Erythromycin Estolate</mesh_term>
    <mesh_term>Erythromycin Ethylsuccinate</mesh_term>
    <mesh_term>Erythromycin stearate</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/NCT02251132
org study id: 1182.5
nct id: NCT02251132
lead sponsor: 
The objective of this study is to establish the tipranavir-ritonavir steady-state
      dose-exposure relationships when administered on a b.i.d. dosing regimen; to determine the
      effects of tipranavir (TPV) and ritonavir (RTV) on cytochrome P-450 (CYP3A4) activity; to
      establish the dependency of the TPV M1 metabolite on RTV co-administration. Additionally, the
      short-term safety and tolerance of this drug combination will be evaluated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Trough plasma concentration at steady state (Cmin,ss)
time frame: up to 24 hours
measure: Maximum plasma concentration at steady state (Cmax,ss)
time frame: up to 24 hours
measure: Time of maximum concentration (tmax)
time frame: up to 24 hours
measure: Area under the plasma concentration time curve from 0 to 12 hours (AUC0-12)
time frame: up to 12 hours
measure: Oral clearance (Cl/F)
time frame: up to 24 hours
measure: Apparent terminal half life (t1/2)
time frame: up to 24 hours
measure: Percent of erythromycin metabolized per hour
time frame: up to 24 hours
description: Erythromycin breath test (ERMBT)
measure: Number of subjects with clinically significant findings in laboratory tests
time frame: up to 32 days
measure: Number of subjects with adverse events
time frame: up to 32 days
arm group label: TPV/RTV Low 1
arm group type: Experimental
arm group label: TPV/RTV Low 2
arm group type: Experimental
arm group label: TPV/RTV Low 3
arm group type: Experimental
arm group label: TPV/RTV Medium 1
arm group type: Experimental
arm group label: TPV/RTV Medium 2
arm group type: Experimental
arm group label: TPV/RTV High 1
arm group type: Experimental
arm group label: TPV/RTV High 2
arm group type: Experimental
arm group label: TPV/RTV High 3
arm group type: Experimental
intervention type: Drug
intervention name: TPV low 1
arm group label: TPV/RTV Low 1
intervention type: Drug
intervention name: TPV low 2
arm group label: TPV/RTV Low 2
arm group label: TPV/RTV Low 3
intervention type: Drug
intervention name: TPV medium
arm group label: TPV/RTV Medium 1
arm group label: TPV/RTV Medium 2
intervention type: Drug
intervention name: TPV high 1
arm group label: TPV/RTV High 1
arm group label: TPV/RTV High 2
intervention type: Drug
intervention name: TPV high 2
arm group label: TPV/RTV High 3
intervention type: Drug
intervention name: RTV low
arm group label: TPV/RTV High 1
arm group label: TPV/RTV Low 2
arm group label: TPV/RTV Medium 1
intervention type: Drug
intervention name: Ritonavir high
arm group label: TPV/RTV High 2
arm group label: TPV/RTV High 3
arm group label: TPV/RTV Low 1
arm group label: TPV/RTV Low 3
arm group label: TPV/RTV Medium 2
intervention type: Drug
intervention name: Radiolabelled erythromycin
arm group label: TPV/RTV High 1
arm group label: TPV/RTV High 2
arm group label: TPV/RTV High 3
arm group label: TPV/RTV Low 1
arm group label: TPV/RTV Low 2
arm group label: TPV/RTV Low 3
arm group label: TPV/RTV Medium 1
arm group label: TPV/RTV Medium 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Ritonavir
mesh term: Erythromycin
mesh term: Erythromycin Estolate
mesh term: Erythromycin Ethylsuccinate
mesh term: Erythromycin stearate