<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/NCT02251769</url>
  </required_header>
  <id_info>
    <org_study_id>1182.11</org_study_id>
    <nct_id>NCT02251769</nct_id>
  </id_info>
  <brief_title>Effects of Single-dose and Steady-state TPV/r on the Steady-state Pharmacokinetics of Clarithromycin and a Preliminary Assessment of the Effects of a Standard High-fat Test Meal on the Steady-state Pharmacokinetics of Tipranavir</brief_title>
  <official_title>A Single-centre Open-label Study in Healthy Adult Volunteers to Determine the Effects of Single-dose and Steady-state TPV/r (500 mg/200 mg) on the Steady-state Pharmacokinetics of Clarithromycin (BIAXIN®) 500 mg Bid and a Preliminary Assessment of the Effects of a Standard High-fat Test Meal on the Steady-state Pharmacokinetics of Tipranavir</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To determine the effects of single-dose and steady-state Tipranavir/Ritonavir (TPV/r) at 500&#xD;
      mg/200 mg bid on the steady-state pharmacokinetics of clarithromycin and to determine the&#xD;
      effects of a standard high-fat test meal on the steady-state pharmacokinetics of tipranavir.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2003</start_date>
  <primary_completion_date type="Actual">September 2003</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>Area under plasma concentration time curve from 0-12 hours (AUC0-12h)</measure>
    <time_frame>up to 12 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>up to 12 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma trough concentration (Cp12h)</measure>
    <time_frame>up to 12 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (CL/F)</measure>
    <time_frame>up to 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution (V)</measure>
    <time_frame>up to 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half life (t1/2)</measure>
    <time_frame>up to 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum concentration (Tmax)</measure>
    <time_frame>up to 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Residency Time (MRT)</measure>
    <time_frame>up to 12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant laboratory findings</measure>
    <time_frame>up to day 13</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Sequential administration</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <arm_group_label>Sequential administration</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>Sequential administration</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clarithromycin</intervention_name>
    <arm_group_label>Sequential administration</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High-Fat Test Meal</intervention_name>
    <arm_group_label>Sequential administration</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects between 18 and 60 years of age inclusive&#xD;
&#xD;
          -  A Body Mass Index (BMI) between 18 and 29 kg/m2&#xD;
&#xD;
          -  Signed informed consent prior to trial participation&#xD;
&#xD;
          -  Ability to swallow multiple capsules without difficulty&#xD;
&#xD;
          -  Ability to ingest a standard high-fat test meal&#xD;
&#xD;
          -  Acceptable laboratory values that indicated adequate baseline organ function were&#xD;
             required at the time of screening. Laboratory values were considered to be acceptable&#xD;
             if severity was less than or equal to Grade 1, based on the AIDS Clinical Trials Group&#xD;
             (ACTG) Grading Scale&#xD;
&#xD;
          -  Acceptable medical history, physical examination and 12-lead ECG were required prior&#xD;
             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. In addition, ingestion of red wine is not&#xD;
             allowed within 5 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          -  Willingness to abstain from grapefruit or grapefruit juice or products containing&#xD;
             grapefruit juice starting 10 days prior to any administration of study drug up until&#xD;
             the end of the study&#xD;
&#xD;
          -  Willingness to abstain from ingestion of Seville oranges, garlic supplements, St.&#xD;
             John's Wort, or Milk Thistle, within 5 days of treatment and for the duration of the&#xD;
             study&#xD;
&#xD;
          -  Willingness to abstain from methylxanthine-containing drinks or foods (coffee, tea,&#xD;
             cola, energy drinks, chocolate, etc.) within 48 hours of each pharmacokinetic sampling&#xD;
             day and until after the last sample from each of the intensive sampling days was&#xD;
             collected&#xD;
&#xD;
          -  Willingness to abstain from over the counter herbal medications for the duration of&#xD;
             the study&#xD;
&#xD;
          -  Willingness to abstain from vigorous physical exercise during intensive&#xD;
             pharmacokinetic days&#xD;
&#xD;
          -  Reasonable probability for completion of the study&#xD;
&#xD;
          -  Non-smokers for at least 3 months prior to Day 0&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects who are of reproductive potential and who:&#xD;
&#xD;
               1. Have positive serum β-hCG at Visit 1, or on Day 0&#xD;
&#xD;
               2. Are not using a barrier contraceptive method for at least 3 months prior to Visit&#xD;
                  2 (Day 0)&#xD;
&#xD;
               3. Are not willing to use a reliable method of barrier contraception (such as&#xD;
                  diaphragm or condoms), during the trial and for 30 days after trial&#xD;
                  completion/termination&#xD;
&#xD;
               4. Are breast-feeding&#xD;
&#xD;
          -  Use of any pharmacological contraceptive (including oral, patch or injectable&#xD;
             contraceptives) within 1 month prior to study initiation and for the duration of the&#xD;
             study&#xD;
&#xD;
          -  Use of hormone replacement therapy within 1 month prior to study initiation and for&#xD;
             the duration of the study&#xD;
&#xD;
          -  Participation in another trial with an investigational medicine within 60 days prior&#xD;
             to Day 0 (Visit 2)&#xD;
&#xD;
          -  Use of any prohibited medication listed in the protocol within 30 days prior to Day 0&#xD;
             (Visit 2)&#xD;
&#xD;
          -  Administration of antibiotics within 10 days prior to Day 0 (Visit 2) or during the&#xD;
             trial&#xD;
&#xD;
          -  History of acute illness within 60 days of trial initiation. Subjects are excluded for&#xD;
             these disorders greater than 60 days if, in the opinion of the investigator, the&#xD;
             subject does not qualify as a healthy volunteer&#xD;
&#xD;
          -  Serological evidence of hepatitis B (HBV) or hepatitis C (HCV)&#xD;
&#xD;
          -  Serological evidence of exposure to HIV&#xD;
&#xD;
          -  Recent history of alcohol or substance abuse (within 6 months of study period)&#xD;
&#xD;
          -  Blood or plasma donations within 30 days prior to Day 0 (Visit 2) or during the trial&#xD;
&#xD;
          -  Subjects with a seated systolic blood pressure either &lt;100 mm Hg or &gt;150 mm Hg&#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 (TPV), ritonavir (RTV) or clarithromycin (CLR) to the subject&#xD;
&#xD;
          -  Subjects who have taken, within 7 days prior to Day 0 (Visit 2), any over-the-counter&#xD;
             or prescription drugs that, in the opinion of the investigator in consultation with&#xD;
             the BI clinical monitor, might interfere with either the absorption, distribution or&#xD;
             metabolism of the test substances&#xD;
&#xD;
          -  Known hypersensitivity to TPV, RTV, sulfonamides, or CLR&#xD;
&#xD;
          -  Lactose intolerance or intolerance to high-fat foods&#xD;
&#xD;
          -  Allergies or intolerance to foods such as soybean, wheat, milk, eggs or gluten&#xD;
&#xD;
          -  Inability to adhere to requirements of the protocol&#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>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>Tipranavir</mesh_term>
    <mesh_term>Clarithromycin</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/NCT02251769
org study id: 1182.11
nct id: NCT02251769
lead sponsor: 
To determine the effects of single-dose and steady-state Tipranavir/Ritonavir (TPV/r) at 500
      mg/200 mg bid on the steady-state pharmacokinetics of clarithromycin and to determine the
      effects of a standard high-fat test meal on the steady-state pharmacokinetics of tipranavir.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under plasma concentration time curve from 0-12 hours (AUC0-12h)
time frame: up to 12 hours
measure: Maximum plasma concentration (Cmax)
time frame: up to 12 hours
measure: Plasma trough concentration (Cp12h)
time frame: up to 12 hours
measure: Oral clearance (CL/F)
time frame: up to 12 hours
measure: Volume of distribution (V)
time frame: up to 12 hours
measure: Apparent terminal half life (t1/2)
time frame: up to 12 hours
measure: Time of maximum concentration (Tmax)
time frame: up to 12 hours
measure: Mean Residency Time (MRT)
time frame: up to 12 hours
measure: Number of patients with adverse events
time frame: up to day 13
measure: Number of patients with clinically significant laboratory findings
time frame: up to day 13
arm group label: Sequential administration
arm group type: Experimental
intervention type: Drug
intervention name: Tipranavir
arm group label: Sequential administration
intervention type: Drug
intervention name: Ritonavir
arm group label: Sequential administration
intervention type: Drug
intervention name: Clarithromycin
arm group label: Sequential administration
intervention type: Other
intervention name: High-Fat Test Meal
arm group label: Sequential administration
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: Clarithromycin