<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/NCT02253823</url>
  </required_header>
  <id_info>
    <org_study_id>1182.41</org_study_id>
    <nct_id>NCT02253823</nct_id>
  </id_info>
  <brief_title>Multiple Dose Comparison of the Effect of Two Dose Combinations of Tipranavir/Ritonavir (TPV/RTV), on the Pharmacokinetic Characteristics of Efavirenz (Sustiva®) in Healthy Adult Volunteers</brief_title>
  <official_title>A Single Center, Open-Label, Randomised, Parallel, Multiple Dose Comparison of the Effect of Tipranavir 500 mg and Ritonavir 100 mg or Tipranavir 750 mg and Ritonavir 200 mg, Administered Daily on 3 Non-Consecutive Days and Twice Daily for 7 Days, on the Pharmacokinetic Characteristics of Efavirenz (Sustiva®) 600 mg a Day in Healthy Adult 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 was to characterize the effects of two dose combinations of&#xD;
      tipranavir/ritonavir (TPV 500 mg/RTV 100 mg and TPV 750 mg/RTV 200 mg), administered daily&#xD;
      and BID, on the pharmacokinetics of efavirenz (EFV), 600 mg daily&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2001</start_date>
  <primary_completion_date type="Actual">March 2002</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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax (Maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC 0-12 (Area under the plasma concentration time curve from 0-12 hours)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cp12h (observed drug concentration in plasma at 12 hours)</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC 0-24 (Area under the plasma concentration time curve from 0-24 hours)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cp24h (observed drug concentration in plasma at 24 hours)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>CL/F (Apparent clearance of the analyte in plasma following extravascular administration)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>V (Volume of distribution)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax (Time from dosing to the maximum concentration of the analyte in plasma)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t½ (Terminal half-life of the analyte in plasma)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 43 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 43 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV+RTV - low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV+RTV - high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EFV</intervention_name>
    <arm_group_label>TPV+RTV - high dose</arm_group_label>
    <arm_group_label>TPV+RTV - low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV/RTV - low dose</intervention_name>
    <arm_group_label>TPV+RTV - low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV/RTV - high dose</intervention_name>
    <arm_group_label>TPV+RTV - high dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability and willingness to give written informed consent in accordance with&#xD;
             institutional and federal guidelines and to comply with the investigational nature of&#xD;
             the study and the related requirements&#xD;
&#xD;
          -  Healthy males or females between 18 and 60 years of age inclusive&#xD;
&#xD;
          -  Ability to swallow numerous large capsules without difficulty&#xD;
&#xD;
          -  Reasonable probability for completion of the study&#xD;
&#xD;
          -  A Body Mass Index (BMI) between 18 and 35 kg/m2&#xD;
&#xD;
          -  Acceptable laboratory values that indicate adequate baseline organ function are&#xD;
             required at the time of screening. Laboratory values are considered to be acceptable&#xD;
             if severity ≤ Grade 1 based on the Adult AIDS Clinical Trial Group (ACTG) Division of&#xD;
             Acquired Immunodeficiency Syndrome (of the National Institute of Allergy and&#xD;
             Infectious Diseases / National Institutes of Health) (DAIDS) Grading Scale. All&#xD;
             abnormal laboratory values &gt; Grade 1 (e.g., creatine phosphokinase (CPK), amylase,&#xD;
             triglycerides) are subject to approval by the Boehringer Ingelheim Pharmaceuticals,&#xD;
             Inc. (BIPI) clinical monitor&#xD;
&#xD;
          -  Acceptable medical history, physical examination, ECG, and Chest X-ray are required&#xD;
             prior to entering 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, Cabernet Sauvignon must not have&#xD;
             been ingested within 15 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          -  Willingness to abstain from ingesting grapefruit and grapefruit juice within 15 days&#xD;
             of Day 0, Visit 2 and for the duration of the study&#xD;
&#xD;
          -  Willingness to abstain from ingesting Seville oranges, garlic supplements, St. John's&#xD;
             Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee, tea, cola,&#xD;
             energy drinks, chocolate, etc.) within 72 hours of PK sampling days [Visit 3 (Days&#xD;
             1-6), Visit 4 (Days 12-15), Visit 5 (Days 20-21 and Visit 6 (Day 22)]&#xD;
&#xD;
          -  Willingness to abstain from use of tobacco products for the duration of the study&#xD;
&#xD;
          -  Urine drug screen negative for illegal non-prescription drugs&#xD;
&#xD;
          -  Negative HIV serology&#xD;
&#xD;
          -  Negative for Hepatitis B surface antigen and Hepatitis C&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects who are of reproductive potential who:&#xD;
&#xD;
               -  Have a positive serum B-human chronic gonadotropin (HCG) at Visit 1 or,&#xD;
&#xD;
               -  Have not been using a barrier contraceptive method for at least 3 months prior to&#xD;
                  Visit 3 (Day 1), or&#xD;
&#xD;
               -  Are not willing to use a reliable method of double-barrier contraception (such as&#xD;
                  diaphragm with spermicidal cream/jelly or condoms with spermicidal foam) during&#xD;
                  the trial and 30 days after completion/termination or,&#xD;
&#xD;
               -  Are breast-feeding&#xD;
&#xD;
          -  Participation in another trial with an investigational medicine for 30 days prior to&#xD;
             Day 0 (Visit 2)&#xD;
&#xD;
          -  Use of any known enzyme altering drug (such as phenothiazines, cimetidine,&#xD;
             barbiturates, ketoconazole, fluconazole, rifampin, steroids, and herbal medications&#xD;
             within 30 days prior to Day 0 (Visit 2) or during the trial&#xD;
&#xD;
          -  Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within 15 days prior&#xD;
             to Day 0 (Visit 2)&#xD;
&#xD;
          -  Ingestion of Seville oranges, garlic supplements, St. John's Wort, Milk Thistle, or&#xD;
             methylxanthine-containing drinks or food (coffee, tea, cola, energy drinks, chocolate,&#xD;
             etc.) within 72 hours of pharmacokinetics (PK) sampling days [Visit 3 (Days 1-6),&#xD;
             Visit 4 (Days 12-15), Visit 5 (Days 20-21 and Visit 6 (Day 22)]&#xD;
&#xD;
          -  Administration of antibiotics within 10 days prior to Day 0 (Visit 2) or during the&#xD;
             trial&#xD;
&#xD;
          -  Inability to comply with investigator's instructions&#xD;
&#xD;
          -  History of central nervous system (CNS), gastrointestinal, hepatic, or renal disorders&#xD;
             within the past 60 days. Subjects were excluded for these disorders greater than sixty&#xD;
             days, if in the opinion of the investigator, the subject did not qualify as a healthy&#xD;
             volunteer&#xD;
&#xD;
          -  History of alcohol abuse&#xD;
&#xD;
          -  Excessive cigarettes smoking defined as greater than 10 cigarettes per day&#xD;
&#xD;
          -  Blood or plasma donations within 30 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          -  Subjects with a seated systolic blood pressure either &lt;100 mm Hg or &gt;150 mm Hg;&#xD;
             resting heart rate either &lt;50 beats/min or &gt;90 beats/min. For subjects with a resting&#xD;
             heart rate below 50, due to high fitness level, the investigator could discuss&#xD;
             exclusion with medical monitor on a case-by-case basis&#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, ritonavir or efavirenz to the subject&#xD;
&#xD;
          -  Subjects who have an acute illness within 2 weeks prior to Day 0 (Visit 2).&#xD;
&#xD;
          -  Subjects who are taking any over-the-counter drug within 7 days prior to Day 0, (Visit&#xD;
             2) or are taking any prescription drug that, in the opinion of the investigator in&#xD;
             consultation with the BIPI clinical monitor and pharmacokineticist, might interfere&#xD;
             with either the absorption, distribution or metabolism of the test substances&#xD;
&#xD;
          -  Subjects suffering from active forms of depression&#xD;
&#xD;
          -  Subjects that had a history of suicidal ideations&#xD;
&#xD;
          -  Known hypersensitivity to tipranavir, ritonavir, or efavirenz&#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 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>September 29, 2014</last_update_submitted>
  <last_update_submitted_qc>September 29, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 1, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT02253823
org study id: 1182.41
nct id: NCT02253823
lead sponsor: 
The objective of this study was to characterize the effects of two dose combinations of
      tipranavir/ritonavir (TPV 500 mg/RTV 100 mg and TPV 750 mg/RTV 200 mg), administered daily
      and BID, on the pharmacokinetics of efavirenz (EFV), 600 mg daily
allocation: Randomized
intervention model: Parallel Assignment
masking: None (Open Label)
measure: Cmax (Maximum measured concentration of the analyte in plasma)
time frame: up to 24 hours after drug administration
measure: AUC 0-12 (Area under the plasma concentration time curve from 0-12 hours)
time frame: up to 12 hours after drug administration
measure: Cp12h (observed drug concentration in plasma at 12 hours)
time frame: up to 12 hours after drug administration
measure: AUC 0-24 (Area under the plasma concentration time curve from 0-24 hours)
time frame: up to 24 hours after drug administration
measure: Cp24h (observed drug concentration in plasma at 24 hours)
time frame: up to 24 hours after drug administration
measure: CL/F (Apparent clearance of the analyte in plasma following extravascular administration)
time frame: up to 24 hours after drug administration
measure: V (Volume of distribution)
time frame: up to 24 hours after drug administration
measure: Tmax (Time from dosing to the maximum concentration of the analyte in plasma)
time frame: up to 24 hours after drug administration
measure: t½ (Terminal half-life of the analyte in plasma)
time frame: up to 24 hours after drug administration
measure: Number of subjects with adverse events
time frame: up to 43 days
measure: Number of subjects with abnormal changes in laboratory parameters
time frame: up to 43 days
arm group label: TPV+RTV - low dose
arm group type: Experimental
arm group label: TPV+RTV - high dose
arm group type: Experimental
intervention type: Drug
intervention name: EFV
arm group label: TPV+RTV - high dose
arm group label: TPV+RTV - low dose
intervention type: Drug
intervention name: TPV/RTV - low dose
arm group label: TPV+RTV - low dose
intervention type: Drug
intervention name: TPV/RTV - high dose
arm group label: TPV+RTV - high dose
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