<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/NCT02195466</url>
  </required_header>
  <id_info>
    <org_study_id>1182.10</org_study_id>
    <nct_id>NCT02195466</nct_id>
  </id_info>
  <brief_title>Effects of Single-dose and Steady-state TPV/RTV on the Steady-state Pharmacokinetics of Fluconazole in Healthy Adult Volunteers</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/RTV 500/200 mg on the Steady-state Pharmacokinetics of Fluconazole 100 mg qd (200 mg Loading Dose)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Study to determine the effects of single-dose and steady-state TPV/RTV 500/200 mg on the&#xD;
      steady-state pharmacokinetics of fluconazole&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2003</start_date>
  <primary_completion_date type="Actual">July 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 0-24 hours (AUC0-24h) for FCZ</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax) for FCZ</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration in plasma at 24 hours after administration (Cp24h) for FCZ</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-12h for TPV</measure>
    <time_frame>up to 12 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax for TPV</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug concentration in plasma at 12 hours after administration (Cp12h) for TPV</measure>
    <time_frame>up to 12 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (Cl/F) for FCZ and TPV</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum concentration (tmax) for FCZ and TPV</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half life (t1/2) for FCZ and TPV</measure>
    <time_frame>up to 24 hours after administration of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 6 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV + RTV + FCZ</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir (TPV)</intervention_name>
    <description>500 mg bid on days 7-14</description>
    <arm_group_label>TPV + RTV + FCZ</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir (RTV)</intervention_name>
    <description>200 mg bid on days 7-14</description>
    <arm_group_label>TPV + RTV + FCZ</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluconazole (FCZ)</intervention_name>
    <description>200 mg loading dose on day 1, followed by 100 mg qd until day 13</description>
    <arm_group_label>TPV + RTV + FCZ</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 large capsules without difficulty&#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 is less than or equal to Grade 1, based on the AIDS Clinical Trials Group&#xD;
             (ACTG) Grading Scale. All abnormal laboratory values greater than Grade 1 are subject&#xD;
             to approval by the trial clinical monitor&#xD;
&#xD;
          -  Acceptable medical history, physical examination, 12-lead electrocardiogram, and chest&#xD;
             X-ray (if not conducted within the last 12 months and deemed necessary by&#xD;
             investigator) are required prior to entering the treatment phase of the study&#xD;
&#xD;
          -  Willingness to abstain from the following starting 14 days prior to any administration&#xD;
             of study drugs up until the end of the study:&#xD;
&#xD;
               -  Grapefruit or grapefruit juice&#xD;
&#xD;
               -  Red wine&#xD;
&#xD;
               -  Seville oranges&#xD;
&#xD;
               -  St. John's Wort or Milk Thistle&#xD;
&#xD;
          -  Willingness to abstain from alcohol starting 2 days prior to administration study drug&#xD;
             up to the end of the study&#xD;
&#xD;
          -  Willingness to abstain from the following within 72 hours of pharmacokinetics (PK)&#xD;
             sampling:&#xD;
&#xD;
               -  Garlic supplements&#xD;
&#xD;
               -  Methylxanthine containing drinks (coffee, tea, cola, energy drinks, chocolate,&#xD;
                  etc.)&#xD;
&#xD;
          -  Willingness to abstain from over the counter herbal medications for the duration of&#xD;
             the study&#xD;
&#xD;
          -  Have been non-smokers for 3 months&#xD;
&#xD;
          -  Willingness to abstain from vigorous physical exercise during intensive PK Days 6, 7,&#xD;
             13&#xD;
&#xD;
          -  Reasonable probability for completion of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female subjects who are of reproductive potential and:&#xD;
&#xD;
               -  Have a positive serum β-human chorionic gonadotropin (hCG) at Visit 1, or on Day&#xD;
                  0 or Day 1&#xD;
&#xD;
               -  Have not been using a barrier contraceptive method for at least 3 months prior to&#xD;
                  Visit 3 (Day 1)&#xD;
&#xD;
               -  Are not willing to use a reliable method of barrier contraception (such as&#xD;
                  diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during&#xD;
                  the trial and 60 days after completion/termination&#xD;
&#xD;
               -  Are breast-feeding&#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;
          -  Use of any pharmacological contraceptive (including oral, patch or injectable&#xD;
             contraceptives) within 1 month of study initiation and for the duration of the study.&#xD;
             Use of Depo-Provera is excluded for six months prior to study initiation&#xD;
&#xD;
          -  Use of hormone replacement therapy within 1 month of study initiation and for the&#xD;
             duration of the study&#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 the past 60 days. Subjects will be excluded for these&#xD;
             disorders greater than sixty days if, in the opinion of the investigator, the subject&#xD;
             does not qualify as a healthy volunteer&#xD;
&#xD;
          -  History of thrombotic disease&#xD;
&#xD;
          -  History of migraine headache&#xD;
&#xD;
          -  Have serological evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV)&#xD;
&#xD;
          -  Have serological evidence of exposure to HIV&#xD;
&#xD;
          -  Recent history of alcohol or substance abuse (within 1 year of study period)&#xD;
&#xD;
          -  Blood or plasma donations within 30 days of 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;
             resting heart rate either &lt;50 beats/min or &gt;90 beats/min. For subjects with a resting&#xD;
             heart rate below 50, or above 90, the investigator may discuss exclusion with the&#xD;
             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 TPV, RTV or FCZ to the subject&#xD;
&#xD;
          -  Subjects who have had an acute illness within 2 weeks prior to Day 0 (Visit 2)&#xD;
&#xD;
          -  Subjects who are currently taking any over-the-counter or prescription drug within 7&#xD;
             days prior to Day 0 (Visit 2) that, in the opinion of the investigator in consultation&#xD;
             with the Boehringer Ingelheim (Canada) Ltd./Ltée clinical monitor, might interfere&#xD;
             with either the absorption, distribution or metabolism of the test substances&#xD;
&#xD;
          -  Known hypersensitivity to TPV, RTV, FCZ, or sulphonamide class of drugs&#xD;
&#xD;
          -  Inability to adhere to the protocol&#xD;
&#xD;
          -  Cautions or warnings in the FCZ package insert which, in the judgment of the&#xD;
             investigator, should exclude a subject from the study&#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/content/dam/internet/opu/clinicaltrial/com_EN/results/1182/1182.10_U04-3100.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>July 18, 2014</last_update_submitted>
  <last_update_submitted_qc>July 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 21, 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>Fluconazole</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/NCT02195466
org study id: 1182.10
nct id: NCT02195466
lead sponsor: 
Study to determine the effects of single-dose and steady-state TPV/RTV 500/200 mg on the
      steady-state pharmacokinetics of fluconazole
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under plasma concentration time curve from 0-24 hours (AUC0-24h) for FCZ
time frame: up to 24 hours after administration of study drug
measure: Maximum plasma concentration (Cmax) for FCZ
time frame: up to 24 hours after administration of study drug
measure: Drug concentration in plasma at 24 hours after administration (Cp24h) for FCZ
time frame: up to 24 hours after administration of study drug
measure: AUC0-12h for TPV
time frame: up to 12 hours after administration of study drug
measure: Cmax for TPV
time frame: up to 24 hours after administration of study drug
measure: Drug concentration in plasma at 12 hours after administration (Cp12h) for TPV
time frame: up to 12 hours after administration of study drug
measure: Oral clearance (Cl/F) for FCZ and TPV
time frame: up to 24 hours after administration of study drug
measure: Time of maximum concentration (tmax) for FCZ and TPV
time frame: up to 24 hours after administration of study drug
measure: Apparent terminal half life (t1/2) for FCZ and TPV
time frame: up to 24 hours after administration of study drug
measure: Number of patients with adverse events
time frame: up to 6 weeks
arm group label: TPV + RTV + FCZ
arm group type: Experimental
intervention type: Drug
intervention name: Tipranavir (TPV)
description: 500 mg bid on days 7-14
arm group label: TPV + RTV + FCZ
intervention type: Drug
intervention name: Ritonavir (RTV)
description: 200 mg bid on days 7-14
arm group label: TPV + RTV + FCZ
intervention type: Drug
intervention name: Fluconazole (FCZ)
description: 200 mg loading dose on day 1, followed by 100 mg qd until day 13
arm group label: TPV + RTV + FCZ
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/1182/1182.10_U04-3100.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Ritonavir
mesh term: Tipranavir
mesh term: Fluconazole