<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/NCT02245269</url>
  </required_header>
  <id_info>
    <org_study_id>1182.21</org_study_id>
    <nct_id>NCT02245269</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Atorvastatin With Tipranavir/Ritonavir and the Effect of Antacid on the Pharmacokinetics of Single-Dose Tipranavir/Ritonavir in Healthy Volunteers</brief_title>
  <official_title>A Two-way Pharmacokinetic Interaction Study of Single-Dose Atorvastatin (LIPITOR®) With Tipranavir/Ritonavir (500mg/200mg) at Steady-State and the Effect of Antacid (MAALOX®) on the Pharmacokinetics of Single-Dose Tipranavir/Ritonavir (500mg/200mg) in 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>
      Study to determine the effects of combined tipranavir and ritonavir treatment (at&#xD;
      steady-state) on the single-dose pharmacokinetics of atorvastatin, the effects of single-dose&#xD;
      atorvastatin on the steady-state pharmacokinetics of tipranavir, and the effects of antacid&#xD;
      on the pharmacokinetics of tipranavir&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2003</start_date>
  <primary_completion_date type="Actual">October 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 the plasma drug concentration-time curve from time zero to infinity of the analyte (AUC0-∞)</measure>
    <time_frame>up to day 22</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration of the analyte (Cmax)</measure>
    <time_frame>up to day 22</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration of the analyte in plasma at 12 hours after administration (Cp12h)</measure>
    <time_frame>up to day 22</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-12 hours of the analyte</measure>
    <time_frame>up to day 22</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oral clearance (CL/F)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution (V)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum concentration (tmax)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half life (t1/2)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Residence Time (MRT)</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hepatic cytochrome P450 3A4 activity using the Erythromycin Breath Test</measure>
    <time_frame>Days 7-10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in laboratory tests</measure>
    <time_frame>up to day 22</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV/r + Atorvastatin followed by TPV/r + antacid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Day 1: first dose of ATV Day 8: single dose of TPV/r Day 13: single dose of TPV/r, followed by a single dose of Maalox Days 14-21: morning and evening doses of TPV/r on Day 20: second dose of ATV</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <arm_group_label>TPV/r + Atorvastatin followed by TPV/r + antacid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>TPV/r + Atorvastatin followed by TPV/r + antacid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin</intervention_name>
    <arm_group_label>TPV/r + Atorvastatin followed by TPV/r + antacid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Maalox</intervention_name>
    <description>Aluminum Hydroxide; Magnesium Hydroxide; Simethicone</description>
    <arm_group_label>TPV/r + Atorvastatin followed by TPV/r + antacid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female subjects between 18 and 60 years of age inclusive&#xD;
&#xD;
          2. A Body Mass Index (BMI) between 18 and 29 kg/m2&#xD;
&#xD;
          3. Signed informed consent prior to trial participation&#xD;
&#xD;
          4. Ability to swallow numerous study medications&#xD;
&#xD;
          5. 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;
             Grading Scale&#xD;
&#xD;
          6. Acceptable medical history, physical examination and ECG, and chest X-ray (if not&#xD;
             conducted within the last 12 months) are required prior to entering the treatment&#xD;
             phase of the study&#xD;
&#xD;
          7. Willingness to abstain from alcohol starting 2 days prior to any administration study&#xD;
             drug up to the end of the study. Red wine must not be ingested within 5 days prior to&#xD;
             treatment and throughout the study&#xD;
&#xD;
          8. Willingness to abstain from the following starting 10 days prior to any administration&#xD;
             of study drug up until the end of the study:&#xD;
&#xD;
             • Grapefruit or grapefruit juice or products containing grapefruit juice&#xD;
&#xD;
          9. Willingness to abstain from ingesting Seville oranges, garlic supplements, St. John's&#xD;
             Wort, or Milk Thistle, within 5 days of treatment and for the duration of the study&#xD;
&#xD;
         10. Willingness to abstain from methylxanthine-containing drinks or foods (coffee, tea,&#xD;
             cola, energy drinks, chocolate, etc.) within 72 hours of each pharmacokinetic (PK)&#xD;
             sampling day and until after the last sample from each of the intensive sampling days&#xD;
             is collected&#xD;
&#xD;
         11. Willingness to abstain from over the counter herbal medications for the duration of&#xD;
             the study&#xD;
&#xD;
         12. Willingness to abstain from vigorous physical exercise during PK Days&#xD;
&#xD;
         13. Reasonable probability for completion of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female subjects who are of reproductive potential who:&#xD;
&#xD;
               -  Have positive serum β-human chorionic gonadotropin at Visit 1, or on Day 0&#xD;
&#xD;
               -  Have not been using a barrier contraceptive method for at least 3 months prior to&#xD;
                  Day 0 (Visit 2)&#xD;
&#xD;
               -  Are not willing to use a reliable method of barrier contraception (such as&#xD;
                  diaphragm or condoms), during the trial and 30 days after completion/termination&#xD;
&#xD;
               -  Are breast-feeding&#xD;
&#xD;
          2. Use of any pharmacological contraceptive (including oral, patch or injectable&#xD;
             contraceptives) for 1 month prior to study initiation and for the duration of the&#xD;
             study&#xD;
&#xD;
          3. Use of hormone replacement therapy for 1 month prior to study initiation and for the&#xD;
             duration of the study&#xD;
&#xD;
          4. Participation in another trial with an investigational medicine within 60 days prior&#xD;
             to Day 0 (Visit 2)&#xD;
&#xD;
          5. Use of any medication listed in the protocol within 30 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          6. Administration of antibiotics within 10 days prior to Day 0 (Visit 2) or during the&#xD;
             trial&#xD;
&#xD;
          7. History of acute illness within the past sixty (60) days. Subjects will be excluded&#xD;
             for these disorders greater than sixty days if, in the opinion of the investigator,&#xD;
             the subject does not qualify as a healthy volunteer&#xD;
&#xD;
          8. Have serological evidence of Hepatitis B or C Virus&#xD;
&#xD;
          9. Have serological evidence of exposure to HIV&#xD;
&#xD;
         10. Recent history of alcohol or substance abuse (within 6 months of study period)&#xD;
&#xD;
         11. Smokers who smoke greater than 10 cigarettes or 3 cigars or 3 pipes per day; inability&#xD;
             to refrain from smoking during the trial&#xD;
&#xD;
         12. Blood or plasma donations within 30 days prior to Day 0 (Visit 2) or during the trial&#xD;
&#xD;
         13. 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&#xD;
&#xD;
         14. 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, atorvastatin or erythromycin to the subject&#xD;
&#xD;
         15. Subjects who are currently taking any over-the-counter drug within 7 days prior to Day&#xD;
             0,(Visit 2) or who are currently taking any prescription drug that, in the opinion of&#xD;
             the investigator in consultation with the clinical monitor, might interfere with&#xD;
             either the absorption, distribution or metabolism of the test substances&#xD;
&#xD;
         16. Known hypersensitivity to Tipranavir,Ritonavir, sulfonamides, atorvastatin,&#xD;
             erythromycin or saccharin&#xD;
&#xD;
         17. Inability to comply with the protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>22 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 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>September 18, 2014</last_update_submitted>
  <last_update_submitted_qc>September 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 19, 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>Atorvastatin</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/NCT02245269
org study id: 1182.21
nct id: NCT02245269
lead sponsor: 
Study to determine the effects of combined tipranavir and ritonavir treatment (at
      steady-state) on the single-dose pharmacokinetics of atorvastatin, the effects of single-dose
      atorvastatin on the steady-state pharmacokinetics of tipranavir, and the effects of antacid
      on the pharmacokinetics of tipranavir
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the plasma drug concentration-time curve from time zero to infinity of the analyte (AUC0-∞)
time frame: up to day 22
measure: Maximum plasma concentration of the analyte (Cmax)
time frame: up to day 22
measure: Drug concentration of the analyte in plasma at 12 hours after administration (Cp12h)
time frame: up to day 22
measure: AUC0-12 hours of the analyte
time frame: up to day 22
measure: Oral clearance (CL/F)
time frame: up to day 22
measure: Volume of distribution (V)
time frame: up to day 22
measure: Time of maximum concentration (tmax)
time frame: up to day 22
measure: Apparent terminal half life (t1/2)
time frame: up to day 22
measure: Mean Residence Time (MRT)
time frame: up to day 22
measure: Hepatic cytochrome P450 3A4 activity using the Erythromycin Breath Test
time frame: Days 7-10
measure: Number of patients with adverse events
time frame: up to day 22
measure: Number of patients with clinically relevant changes in laboratory tests
time frame: up to day 22
arm group label: TPV/r + Atorvastatin followed by TPV/r + antacid
arm group type: Experimental
description: Day 1: first dose of ATV Day 8: single dose of TPV/r Day 13: single dose of TPV/r, followed by a single dose of Maalox Days 14-21: morning and evening doses of TPV/r on Day 20: second dose of ATV
intervention type: Drug
intervention name: Tipranavir
arm group label: TPV/r + Atorvastatin followed by TPV/r + antacid
intervention type: Drug
intervention name: Ritonavir
arm group label: TPV/r + Atorvastatin followed by TPV/r + antacid
intervention type: Drug
intervention name: Atorvastatin
arm group label: TPV/r + Atorvastatin followed by TPV/r + antacid
intervention type: Drug
intervention name: Maalox
description: Aluminum Hydroxide; Magnesium Hydroxide; Simethicone
arm group label: TPV/r + Atorvastatin followed by TPV/r + antacid
criteria: 
gender: All
minimum age: 18 Years
maximum age: 22 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: Atorvastatin