<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/NCT02245438</url>
  </required_header>
  <id_info>
    <org_study_id>1182.22</org_study_id>
    <nct_id>NCT02245438</nct_id>
  </id_info>
  <brief_title>Effect of Tipranavir and Ritonavir on the Pharmacokinetic Characteristics of Norethindrone-Ethinyl Estradiol in Healthy Female Adult Volunteers</brief_title>
  <official_title>A Single Centre, Open-label, Randomized, Parallel Group, Multiple Dose Comparison of the Effect of TPV 750 mg and RTV 200 mg or TPV 500 mg and RTV 100 mg, Administered Twice Daily, on the Pharmacokinetic Characteristics of Norethindrone-Ethinyl Estradiol (Ortho®-1/35 ) Administered as a Single Dose, in Healthy Female 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>
      Study to characterize the effects of two dose combinations of Tipranavir (TPV)/Ritonavir&#xD;
      (RTV) (TPV 750 mg/RTV 200 mg and TPV 500 mg/RTV 100 mg), administered twice-daily, on the&#xD;
      pharmacokinetics of Norethindrone-Ethinyl Estradiol (NET/EE) 1 mg/ 0.035 mg administered as a&#xD;
      single dose.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>May 2002</start_date>
  <primary_completion_date type="Actual">June 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under plasma concentration time curve</measure>
    <time_frame>up to day 17</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration of the analyte</measure>
    <time_frame>up to day 17</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Drug concentration of the analyte in plasma at 12 hours after administration</measure>
    <time_frame>up to day 17</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oral clearance of the analyte</measure>
    <time_frame>up to day 17</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of maximum concentration of the analyte</measure>
    <time_frame>up to day 17</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half life of the analyte</measure>
    <time_frame>up to day 17</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 45 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subject with clinically relevant changes in laboratory parameters</measure>
    <time_frame>up to 17 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">52</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>Tipranavir low dose</intervention_name>
    <arm_group_label>TPV/RTV low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir high dose</intervention_name>
    <arm_group_label>TPV/RTV high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir low dose</intervention_name>
    <arm_group_label>TPV/RTV low dose</arm_group_label>
    <other_name>Norvir-SEC®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir high dose</intervention_name>
    <arm_group_label>TPV/RTV high dose</arm_group_label>
    <other_name>Norvir-SEC®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Norethindrone-Ethinyl Estradiol</intervention_name>
    <arm_group_label>TPV/RTV high dose</arm_group_label>
    <arm_group_label>TPV/RTV low dose</arm_group_label>
    <other_name>Ortho®-1/35</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female subjects between 18 and 50 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 large capsules without difficulty&#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. All abnormal laboratory values greater than Grade 1 are subject to&#xD;
             approval by the trial clinical monitor.&#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 for 48 hours prior to Study Day 0 and abstain from&#xD;
             alcohol for the duration of the study. In addition, red wine must not have been&#xD;
             ingested within 5 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          8. Willingness to abstain from ingesting grapefruit, grapefruit juice, or products&#xD;
             containing grapefruit juice, within 10 days before Day 0, Visit 2 and for the duration&#xD;
             of the study&#xD;
&#xD;
          9. 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 5 days of Day 0, Visit 2 and for the duration of&#xD;
             the study&#xD;
&#xD;
         10. Willingness to abstain from over the counter herbal medications for the duration of&#xD;
             the study&#xD;
&#xD;
         11. 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 beta-human chorionic gonadotropin at Visit 1, or on Day 0 or&#xD;
                  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 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&#xD;
&#xD;
               -  Are breast-feeding&#xD;
&#xD;
          2. Participation in another trial with an investigational medicine within 30 days prior&#xD;
             to Day 0 (Visit 2)&#xD;
&#xD;
          3. Use of any medication listed in the protocol within 30 days prior to Day 0 (Visit 2)&#xD;
&#xD;
          4. Use of any other 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;
          5. Administration of antibiotics within 10 days prior to Day 0 (Visit 2) or during the&#xD;
             trial&#xD;
&#xD;
          6. History of central nervous system (CNS), gastrointestinal, hepatic, or renal disorders&#xD;
             within the past sixty (60) days. Subjects will be excluded for these disorders greater&#xD;
             than sixty days if, in the opinion of the investigator, the subject does not qualify&#xD;
             as a healthy volunteer&#xD;
&#xD;
          7. History of thrombotic disease&#xD;
&#xD;
          8. History of migraine headache&#xD;
&#xD;
          9. Have serological evidence of hepatitis B or C virus&#xD;
&#xD;
         10. Have serological evidence of exposure to HIV&#xD;
&#xD;
         11. Recent history of alcohol or substance abuse (within 6 months of study period)&#xD;
&#xD;
         12. Cigarette smoking (greater than 10 cigarettes per day)&#xD;
&#xD;
         13. Blood or plasma donations within 30 days prior to Day 0 (Visit 2) or during the trial.&#xD;
&#xD;
         14. 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 a high fitness level, the investigator may discuss&#xD;
             exclusion with the medical monitor on a case-by-case basis&#xD;
&#xD;
         15. 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 NET/EE to the subject&#xD;
&#xD;
         16. Subjects who have had an acute illness within 2 weeks prior to Day 0 (Visit 2)&#xD;
&#xD;
         17. 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;
         18. Known hypersensitivity to TPV, RTV, or NET/EE&#xD;
&#xD;
         19. Inability to comply with the protocol&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 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>Ethinyl Estradiol</mesh_term>
    <mesh_term>Norethindrone</mesh_term>
    <mesh_term>Norethindrone Acetate</mesh_term>
    <mesh_term>Norinyl</mesh_term>
    <mesh_term>Estradiol</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/NCT02245438
org study id: 1182.22
nct id: NCT02245438
lead sponsor: 
Study to characterize the effects of two dose combinations of Tipranavir (TPV)/Ritonavir
      (RTV) (TPV 750 mg/RTV 200 mg and TPV 500 mg/RTV 100 mg), administered twice-daily, on the
      pharmacokinetics of Norethindrone-Ethinyl Estradiol (NET/EE) 1 mg/ 0.035 mg administered as a
      single dose.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under plasma concentration time curve
time frame: up to day 17
measure: Maximum plasma concentration of the analyte
time frame: up to day 17
measure: Drug concentration of the analyte in plasma at 12 hours after administration
time frame: up to day 17
measure: Oral clearance of the analyte
time frame: up to day 17
measure: Time of maximum concentration of the analyte
time frame: up to day 17
measure: Apparent terminal half life of the analyte
time frame: up to day 17
measure: Number of subjects with adverse events
time frame: up to 45 days
measure: Number of subject with clinically relevant changes in laboratory parameters
time frame: up to 17 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: Tipranavir low dose
arm group label: TPV/RTV low dose
intervention type: Drug
intervention name: Tipranavir high dose
arm group label: TPV/RTV high dose
intervention type: Drug
intervention name: Ritonavir low dose
arm group label: TPV/RTV low dose
other name: Norvir-SEC®
intervention type: Drug
intervention name: Ritonavir high dose
arm group label: TPV/RTV high dose
other name: Norvir-SEC®
intervention type: Drug
intervention name: Norethindrone-Ethinyl Estradiol
arm group label: TPV/RTV high dose
arm group label: TPV/RTV low dose
other name: Ortho®-1/35
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 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: Ethinyl Estradiol
mesh term: Norethindrone
mesh term: Norethindrone Acetate
mesh term: Norinyl
mesh term: Estradiol