<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/NCT02253888</url>
  </required_header>
  <id_info>
    <org_study_id>1182.93</org_study_id>
    <nct_id>NCT02253888</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Tipranavir Stored at Controlled Temperature Compared With Tipranavir Stored at Controlled Refrigerated Conditions, Orally Co-administered With Ritonavir in Healthy Male and Female Volunteers</brief_title>
  <official_title>An Open-label, Randomized, Single-dose, Two-way Crossover Bioequivalence Study Assessing Subjects Receiving Tipranavir 500 mg Stored at Controlled Temperature (Testproduct 30°C/70% RH) Compared With Tipranavir 500 mg Stored at Controlled Refrigerated Conditions (Reference Product 2-8°C), Orally Co-administered With Ritonavir 200 mg Under Fasting Conditions to Healthy Male and Female 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 trial was to establish the bioequivalence of Tipranavir (TPV) 250 mg&#xD;
      self emulsifying drug delivery system (SEDDS) capsules that had been stored at a controlled&#xD;
      temperature of 30°C and controlled relative humidity (RH) of 70% in comparison with TPV 250&#xD;
      mg SEDDS capsules stored at controlled refrigerated conditions between 2°C and 8°C&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2005</start_date>
  <primary_completion_date type="Actual">June 2005</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to infinity)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum measured concentration of the analyte in plasma)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under concentration-time curve of the analyte in plasma over the time interval of 0 to time of last quantifiable data point)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-72 (area under concentration-time curve of the analyte in plasma over the time interval t0h to t72h)</measure>
    <time_frame>up to 72 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 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant in plasma)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life of the analyte in plasma)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo (mean residence time of the analyte in the body after oral administration)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance of the analyte in the plasma after extravascular administration)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz after an extravascular dose)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 11 days after last dose of drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 11 days after last dose of drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV/r - Room condition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>TPV/r - Refrigerated conditions</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV - Room condition</intervention_name>
    <arm_group_label>TPV/r - Room condition</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPV - Refrigerated conditions</intervention_name>
    <arm_group_label>TPV/r - Refrigerated conditions</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir (RTV)</intervention_name>
    <arm_group_label>TPV/r - Refrigerated conditions</arm_group_label>
    <arm_group_label>TPV/r - Room condition</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy males and females with a complete medical history, including physical&#xD;
             examination, vital signs (BP, PR), 12-lead ECG and clinical laboratory tests that&#xD;
             have:&#xD;
&#xD;
               -  No findings that are abnormal or of clinical relevance&#xD;
&#xD;
               -  No evidence of a clinically relevant concomitant disease&#xD;
&#xD;
               -  Acceptable laboratory values that indicate adequate baseline organ function at&#xD;
                  time of screening. Laboratory values are considered acceptable if the severity is&#xD;
                  less than or equal to Grade 1, according to the AIDS Clinical Trials Group (ACTG)&#xD;
                  Division of Acquired Immunodeficiency Syndrome (of the National Institute of&#xD;
                  Allergy and Infectious Diseases / National Institutes of Health) (DAIDS) Grading&#xD;
                  Scale and within normal reference ranges for other laboratory parameters not&#xD;
                  defined by DAIDS. Participation of subjects with abnormal laboratory values&#xD;
                  greater than Grade 1 (e.g., Creatine phosphokinase (CPK), amylase, triglycerides)&#xD;
                  is subject to approval by the Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI)&#xD;
                  clinical monitor&#xD;
&#xD;
          2. Age ≥18 and ≤60 years&#xD;
&#xD;
          3. Body mass index (BMI) ≥18.5 and ≤35.0 kg/m2&#xD;
&#xD;
          4. Signed and dated written informed consent before admission to the study, in accordance&#xD;
             with Good Clinical Practice (GCP) and local legislation concerning volunteers who are&#xD;
             capable of understanding and giving informed consent&#xD;
&#xD;
          5. Willingness of subjects to abstain from ingesting the following foods and substances&#xD;
             beginning 2 weeks before administration of any study medication and until the end of&#xD;
             the study: grapefruit or grapefruit juice, red wine, Seville oranges, St. John's Wort&#xD;
             and Milk Thistle&#xD;
&#xD;
          6. Willingness of subjects to abstain from use of alcohol within 72 hours before&#xD;
             administration of study medication and to the end of the study&#xD;
&#xD;
          7. Willingness of subjects to abstain from the following substances within 72 hours&#xD;
             before administration of study medication: garlic supplements and methylxanthine&#xD;
             containing foods or drinks (including coffee, tea, cola, energy drinks, chocolate,&#xD;
             etc.)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Chronic gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          2. Surgery of gastrointestinal tract (except appendectomy)&#xD;
&#xD;
          3. Diseases of the central nervous system (such as epilepsy, cerebral cramps) or&#xD;
             psychiatric disorders or neurological disorders&#xD;
&#xD;
          4. History of relevant orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          5. Chronic or relevant acute infections&#xD;
&#xD;
          6. History of allergies or hypersensitivity (including drug allergies) that are deemed&#xD;
             relevant to the trial, as judged by the investigator&#xD;
&#xD;
          7. Intake of drugs with a long half-life (&gt;24 hours) within 1 month or less than 10&#xD;
             half-lives of the drug before administration of study drug or during the trial&#xD;
&#xD;
          8. Use of drugs that might reasonably influence the results of the trial (based on&#xD;
             knowledge at the time of the protocol's preparation) within 10 days before&#xD;
             administration of study drug or during the trial&#xD;
&#xD;
          9. Participation in another trial with an investigational drug within 30 days before&#xD;
             administration of study drug or during the trial.&#xD;
&#xD;
         10. Smoker (more than 10 cigarettes per day, 3 cigars per day or 3 pipes per day)&#xD;
&#xD;
         11. Inability to refrain from smoking 24 hours before receiving study medication and on&#xD;
             trial days when pharmacokinetic (PK) data are collected&#xD;
&#xD;
         12. High level of alcohol use (more than 60 grams per day)&#xD;
&#xD;
         13. Illicit drug use (i.e., positive urine test for illicit prescription or&#xD;
             non-prescription drugs or drugs of abuse)&#xD;
&#xD;
         14. Veins unsuited for i.v. puncture on either arm (e.g., veins that are difficult to&#xD;
             locate, access or puncture veins with a tendency to rupture during or after puncture)&#xD;
&#xD;
         15. Blood donation (more than 100 mL within 4 weeks before administration of study&#xD;
             medication or during the trial)&#xD;
&#xD;
         16. History of any bleeding disorder or acute blood coagulation defect&#xD;
&#xD;
         17. Hypersensitivity to RTV or related antiretroviral drugs&#xD;
&#xD;
         18. Extreme physical activities (within 1 week before administration of study medication&#xD;
             or during the trial)&#xD;
&#xD;
         19. Any laboratory value outside the reference range or &gt;DAIDS Grade 1 that is of clinical&#xD;
             relevance&#xD;
&#xD;
         20. Heart rate at screening of &gt;90 bpm or &lt;45 bpm&#xD;
&#xD;
         21. Seated systolic blood pressure either &lt;95 mm Hg or &gt;160 mm Hg&#xD;
&#xD;
         22. Any screening ECG value outside of the reference range of clinical relevance&#xD;
&#xD;
         23. Inability to adhere to dietary regimen of the study centre&#xD;
&#xD;
         24. For female subjects:&#xD;
&#xD;
               -  Pregnancy or planning to become pregnant within 60 days of study completion&#xD;
&#xD;
               -  Positive pregnancy test&#xD;
&#xD;
               -  Non-use of a barrier method of contraception for at least 3 months before&#xD;
                  participation in the study&#xD;
&#xD;
               -  Not willing or unable to use a reliable method of barrier contraception (such as&#xD;
                  diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during&#xD;
                  and up to 2 months after completion/termination of the trial&#xD;
&#xD;
               -  Chronic use of oral contraception or hormone replacement containing ethinyl&#xD;
                  estradiol&#xD;
&#xD;
               -  Breast-feeding&#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 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>September 30, 2014</last_update_submitted>
  <last_update_submitted_qc>September 30, 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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ritonavir</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/NCT02253888
org study id: 1182.93
nct id: NCT02253888
lead sponsor: 
The objective of this trial was to establish the bioequivalence of Tipranavir (TPV) 250 mg
      self emulsifying drug delivery system (SEDDS) capsules that had been stored at a controlled
      temperature of 30°C and controlled relative humidity (RH) of 70% in comparison with TPV 250
      mg SEDDS capsules stored at controlled refrigerated conditions between 2°C and 8°C
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to infinity)
time frame: up to 72 hours after drug administration
measure: Cmax (maximum measured concentration of the analyte in plasma)
time frame: up to 72 hours after drug administration
measure: AUC0-tz (area under concentration-time curve of the analyte in plasma over the time interval of 0 to time of last quantifiable data point)
time frame: up to 72 hours after drug administration
measure: AUC0-72 (area under concentration-time curve of the analyte in plasma over the time interval t0h to t72h)
time frame: up to 72 hours after drug administration
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma)
time frame: up to 72 hours after drug administration
measure: λz (terminal rate constant in plasma)
time frame: up to 72 hours after drug administration
measure: t1/2 (terminal half-life of the analyte in plasma)
time frame: up to 72 hours after drug administration
measure: MRTpo (mean residence time of the analyte in the body after oral administration)
time frame: up to 72 hours after drug administration
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
time frame: up to 72 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz after an extravascular dose)
time frame: up to 72 hours after drug administration
measure: Number of subjects with adverse events
time frame: up to 11 days after last dose of drug administration
measure: Number of subjects with abnormal changes in laboratory parameters
time frame: up to 11 days after last dose of drug administration
arm group label: TPV/r - Room condition
arm group type: Experimental
arm group label: TPV/r - Refrigerated conditions
arm group type: Experimental
intervention type: Drug
intervention name: TPV - Room condition
arm group label: TPV/r - Room condition
intervention type: Drug
intervention name: TPV - Refrigerated conditions
arm group label: TPV/r - Refrigerated conditions
intervention type: Drug
intervention name: Ritonavir (RTV)
arm group label: TPV/r - Refrigerated conditions
arm group label: TPV/r - Room condition
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