<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/NCT02244190</url>
  </required_header>
  <id_info>
    <org_study_id>1182.124</org_study_id>
    <nct_id>NCT02244190</nct_id>
  </id_info>
  <brief_title>Bioequivalence of Two Different Oral Solutions Tipranavir Administered in Combination With Ritonavir to Healthy Volunteers</brief_title>
  <official_title>Bioequivalence of Two Different Oral Solutions of 500 mg of Tipranavir (New Formulation vs. Current Formulation) Administered in Combination With 200 mg of Ritonavir (Oral Solution) to Healthy Volunteers (an Open-label, Randomised, Single Dose, Two-way Crossover Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To establish the bioequivalence of the new tipranavir oral solution formulation with the&#xD;
      current tipranavir oral solution formulation following single-dose administration. In each&#xD;
      case, 500 mg tipranavir was coadministered with 200 mg ritonavir.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2008</start_date>
  <primary_completion_date type="Actual">May 2008</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 drug in plasma over the time interval from 0 extrapolated to infinity) for tipranavir</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax (maximum measured concentration of drug in plasma) for tipranavir</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ for ritonavir</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax for ritonavir</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of drug in plasma over the time interval from 0 to the time of the last quantifiable data point)</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 drug in plasma)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant of drug 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 drug in plasma)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo (mean residence time of drug in the body after oral administration)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLpo/F (apparent clearance of drug after oral 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 following an extravascular dose)</measure>
    <time_frame>up to 72 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 43 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant findings in vital signs</measure>
    <time_frame>up to 43 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant findings in 12-lead electrocardiogram</measure>
    <time_frame>up to 43 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant findings in laboratory tests</measure>
    <time_frame>up to 43 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>Day 4 of each treatment period</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>new Tipranavir + Ritonavir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>current Tipranavir + Ritonavir</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <description>New oral solution (back up) formulation</description>
    <arm_group_label>new Tipranavir + Ritonavir</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <arm_group_label>current Tipranavir + Ritonavir</arm_group_label>
    <other_name>Current oral solution formulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>current Tipranavir + Ritonavir</arm_group_label>
    <arm_group_label>new Tipranavir + Ritonavir</arm_group_label>
    <other_name>Norvir®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males and females according to the following criteria based upon a complete&#xD;
             medical history, including the physical examination, vital signs (BP, PR), 12-lead&#xD;
             ECG, clinical laboratory tests&#xD;
&#xD;
          -  Age ≥ 18 and ≤ 55 years&#xD;
&#xD;
          -  BMI ≥ 18.5 and ≤ 29.9 kg/m2 (Body Mass Index) and body weight &gt; 55 kg&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including BP, PR and ECG) deviating from&#xD;
             normal and of clinical relevance&#xD;
&#xD;
          -  Any evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Surgery of the gastrointestinal tract (except appendectomy)&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  History of relevant orthostatic hypotension, fainting spells or blackouts.&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of relevant allergy/hypersensitivity (including allergy to tipranavir or&#xD;
             ritonavir or their excipients)&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24 hours) within at least one month or less&#xD;
             than 10 half-lives of the respective drug prior to administration of the trial drug or&#xD;
             during the trial&#xD;
&#xD;
          -  Cytochrome P 450 (CYP3A4)-inhibiting drugs (e.g. itraconazole, ketoconazole, protease&#xD;
             inhibitors, erythromycin, clarithromycin, telithromycin, nefazodone, cyclosporin,&#xD;
             verapamil, amiodarone, diltiazem), CYP3A4 inducing drugs (e.g. St. John´s wort&#xD;
             [Hypericum perforatum], rifampin, dexamethasone) or CYP3A4 substrates (e.g. triazolam,&#xD;
             sertraline); further drugs which might reasonably influence the results of the trial&#xD;
             (e.g. drugs which contain polyethylene glycol) or drugs that prolong the QT/corrected&#xD;
             QT interval interval (based on the knowledge at the time of protocol preparation)&#xD;
             within 14 days prior to first administration of the trial drug or during the trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within two months prior to&#xD;
             administration of the trial drug or during the trial&#xD;
&#xD;
          -  Smoker (&gt; 10 cigarettes or &gt; 3 cigars or &gt; 3 pipes/day)&#xD;
&#xD;
          -  Inability to refrain from smoking within 24 hours before or after administration of&#xD;
             the trial drug&#xD;
&#xD;
          -  Alcohol abuse (more than 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL within four weeks prior to administration of the&#xD;
             trial drug or during the trial)&#xD;
&#xD;
          -  Excessive physical activities (within one week prior to administration of the trial&#xD;
             drug or during the trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range that is of clinical relevance&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a&#xD;
             QTc interval &gt;450 ms)&#xD;
&#xD;
          -  A history of additional risk factors for Torsades de Pointes (TdP), e.g., heart&#xD;
             failure, hypokalaemia, family history of Long QT Syndrome&#xD;
&#xD;
          -  Known hypersensitivity to antiretroviral drugs (marketed or experimental use as part&#xD;
             of clinical research studies)&#xD;
&#xD;
          -  Personal or family history of coagulation or bleeding disorders or bleeding tendencies&#xD;
&#xD;
          -  Intake of vitamin E within 14 days prior to the first drug administration of this&#xD;
             trial or during the trial&#xD;
&#xD;
          -  Transaminase values (ALT /AST) greater than the upper limit of the normal laboratory&#xD;
             reference range during screening&#xD;
&#xD;
        For female subjects:&#xD;
&#xD;
          -  Pregnancy or positive pregnancy test, or planning to become pregnant during the study&#xD;
             or within 1 month of study completion&#xD;
&#xD;
          -  No adequate contraception during the study and until 1 month of study completion, i.e.&#xD;
             not any of the following: implants, injectables, combined oral contraceptives,&#xD;
             intrauterine device, sexual abstinence (for at least 1 month prior to enrolment),&#xD;
             vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or&#xD;
             surgical sterilisation (incl. hysterectomy). Females who do not have a vasectomised&#xD;
             partner, are not sexually abstinent or surgically sterile will be asked to&#xD;
             additionally use barrier contraception methods (e.g. condom, diaphragm with&#xD;
             spermicide).&#xD;
&#xD;
          -  Lactation period&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 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>
  </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/NCT02244190
org study id: 1182.124
nct id: NCT02244190
lead sponsor: 
To establish the bioequivalence of the new tipranavir oral solution formulation with the
      current tipranavir oral solution formulation following single-dose administration. In each
      case, 500 mg tipranavir was coadministered with 200 mg ritonavir.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-∞ (area under the concentration-time curve of drug in plasma over the time interval from 0 extrapolated to infinity) for tipranavir
time frame: up to 72 hours after drug administration
measure: Cmax (maximum measured concentration of drug in plasma) for tipranavir
time frame: up to 72 hours after drug administration
measure: AUC0-∞ for ritonavir
time frame: up to 72 hours after drug administration
measure: Cmax for ritonavir
time frame: up to 72 hours after drug administration
measure: AUC0-tz (area under the concentration-time curve of drug in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to 72 hours after drug administration
measure: tmax (time from dosing to the maximum concentration of drug in plasma)
time frame: up to 72 hours after drug administration
measure: λz (terminal rate constant of drug in plasma)
time frame: up to 72 hours after drug administration
measure: t1/2 (terminal half-life of drug in plasma)
time frame: up to 72 hours after drug administration
measure: MRTpo (mean residence time of drug in the body after oral administration)
time frame: up to 72 hours after drug administration
measure: CLpo/F (apparent clearance of drug after oral administration)
time frame: up to 72 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
time frame: up to 72 hours after drug administration
measure: Number of patients with adverse events
time frame: up to 43 days
measure: Number of patients with clinically significant findings in vital signs
time frame: up to 43 days
measure: Number of patients with clinically significant findings in 12-lead electrocardiogram
time frame: up to 43 days
measure: Number of patients with clinically significant findings in laboratory tests
time frame: up to 43 days
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: Day 4 of each treatment period
arm group label: new Tipranavir + Ritonavir
arm group type: Experimental
arm group label: current Tipranavir + Ritonavir
arm group type: Active Comparator
intervention type: Drug
intervention name: Tipranavir
description: New oral solution (back up) formulation
arm group label: new Tipranavir + Ritonavir
intervention type: Drug
intervention name: Tipranavir
arm group label: current Tipranavir + Ritonavir
other name: Current oral solution formulation
intervention type: Drug
intervention name: Ritonavir
arm group label: current Tipranavir + Ritonavir
arm group label: new Tipranavir + Ritonavir
other name: Norvir®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 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