<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/NCT02245451</url>
  </required_header>
  <id_info>
    <org_study_id>1182.26</org_study_id>
    <nct_id>NCT02245451</nct_id>
  </id_info>
  <brief_title>Study of Tipranavir and Ritonavir on the Pharmacokinetic Characteristics of Methadone Administered in Healthy Volunteers</brief_title>
  <official_title>A Single-centre, Open-label Study of Multiple Doses of Tipranavir 500 mg and Ritonavir 200 mg (Twice Daily) on the Pharmacokinetic Characteristics of Methadone Administered as a Single Dose 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>
      The primary objective of this study is to characterise the effects of tipranavir 500 mg and&#xD;
      ritonavir 200 mg (TPV/r; given twice daily) at steady-state on the pharmacokinetics of&#xD;
      methadone administered as a single dose in healthy adult volunteers&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2005</start_date>
  <primary_completion_date type="Actual">February 2005</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</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 concentration-time curve for 0 to 24 hours (AUC0-24h) of methadone</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum concentration (Cmax)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentration at 6 hours (C6h) of methadone</measure>
    <time_frame>6 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve for 0 to 12 hours (AUC0-12h) of tipranavir and ritonavir</measure>
    <time_frame>up to 12 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>concentration at 12 hours (C12h) of tipranavir and ritonavir</measure>
    <time_frame>12 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>mean residence time (MRT)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>apparent terminal half-life (t½)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to maximum concentration (Tmax)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>oral clearance (CL/F)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>apparent volume of distribution during the terminal elimination phase divided by the bioavailability factor (Vz/F)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with abnormal findings in physical examination</measure>
    <time_frame>Up to day 17 after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant changes in vital signs</measure>
    <time_frame>Up to day 17 after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with abnormal changes in clinical laboratory parameters</measure>
    <time_frame>Up to day 17 after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>Up to day 17 after first drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>TPV/r with methadone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tipranavir</intervention_name>
    <arm_group_label>TPV/r with methadone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <arm_group_label>TPV/r with methadone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methadone</intervention_name>
    <arm_group_label>TPV/r with methadone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female healthy volunteers aged at least 18 to 60 years.&#xD;
&#xD;
          -  Clinically normal medical history.&#xD;
&#xD;
          -  Clinically normal findings on physical examination.&#xD;
&#xD;
          -  Clinically normal laboratory values.&#xD;
&#xD;
          -  A Body Mass Index &gt;18.5 and &lt;30 kg/m2.&#xD;
&#xD;
          -  Able to swallow large capsules without difficulty.&#xD;
&#xD;
          -  Capable of comprehending and communicating effectively with the investigator and staff&#xD;
             and of providing written informed consent in accordance with ethics committee and&#xD;
             regulatory guidelines.&#xD;
&#xD;
          -  Willing to stay in the study centre for the duration of the study.&#xD;
&#xD;
          -  Willing to abstain from ingesting substances during the study which may alter plasma&#xD;
             study drug levels by interaction with the cytochrome P450 system.&#xD;
&#xD;
          -  Willing to abstain from alcohol for 48 hours prior to Visit 1 and for the duration of&#xD;
             the study. In addition, Cabernet Sauvignon must not have been ingested within 15 days&#xD;
             prior to Visit 1.&#xD;
&#xD;
          -  Willing to abstain from ingesting grapefruit and grapefruit juice for 15 days before&#xD;
             Visit 1 and for the duration of the study.&#xD;
&#xD;
          -  Willing to abstain from ingesting Seville oranges, strawberries or strawberry extract,&#xD;
             garlic supplements, St. John's Wort, Milk Thistle, or methylxanthine-containing drinks&#xD;
             or food (coffee, tea, cola, energy drinks, chocolate, etc) for 72 hours before the&#xD;
             pharmacokinetic sampling days.&#xD;
&#xD;
          -  Willing to abstain from use of tobacco products for the duration of the study.&#xD;
&#xD;
          -  Urine drug screen negative for illegal non-prescription drugs.&#xD;
&#xD;
          -  Negative HIV serology.&#xD;
&#xD;
          -  Negative for Hepatitis B surface antigen and Hepatitis C&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any clinically significant disease. (A significant disease was defined as a disease&#xD;
             which in the opinion of the investigator may either have put the subject at risk&#xD;
             because of participation in the study or a disease which may have influenced the&#xD;
             results of the study or the subject's ability to participate in the study.)&#xD;
&#xD;
          -  Clinically significant abnormal baseline haematology, blood chemistry or urinalysis&#xD;
             findings.&#xD;
&#xD;
          -  Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol,&#xD;
             triglyceride or glucose greater than the upper limit of normal at Visit 1.&#xD;
&#xD;
          -  Treatment with prohibited medications in the thirty days before the study or during&#xD;
             the study or ingestion of drugs of abuse.&#xD;
&#xD;
          -  Treatment with any investigational drug within 90 days of the first dose of study&#xD;
             medication.&#xD;
&#xD;
          -  Inability to adhere to the requirements of the protocol (including active substance&#xD;
             abuse) as assessed by the investigator.&#xD;
&#xD;
          -  Prior tipranavir use.&#xD;
&#xD;
          -  Ingestion of any known enzyme altering drug (such as phenothiazines, cimetidine,&#xD;
             barbiturates, ketoconazole, fluconazole, clarithromycin, rifampin, steroids, and&#xD;
             herbal medications) for thirty days prior to Visit 1.&#xD;
&#xD;
          -  Ingestion of grapefruit, grapefruit juice, and Cabernet Sauvignon within fifteen days&#xD;
             prior to Visit 1.&#xD;
&#xD;
          -  Ingestion of Seville oranges, strawberries or strawberry extract, garlic supplements,&#xD;
             St. John's Wort, Milk Thistle, or methylxanthine-containing drinks or food (coffee,&#xD;
             tea, cola, energy drinks, chocolate, etc) within 72 hours of pharmacokinetics sampling&#xD;
             days.&#xD;
&#xD;
          -  Treatment with prescription medicines within thirty days prior to Visit 1.&#xD;
&#xD;
          -  History of gastrointestinal, hepatic, or renal disorders within 60 days prior to Visit&#xD;
             1.&#xD;
&#xD;
          -  Any history of alcohol or drug abuse.&#xD;
&#xD;
          -  Current use of cigarettes defined as greater than 10 cigarettes per day or&#xD;
             rolling/pipe tobacco equivalent.&#xD;
&#xD;
          -  Blood or plasma donations within 90 days prior to Visit 1&#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;100 beats/min.&#xD;
&#xD;
          -  Subjects with a history of any illness or allergy that, in the opinion of the&#xD;
             investigator, might have confounded the results of the study or posed additional risk&#xD;
             in administering tipranavir, ritonavir or methadone to the subject.&#xD;
&#xD;
          -  Subjects who had an acute illness within two weeks prior to Visit 1.&#xD;
&#xD;
          -  Subjects who were currently taking any over-the-counter drug within fourteen days&#xD;
             prior to Visit 1 or who were currently taking any prescription drug.&#xD;
&#xD;
          -  Hypersensitivity to tipranavir, ritonavir, or methadone.&#xD;
&#xD;
          -  Female subjects who are of reproductive potential and who were pregnant,&#xD;
             breastfeeding, had a positive serum B-HCG at Visit 1 or 2, had not been using a&#xD;
             barrier contraceptive method for at least three months prior to Study Day 1 or were&#xD;
             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 the&#xD;
             study and for thirty days after completion or termination of 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</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>Methadone</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/NCT02245451
org study id: 1182.26
nct id: NCT02245451
lead sponsor: 
The primary objective of this study is to characterise the effects of tipranavir 500 mg and
      ritonavir 200 mg (TPV/r; given twice daily) at steady-state on the pharmacokinetics of
      methadone administered as a single dose in healthy adult volunteers
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the concentration-time curve for 0 to 24 hours (AUC0-24h) of methadone
time frame: up to 24 hours after drug administration
measure: Maximum concentration (Cmax)
time frame: up to 24 hours after drug administration
measure: Concentration at 6 hours (C6h) of methadone
time frame: 6 hours after drug administration
measure: Area under the concentration-time curve for 0 to 12 hours (AUC0-12h) of tipranavir and ritonavir
time frame: up to 12 hours after drug administration
measure: concentration at 12 hours (C12h) of tipranavir and ritonavir
time frame: 12 hours after drug administration
measure: mean residence time (MRT)
time frame: up to 24 hours after drug administration
measure: apparent terminal half-life (t½)
time frame: up to 24 hours after drug administration
measure: time to maximum concentration (Tmax)
time frame: up to 24 hours after drug administration
measure: oral clearance (CL/F)
time frame: up to 24 hours after drug administration
measure: apparent volume of distribution during the terminal elimination phase divided by the bioavailability factor (Vz/F)
time frame: up to 24 hours after drug administration
measure: Number of patients with abnormal findings in physical examination
time frame: Up to day 17 after first drug administration
measure: Number of patients with clinically significant changes in vital signs
time frame: Up to day 17 after first drug administration
measure: Number of patients with abnormal changes in clinical laboratory parameters
time frame: Up to day 17 after first drug administration
measure: Number of participants with adverse events
time frame: Up to day 17 after first drug administration
arm group label: TPV/r with methadone
arm group type: Experimental
intervention type: Drug
intervention name: Tipranavir
arm group label: TPV/r with methadone
intervention type: Drug
intervention name: Ritonavir
arm group label: TPV/r with methadone
intervention type: Drug
intervention name: Methadone
arm group label: TPV/r with methadone
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
mesh term: Tipranavir
mesh term: Methadone