<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/NCT01707342</url>
  </required_header>
  <id_info>
    <org_study_id>CR100901</org_study_id>
    <secondary_id>TMC435-TiDP16-C118</secondary_id>
    <secondary_id>2012-002330-37</secondary_id>
    <nct_id>NCT01707342</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Absolute Bioavailability and Pharmacokinetics of Simeprevir (TMC435) Administered as Single Oral Doses of TMC435 and an Intravenous Microdose of [3H]-TMC435 in Healthy Male Patients</brief_title>
  <official_title>A Phase I, Open-Label, Sequential, Single-Dose Study to Assess the Absolute Bioavailability and Pharmacokinetics of TMC435 Administered as Single Oral Doses of 50 mg and 150 mg and an Intravenous Microdose of 100 μg [3H]-TMC435 in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen R&amp;D Ireland</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen R&amp;D Ireland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the absolute bioavailability and pharmacokinetics&#xD;
      (what the body does to the medication) of simeprevir (TMC435) after administration of single&#xD;
      oral doses of 50 mg and 150 mg when administered together with a single intravenous (IV) dose&#xD;
      of 100 microgram [3H]-TMC435 in healthy male participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label (all people know the identity of the intervention), sequential (a&#xD;
      single group of participants where study medication is administered in a sequence),&#xD;
      single-dose study to assess the absolute bioavailability and pharmacokinetics (what the body&#xD;
      does to the medication) of single oral doses of 50 mg and 150 mg simeprevir (TMC435)&#xD;
      administered together with an intravenous (IV) microdose of 100 microgram [3H]-TMC435 in&#xD;
      healthy male participants. The study consists of 3 phases, screening phase (21 days prior to&#xD;
      administration of study medication), treatment phase, and a follow up phase. In the treatment&#xD;
      phase, participants will receive 2 treatments, ie, Treatment A: single oral dose of&#xD;
      simeprevir (TMC435) 50 mg followed 5 hours later by a single 10 minute IV infusion of&#xD;
      [3H]-TMC435 (100 microcurie) 100 microgram; and Treatment B: single oral dose of simeprevir&#xD;
      (TMC435) 150 mg followed 5 hours later by a single 10 minute IV infusion of [3H]-TMC435 (100&#xD;
      microcurie) 100 microgram. Treatments will be administered in two consecutive treatment&#xD;
      periods, first Treatment A in Period 1, followed by Treatment B in Period 2; separated by a&#xD;
      washout period (period when the participant is not receiving any study medication) of 7 to 14&#xD;
      days. The follow up will be for 5 to 7 days after end of Period 2. Blood samples will be&#xD;
      collected for full plasma pharmacokinetics evaluations; along with urine and stool samples&#xD;
      for analysis of total plasma radioactivity. Safety evaluations for adverse events, clinical&#xD;
      laboratory tests, electrocardiogram, vital signs, physical examination, liver volume&#xD;
      determination, and specific toxicities will be monitored throughout the study. The total&#xD;
      duration of the study will be approximately 42 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2012</completion_date>
  <primary_completion_date type="Actual">November 2012</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>Absolute bioavailability of simeprevir (TMC435)</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Volume of distribution of [3H]-TMC435 and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed plasma concentration of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to reach the maximum observed plasma concentration of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration versus time curve from time of administration up to the last time point with a measurable concentration post dosing of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration versus time curve extrapolated to infinity of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the first moment of the concentration versus time curve from the time of dosing up to a definite time, to infinity, or to the time of the last measureable concentration of [3H]-TMC435 and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean residence time of [3H]-TMC435 and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal elimination rate constant of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal elimination half-life of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total systemic clearance of drug following single-dose intravenous administration of [3H]-TMC435 and [3H]-total radioactivity</measure>
    <time_frame>Pre-dose Day 1, post-dose Days 1-4</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total radioactivity excreted into the feces from time 0 to the time of discharge</measure>
    <time_frame>Post-dose Hours 5, 24, 48, 72, and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total radioactivity excreted into the feces expressed as a percentage of the administered dose</measure>
    <time_frame>Post-dose Hours 5, 24, 48, 72, and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total radioactivity excreted into urine from time 0 to the time of discharge</measure>
    <time_frame>Post-dose Hours 5, 24, 48, 72, and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total radioactivity excreted into the urine expressed as a percentage of the administered dose</measure>
    <time_frame>Post-dose Hours 5, 24, 48, 72, and 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>up to 30 days after dose of study medications</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Healthy Male Participants</condition>
  <arm_group>
    <arm_group_label>Simeprevir (TMC435)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment A: single oral dose of simeprevir (TMC435) 50 mg; and Treatment B: single oral dose of simeprevir (TMC435) 150 mg. A single 10 minute intravenous infusion of [3H]-TMC435 (100 microcurie) 100 microgram will be followed 5 hours later after administration of Treatment A and Treatment B in Period 1 and Period 2, respectively.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Simeprevir (TMC435)</intervention_name>
    <description>Treatment A: Simeprevir (TMC435) 50 mg; and Treatment B: Simeprevir (TMC435) 150 mg; will be followed 5 hours later by a single 10 minute intravenous infusion of [3H]-TMC435 (100 microcurie) 100 microgram in Period 1 and Period 2, respectively.</description>
    <arm_group_label>Simeprevir (TMC435)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be healthy on the basis of physical examination, medical history, vital signs,&#xD;
             12-lead electrocardiogram, and clinical laboratory tests performed at screening&#xD;
&#xD;
          -  Must be non-smoking for at least 3 months prior to screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of liver or renal insufficiency&#xD;
&#xD;
          -  Have any ferromagnetic medical implants or medical devices that can be de-programmed&#xD;
             by strong magnetic fields such as, but not limited to: cardiac pacemakers, implantable&#xD;
             cardiac defibrillators, cochlear implants, or insulin pumps&#xD;
&#xD;
          -  Had a surgical intervention on brain or eyes or has an intraocular foreign metallic&#xD;
             object&#xD;
&#xD;
          -  Has a history of anxiety and claustrophobia&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen R&amp;D Ireland Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen R&amp;D Ireland</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Merksem</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>March 2014</verification_date>
  <study_first_submitted>October 12, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <last_update_submitted>March 27, 2014</last_update_submitted>
  <last_update_submitted_qc>March 27, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 28, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy male participants</keyword>
  <keyword>Absolute bioavailability</keyword>
  <keyword>Bioavailability</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Simeprevir</keyword>
  <keyword>TMC435</keyword>
  <keyword>[3H]-TMC435</keyword>
  <keyword>Hepatitis C virus</keyword>
  <keyword>HCV</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Simeprevir</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/NCT01707342
org study id: CR100901
secondary id: TMC435-TiDP16-C118
secondary id: 2012-002330-37
nct id: NCT01707342
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the absolute bioavailability and pharmacokinetics
      (what the body does to the medication) of simeprevir (TMC435) after administration of single
      oral doses of 50 mg and 150 mg when administered together with a single intravenous (IV) dose
      of 100 microgram [3H]-TMC435 in healthy male participants.
This is an open-label (all people know the identity of the intervention), sequential (a
      single group of participants where study medication is administered in a sequence),
      single-dose study to assess the absolute bioavailability and pharmacokinetics (what the body
      does to the medication) of single oral doses of 50 mg and 150 mg simeprevir (TMC435)
      administered together with an intravenous (IV) microdose of 100 microgram [3H]-TMC435 in
      healthy male participants. The study consists of 3 phases, screening phase (21 days prior to
      administration of study medication), treatment phase, and a follow up phase. In the treatment
      phase, participants will receive 2 treatments, ie, Treatment A: single oral dose of
      simeprevir (TMC435) 50 mg followed 5 hours later by a single 10 minute IV infusion of
      [3H]-TMC435 (100 microcurie) 100 microgram; and Treatment B: single oral dose of simeprevir
      (TMC435) 150 mg followed 5 hours later by a single 10 minute IV infusion of [3H]-TMC435 (100
      microcurie) 100 microgram. Treatments will be administered in two consecutive treatment
      periods, first Treatment A in Period 1, followed by Treatment B in Period 2; separated by a
      washout period (period when the participant is not receiving any study medication) of 7 to 14
      days. The follow up will be for 5 to 7 days after end of Period 2. Blood samples will be
      collected for full plasma pharmacokinetics evaluations; along with urine and stool samples
      for analysis of total plasma radioactivity. Safety evaluations for adverse events, clinical
      laboratory tests, electrocardiogram, vital signs, physical examination, liver volume
      determination, and specific toxicities will be monitored throughout the study. The total
      duration of the study will be approximately 42 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Absolute bioavailability of simeprevir (TMC435)
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Volume of distribution of [3H]-TMC435 and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Maximum observed plasma concentration of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Time to reach the maximum observed plasma concentration of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Area under the concentration versus time curve from time of administration up to the last time point with a measurable concentration post dosing of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Area under the concentration versus time curve extrapolated to infinity of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Area under the first moment of the concentration versus time curve from the time of dosing up to a definite time, to infinity, or to the time of the last measureable concentration of [3H]-TMC435 and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Mean residence time of [3H]-TMC435 and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Terminal elimination rate constant of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Terminal elimination half-life of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Total systemic clearance of drug following single-dose intravenous administration of [3H]-TMC435 and [3H]-total radioactivity
time frame: Pre-dose Day 1, post-dose Days 1-4
measure: Total radioactivity excreted into the feces from time 0 to the time of discharge
time frame: Post-dose Hours 5, 24, 48, 72, and 96
measure: Total radioactivity excreted into the feces expressed as a percentage of the administered dose
time frame: Post-dose Hours 5, 24, 48, 72, and 96
measure: Total radioactivity excreted into urine from time 0 to the time of discharge
time frame: Post-dose Hours 5, 24, 48, 72, and 96
measure: Total radioactivity excreted into the urine expressed as a percentage of the administered dose
time frame: Post-dose Hours 5, 24, 48, 72, and 96
measure: Number of participants with adverse events
time frame: up to 30 days after dose of study medications
arm group label: Simeprevir (TMC435)
arm group type: Experimental
description: Treatment A: single oral dose of simeprevir (TMC435) 50 mg; and Treatment B: single oral dose of simeprevir (TMC435) 150 mg. A single 10 minute intravenous infusion of [3H]-TMC435 (100 microcurie) 100 microgram will be followed 5 hours later after administration of Treatment A and Treatment B in Period 1 and Period 2, respectively.
intervention type: Drug
intervention name: Simeprevir (TMC435)
description: Treatment A: Simeprevir (TMC435) 50 mg; and Treatment B: Simeprevir (TMC435) 150 mg; will be followed 5 hours later by a single 10 minute intravenous infusion of [3H]-TMC435 (100 microcurie) 100 microgram in Period 1 and Period 2, respectively.
arm group label: Simeprevir (TMC435)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen R&D Ireland Clinical Trial
role: Study Director
affiliation: Janssen R&D Ireland
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Simeprevir