<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/NCT01689623</url>
  </required_header>
  <id_info>
    <org_study_id>CR100873</org_study_id>
    <secondary_id>TMC435HPC1006</secondary_id>
    <nct_id>NCT01689623</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic Interaction Study Between TMC435, Atorvastatin and Simvastatin in Healthy Participants</brief_title>
  <official_title>A Phase I, 2-Panel, Open-Label Study in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and the HMG-CoA Reductase Inhibitors Atorvastatin and Simvastatin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate effects of steady-state concentrations (constant&#xD;
      concentration of medication in the blood) of TMC435 on the single dose pharmacokinetics (what&#xD;
      the body does to the medication) of atorvastatin, the active metabolites ortho- and&#xD;
      parahydroxylated atorvastatin, simvastatin and the active metabolite simvastatin acid. Plasma&#xD;
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitory activity after a single&#xD;
      dose of atorvastatin or simvastatin, either alone or in combination with TMC435 will be also&#xD;
      evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I, 2-panel, open-label (all people know the identity of the intervention)&#xD;
      study in healthy participants to investigate the pharmacokinetic interaction between TMC435&#xD;
      and the HMG-CoA reductase inhibitors atorvastatin and simvastatin. The study consists of a&#xD;
      screening period (21 days prior to the first intake of study medication), a 17-day treatment&#xD;
      period and a 5-7 days follow-up period. Approximately thirty six healthy participants will be&#xD;
      equally divided to 2 panels (n=18 per panel). Within each panel all participants will receive&#xD;
      the same treatments in the same order. In Panel 1, each participant will be administered a&#xD;
      single oral 40-mg atorvastatin dose on Day 1 and Day 13. The participants will receive TMC435&#xD;
      at a dose of 150 mg once daily from Day 4 until Day 15. In Panel 2, each participant will be&#xD;
      administered a single oral 40-mg simvastatin dose on Day 1 and Day 13. TMC435 at a dose of&#xD;
      150 mg will be administered once daily from Day 4 until Day 15. Treatment duration (including&#xD;
      Day -1) will be 17 days for both panels (Panel 1 and Panel 2). Safety and tolerability will&#xD;
      be evaluated throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">August 2012</completion_date>
  <primary_completion_date type="Actual">August 2012</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of steady-state (constant concentration of medication in the blood) concentrations of TMC435 on the single dose pharmacokinetics (what the body does to the drug) of simvastatin and the active metabolite simvastatin acid</measure>
    <time_frame>Up to Day 16</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of steady-state concentrations of TMC435 on the single dose pharmacokinetics of atorvastatin and the active metabolites ortho- and parahydroxylated atorvastatin</measure>
    <time_frame>Up to Day 16</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitory activity after a single dose of atorvastatin or simvastatin, either alone or in combination with TMC435</measure>
    <time_frame>Up to Day 16</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the steady-state pharmacokinetics of TMC435 in the presence of atorvastatin or simvastatin</measure>
    <time_frame>Up to Day 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events as a measure of safety and tolerability</measure>
    <time_frame>Up to Day 24</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Healthy Participants</condition>
  <arm_group>
    <arm_group_label>Panel I</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will be administered a single oral 40-mg atorvastatin dose on Day 1 and Day 13. The participants will receive TMC435 once daily dose of 150 mg from Day 4 until Day 15.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel II</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each participant will be administered a single oral 40-mg simvastatin dose on Day 1 and Day 13. The participants will receive TMC435 once daily dose of 150 mg from Day 4 until Day 15.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TMC435</intervention_name>
    <description>Type=exact number, unit=mg, number=150, form=capsule, route=oral. TMC435 will be administered at a dose of 150 mg once daily from Day 4 until Day 15.</description>
    <arm_group_label>Panel I</arm_group_label>
    <arm_group_label>Panel II</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin</intervention_name>
    <description>Type=exact number, unit=mg, number=40, form=tablet, route=oral. Atorvastatin will be administered as a single oral 40-mg dose on Day 1 and Day 13.</description>
    <arm_group_label>Panel I</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Simvastatin</intervention_name>
    <description>Type=exact number, unit=mg, number=40, form=tablet, route=oral. Simvastatin will be administered as a single oral 40-mg on Day 1 and Day 13.</description>
    <arm_group_label>Panel II</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;
             clinical laboratory tests, and 12-lead electrocardiogram performed at screening&#xD;
&#xD;
          -  If a woman, before entry she must be postmenopausal for at least 2 years, as confirmed&#xD;
             by follicle stimulating hormone test, or surgically sterile (have had a total&#xD;
             hysterectomy or bilateral oophorectomy, tubal ligation/bilateral tubal clips), not&#xD;
             heterosexually active for the duration of the study, or if of childbearing potential&#xD;
             and heterosexually active, agree to use effective methods of birth control&#xD;
&#xD;
          -  If a man and heterosexually active with a woman of childbearing potential, he must&#xD;
             agree to use 2 effective methods of birth control and to not donate sperm during the&#xD;
             study and for 3 months after receiving the last dose of study drug&#xD;
&#xD;
          -  Have a Body Mass Index (weight in kg divided by the square of height in meters) of&#xD;
             18.0 to 30.0 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a history of liver or renal insufficiency; significant cardiac, vascular,&#xD;
             pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic,&#xD;
             psychiatric, neoplastic, or metabolic disturbances&#xD;
&#xD;
          -  Has a positive Human immunodeficiency virus (HIV)-1 or HIV-2 test at screening&#xD;
&#xD;
          -  Has a hepatitis A, B or C infection (confirmed by hepatitis A antibody immune globulin&#xD;
             M, hepatitis B surface antigen, or Hepatitis C virus (HCV) antibody, respectively) at&#xD;
             screening&#xD;
&#xD;
          -  Pregnant or breastfeeding woman&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2013</verification_date>
  <study_first_submitted>July 30, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>March 1, 2013</last_update_submitted>
  <last_update_submitted_qc>March 1, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 4, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy participants</keyword>
  <keyword>TMC435</keyword>
  <keyword>HMG-CoA reductase inhibitors</keyword>
  <keyword>Atorvastatin</keyword>
  <keyword>Simvastatin</keyword>
  <keyword>Pharmacokinetic interaction</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Simeprevir</mesh_term>
    <mesh_term>Atorvastatin</mesh_term>
    <mesh_term>Simvastatin</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/NCT01689623
org study id: CR100873
secondary id: TMC435HPC1006
nct id: NCT01689623
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate effects of steady-state concentrations (constant
      concentration of medication in the blood) of TMC435 on the single dose pharmacokinetics (what
      the body does to the medication) of atorvastatin, the active metabolites ortho- and
      parahydroxylated atorvastatin, simvastatin and the active metabolite simvastatin acid. Plasma
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitory activity after a single
      dose of atorvastatin or simvastatin, either alone or in combination with TMC435 will be also
      evaluated.
This is a Phase I, 2-panel, open-label (all people know the identity of the intervention)
      study in healthy participants to investigate the pharmacokinetic interaction between TMC435
      and the HMG-CoA reductase inhibitors atorvastatin and simvastatin. The study consists of a
      screening period (21 days prior to the first intake of study medication), a 17-day treatment
      period and a 5-7 days follow-up period. Approximately thirty six healthy participants will be
      equally divided to 2 panels (n=18 per panel). Within each panel all participants will receive
      the same treatments in the same order. In Panel 1, each participant will be administered a
      single oral 40-mg atorvastatin dose on Day 1 and Day 13. The participants will receive TMC435
      at a dose of 150 mg once daily from Day 4 until Day 15. In Panel 2, each participant will be
      administered a single oral 40-mg simvastatin dose on Day 1 and Day 13. TMC435 at a dose of
      150 mg will be administered once daily from Day 4 until Day 15. Treatment duration (including
      Day -1) will be 17 days for both panels (Panel 1 and Panel 2). Safety and tolerability will
      be evaluated throughout the study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Effect of steady-state (constant concentration of medication in the blood) concentrations of TMC435 on the single dose pharmacokinetics (what the body does to the drug) of simvastatin and the active metabolite simvastatin acid
time frame: Up to Day 16
measure: Effect of steady-state concentrations of TMC435 on the single dose pharmacokinetics of atorvastatin and the active metabolites ortho- and parahydroxylated atorvastatin
time frame: Up to Day 16
measure: Plasma hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitory activity after a single dose of atorvastatin or simvastatin, either alone or in combination with TMC435
time frame: Up to Day 16
measure: To evaluate the steady-state pharmacokinetics of TMC435 in the presence of atorvastatin or simvastatin
time frame: Up to Day 16
measure: Number of participants with adverse events as a measure of safety and tolerability
time frame: Up to Day 24
arm group label: Panel I
arm group type: Experimental
description: Each participant will be administered a single oral 40-mg atorvastatin dose on Day 1 and Day 13. The participants will receive TMC435 once daily dose of 150 mg from Day 4 until Day 15.
arm group label: Panel II
arm group type: Experimental
description: Each participant will be administered a single oral 40-mg simvastatin dose on Day 1 and Day 13. The participants will receive TMC435 once daily dose of 150 mg from Day 4 until Day 15.
intervention type: Drug
intervention name: TMC435
description: Type=exact number, unit=mg, number=150, form=capsule, route=oral. TMC435 will be administered at a dose of 150 mg once daily from Day 4 until Day 15.
arm group label: Panel I
arm group label: Panel II
intervention type: Drug
intervention name: Atorvastatin
description: Type=exact number, unit=mg, number=40, form=tablet, route=oral. Atorvastatin will be administered as a single oral 40-mg dose on Day 1 and Day 13.
arm group label: Panel I
intervention type: Drug
intervention name: Simvastatin
description: Type=exact number, unit=mg, number=40, form=tablet, route=oral. Simvastatin will be administered as a single oral 40-mg on Day 1 and Day 13.
arm group label: Panel II
criteria: 
gender: All
minimum age: 19 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Simeprevir
mesh term: Atorvastatin
mesh term: Simvastatin