<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/NCT01719614</url>
  </required_header>
  <id_info>
    <org_study_id>CR100909</org_study_id>
    <secondary_id>TMC278IFD1004</secondary_id>
    <nct_id>NCT01719614</nct_id>
  </id_info>
  <brief_title>A Study to Explore Pharmacokinetic Interaction Between Rilpivirine and Metformin in Healthy Participants</brief_title>
  <official_title>A Phase I, Open-Label Study in Healthy Subjects to Explore the Potential for a Pharmacokinetic Interaction Between Steady-State Rilpivirine and a Single Dose Of Metformin</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 the study is to evaluate the effect of steady-state (constant concentration of&#xD;
      medication in the blood) rilpivirine on pharmacokinetics (how a single dose of metformin is&#xD;
      absorbed in the body, distributed within the body, and removed from the body) of a single&#xD;
      dose of metformin, over time, in healthy adult participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase I, open-label (all people know the identity of the intervention) and&#xD;
      sequential study (study medication is given in a sequence) in healthy participants, to&#xD;
      investigate the pharmacokinetic interaction between steady-state rilpivirine and a single&#xD;
      dose of metformin. The study consists of 3 phases including, the screening phase (28 days&#xD;
      before enrollment), treatment phase (19 days), and the follow-up phase (7 days after the last&#xD;
      intake of study medication). All participants will receive study medications in two sessions&#xD;
      in a fixed, sequential order as a session 1 (a single dose of metformin on Day 1) followed by&#xD;
      washout period (period when no treatment is received) of 4 days and then session 2&#xD;
      (rilpivirine on Day 5 to Day 17 with a single dose of metformin on Day 15). The duration of&#xD;
      the study is approximately 54 days. Safety evaluations including adverse events, clinical&#xD;
      laboratory tests, electrocardiogram, vital signs, and physical examination (including skin&#xD;
      examination) will be monitored throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">January 2013</completion_date>
  <primary_completion_date type="Actual">January 2013</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>Maximum observed plasma analyte concentration (Cmax) of metformin</measure>
    <time_frame>Day 1 and Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Actual sampling time to reach the maximum plasma analyte concentration (tmax) of metformin</measure>
    <time_frame>Day 1 and Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under curve from time of administration up to the last time point with a measurable plasma analyte concentration after dosing (AUClast) of metformin</measure>
    <time_frame>Day 1 and Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC extrapolated to infinity of metformin</measure>
    <time_frame>Day 1 and Day 15</time_frame>
    <description>AUC extrapolated to infinity, calculated as AUClast + Clast/apparent terminal elimination rate constant, where Clast is the last measurable plasma analyte concentration; extrapolations of more than 20 percent of the total AUC are reported as approximations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent terminal elimination rate constant of metformin</measure>
    <time_frame>Day 1 and Day 15</time_frame>
    <description>Apparent terminal elimination rate constant will be estimated by linear regression using the terminal log-linear phase of the logarithmic transformed conentration versus time data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent terminal elimination half-life of metformin</measure>
    <time_frame>Day 1 and Day 15</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Predose plasma analyte concentration (C0h) of rilpivirine</measure>
    <time_frame>Day 12, Day 13, Day 14, Day 15, Day 17, Day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum observed plasma analyte concentration (Cmin) of rilpivirine</measure>
    <time_frame>Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma analyte concentration (Cmax) of rilpivirine</measure>
    <time_frame>Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Actual sampling time to reach the maximum plasma analyte concentration (tmax) of rilpivirine</measure>
    <time_frame>Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed plasma analyte concentration at the end of the 24-hour dosing interval (C24h)</measure>
    <time_frame>Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC from time of administration up to 24 hours after administration (AUC24h)</measure>
    <time_frame>Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average steady-state plasma concentration (Css,av)</measure>
    <time_frame>Day 15</time_frame>
    <description>Css,av is calculated by AUC dosing interval/dosing interval at steady-state</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluctuation index (FI)</measure>
    <time_frame>Day 15</time_frame>
    <description>FI, percentage fluctuation is variation between maximum and minimum plasma concentration at steady-state</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events as a measure of safety and tolerability</measure>
    <time_frame>Up to 54 Days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Healthy Participants</condition>
  <arm_group>
    <arm_group_label>Rilpivirine+Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will receive study medications in two sessions in a fixed, sequential order as a session 1 (a single dose of metformin on Day 1) followed by washout period (period when no treatment is received) of 4 days and then session 2 (rilpivirine on Day 5 to Day 17 with a single dose of metformin on Day 15).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Type=exact number, unit=mg, number=850, form=tablet, route=oral. Participants will receive single dose of metformin on Day 1 and Day 15.</description>
    <arm_group_label>Rilpivirine+Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rilpivirine</intervention_name>
    <description>Type=exact number, unit=mg, number=25, form=tablet route=oral. Participants will receive 1 tablet of rilpivirine from Day 5 to Day 17.</description>
    <arm_group_label>Rilpivirine+Metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants should be healthy on the basis of physical examination, medical history,&#xD;
             vital signs, electrocardiogram, the results of blood biochemistry and hematology tests&#xD;
             and a urinalysis performed at screening&#xD;
&#xD;
          -  Participant must have a Body Mass Index of 18.5 to 30.0 kg/m2&#xD;
&#xD;
          -  Male participants should agree to protocol-defined use of effective contraception and&#xD;
             women must be postmenopausal or surgically sterile&#xD;
&#xD;
          -  Female participants must have a negative pregnancy test at screening&#xD;
&#xD;
          -  Participants must be non-smoking for at least 3 months prior to screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A positive Human immunodeficiency virus (HIV)-1 or HIV-2 test and Hepatitis A, B or C&#xD;
             infection at screening&#xD;
&#xD;
          -  Currently active clinically significant gastrointestinal, cardiovascular, neurologic,&#xD;
             psychiatric, metabolic, endocrine, renal, hepatic, respiratory, inflammatory or&#xD;
             infectious disease with any history of clinically significant skin disease&#xD;
&#xD;
          -  Any history of tuberculosis, ocular herpes, or uveitis&#xD;
&#xD;
          -  Have previously participated in more than one study with etravirine - TMC120&#xD;
             (dapivirine) and/or rilpivirine&#xD;
&#xD;
          -  Participants with abnormal laboratory values at screening&#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>
  <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>Overland Park</city>
        <state>Kansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2014</verification_date>
  <study_first_submitted>October 30, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <last_update_submitted>March 5, 2014</last_update_submitted>
  <last_update_submitted_qc>March 5, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 6, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy participants</keyword>
  <keyword>Rilpivirine</keyword>
  <keyword>Metformin</keyword>
  <keyword>Pharmacokinetics</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Rilpivirine</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/NCT01719614
org study id: CR100909
secondary id: TMC278IFD1004
nct id: NCT01719614
lead sponsor: 
has dmc: No
The purpose of the study is to evaluate the effect of steady-state (constant concentration of
      medication in the blood) rilpivirine on pharmacokinetics (how a single dose of metformin is
      absorbed in the body, distributed within the body, and removed from the body) of a single
      dose of metformin, over time, in healthy adult participants.
This is a phase I, open-label (all people know the identity of the intervention) and
      sequential study (study medication is given in a sequence) in healthy participants, to
      investigate the pharmacokinetic interaction between steady-state rilpivirine and a single
      dose of metformin. The study consists of 3 phases including, the screening phase (28 days
      before enrollment), treatment phase (19 days), and the follow-up phase (7 days after the last
      intake of study medication). All participants will receive study medications in two sessions
      in a fixed, sequential order as a session 1 (a single dose of metformin on Day 1) followed by
      washout period (period when no treatment is received) of 4 days and then session 2
      (rilpivirine on Day 5 to Day 17 with a single dose of metformin on Day 15). The duration of
      the study is approximately 54 days. Safety evaluations including adverse events, clinical
      laboratory tests, electrocardiogram, vital signs, and physical examination (including skin
      examination) will be monitored throughout the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum observed plasma analyte concentration (Cmax) of metformin
time frame: Day 1 and Day 15
measure: Actual sampling time to reach the maximum plasma analyte concentration (tmax) of metformin
time frame: Day 1 and Day 15
measure: Area under curve from time of administration up to the last time point with a measurable plasma analyte concentration after dosing (AUClast) of metformin
time frame: Day 1 and Day 15
measure: AUC extrapolated to infinity of metformin
time frame: Day 1 and Day 15
description: AUC extrapolated to infinity, calculated as AUClast + Clast/apparent terminal elimination rate constant, where Clast is the last measurable plasma analyte concentration; extrapolations of more than 20 percent of the total AUC are reported as approximations.
measure: Apparent terminal elimination rate constant of metformin
time frame: Day 1 and Day 15
description: Apparent terminal elimination rate constant will be estimated by linear regression using the terminal log-linear phase of the logarithmic transformed conentration versus time data.
measure: Apparent terminal elimination half-life of metformin
time frame: Day 1 and Day 15
measure: Predose plasma analyte concentration (C0h) of rilpivirine
time frame: Day 12, Day 13, Day 14, Day 15, Day 17, Day 18
measure: Minimum observed plasma analyte concentration (Cmin) of rilpivirine
time frame: Day 15
measure: Maximum observed plasma analyte concentration (Cmax) of rilpivirine
time frame: Day 15
measure: Actual sampling time to reach the maximum plasma analyte concentration (tmax) of rilpivirine
time frame: Day 15
measure: Observed plasma analyte concentration at the end of the 24-hour dosing interval (C24h)
time frame: Day 15
measure: AUC from time of administration up to 24 hours after administration (AUC24h)
time frame: Day 15
measure: Average steady-state plasma concentration (Css,av)
time frame: Day 15
description: Css,av is calculated by AUC dosing interval/dosing interval at steady-state
measure: Fluctuation index (FI)
time frame: Day 15
description: FI, percentage fluctuation is variation between maximum and minimum plasma concentration at steady-state
measure: Number of participants with adverse events as a measure of safety and tolerability
time frame: Up to 54 Days
arm group label: Rilpivirine+Metformin
arm group type: Experimental
description: All participants will receive study medications in two sessions in a fixed, sequential order as a session 1 (a single dose of metformin on Day 1) followed by washout period (period when no treatment is received) of 4 days and then session 2 (rilpivirine on Day 5 to Day 17 with a single dose of metformin on Day 15).
intervention type: Drug
intervention name: Metformin
description: Type=exact number, unit=mg, number=850, form=tablet, route=oral. Participants will receive single dose of metformin on Day 1 and Day 15.
arm group label: Rilpivirine+Metformin
intervention type: Drug
intervention name: Rilpivirine
description: Type=exact number, unit=mg, number=25, form=tablet route=oral. Participants will receive 1 tablet of rilpivirine from Day 5 to Day 17.
arm group label: Rilpivirine+Metformin
criteria: 
gender: All
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: United States
responsible party type: Sponsor
mesh term: Metformin
mesh term: Rilpivirine