<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/NCT03768609</url>
  </required_header>
  <id_info>
    <org_study_id>CR108557</org_study_id>
    <secondary_id>2018-002819-10</secondary_id>
    <secondary_id>63623872FLZ1015</secondary_id>
    <nct_id>NCT03768609</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Effect of Cyclosporine, a P-Glycoprotein, Breast Cancer Resistance Protein, and Organic-Anion-Transporting Polypeptide Inhibitor, on Pimodivir in Healthy Adults</brief_title>
  <official_title>A Randomized, Open-label, Single-dose, 2-period, 2-sequence, Crossover, Phase 1 Study to Evaluate the Effect of Cyclosporine, a P-glycoprotein, Breast Cancer Resistance Protein, and Organic-anion-transporting Polypeptide Inhibitor, on the Pharmacokinetics of Pimodivir in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen-Cilag International NV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen-Cilag International NV</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effect of a single oral dose of cyclosporine on&#xD;
      the pharmacokinetics of a single oral dose of pimodivir when coadministered to healthy adult&#xD;
      participants under fasted conditions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2018</start_date>
  <completion_date type="Actual">March 12, 2019</completion_date>
  <primary_completion_date type="Actual">March 6, 2019</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8</time_frame>
    <description>Cmax is defined as maximum observed plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration Time (AUC [0-Last])</measure>
    <time_frame>Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8</time_frame>
    <description>AUC(0-Last) is area under the plasma concentration-time curve from time zero to time of the last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])</measure>
    <time_frame>Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8</time_frame>
    <description>AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); where C(last) is the last observed measurable (non-below quantification limit) concentration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability</measure>
    <time_frame>Approximately 65 days</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Group 1: Sequence AB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Treatment A (pimodivir 600 milligram [mg] orally as two tablets of 300 mg each) on Day 1 in Period 1 followed by Treatment B (pimodivir 600 mg as two tablets of 300 mg each plus cyclosporine 400 mg orally as four capsules of 100 mg each) on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: Sequence BA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive Treatment B on Day 1 in Period 1 followed by Treatment A on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimodivir</intervention_name>
    <description>Participants will be administered pimodivir 600 mg orally as two tablets of 300 mg each.</description>
    <arm_group_label>Group 1: Sequence AB</arm_group_label>
    <arm_group_label>Group 2: Sequence BA</arm_group_label>
    <other_name>JNJ-63623872</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclosporine</intervention_name>
    <description>Participants will be administered cyclosporine 400 mg orally as 4 capsules of 100 mg each.</description>
    <arm_group_label>Group 1: Sequence AB</arm_group_label>
    <arm_group_label>Group 2: Sequence BA</arm_group_label>
    <other_name>NEORAL</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to adhere to the prohibitions and restrictions specified in this&#xD;
             protocol&#xD;
&#xD;
          -  A woman of childbearing potential must have a negative highly sensitive serum&#xD;
             (beta-human chorionic gonadotropin [beta-hCG]) at screening and on Day -1 of each&#xD;
             treatment period&#xD;
&#xD;
          -  A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted&#xD;
             reproduction during the study and for a period of at least 30 days after the last&#xD;
             study drug intake&#xD;
&#xD;
          -  A male participant must wear a condom when engaging in any activity that allows for&#xD;
             passage of ejaculate to another person (male participants should also be advised of&#xD;
             the benefit for a female partner to use a highly effective method of contraception as&#xD;
             condom may break or leak)&#xD;
&#xD;
          -  A male participant must agree not to donate sperm for the purpose of reproduction&#xD;
             during the study and for a minimum of 90 days after last study drug intake&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of or current clinically significant medical illness including (but not&#xD;
             limited to) cardiac arrhythmias or other cardiac disease, hematologic disease,&#xD;
             coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid&#xD;
             abnormalities, significant pulmonary disease, including bronchospastic respiratory&#xD;
             disease, diabetes mellitus, hepatic or renal insufficiency (creatinine clearance below&#xD;
             90 milliliter per minute at screening), gastrointestinal disease (such as significant&#xD;
             diarrhea, gastric stasis, or constipation that in the investigator's opinion could&#xD;
             influence drug absorption or bioavailability), thyroid disease, neurologic or&#xD;
             psychiatric disease, infection, or any other illness that the investigator considers&#xD;
             should exclude the participant or that could interfere with the interpretation of the&#xD;
             study results&#xD;
&#xD;
          -  History of clinically significant skin disease such as, but not limited to,&#xD;
             dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria&#xD;
&#xD;
          -  Known allergies, hypersensitivity, or intolerance to pimodivir and/or cyclosporine or&#xD;
             their excipients&#xD;
&#xD;
          -  History of clinically significant drug allergy such as, but not limited to,&#xD;
             sulfonamides and penicillins, or drug allergy diagnosed in previous studies with&#xD;
             experimental drugs&#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-Cilag International NV Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen-Cilag International NV</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Pharmacology Unit</name>
      <address>
        <city>Merksem</city>
        <zip>2170</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>April 26, 2019</last_update_submitted>
  <last_update_submitted_qc>April 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 29, 2019</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>Cyclosporine</mesh_term>
    <mesh_term>Cyclosporins</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data sharing policy of the Janssen Pharmaceutical Companies of Johnson &amp; Johnson is available at www.janssen.com/clinical-trials\transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu</ipd_description>
    <ipd_url>https://www.janssen.com/clinical-trials/transparency</ipd_url>
  </patient_data>
  <!-- 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/NCT03768609
org study id: CR108557
secondary id: 2018-002819-10
secondary id: 63623872FLZ1015
nct id: NCT03768609
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the effect of a single oral dose of cyclosporine on
      the pharmacokinetics of a single oral dose of pimodivir when coadministered to healthy adult
      participants under fasted conditions.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Maximum Observed Plasma Concentration (Cmax)
time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8
description: Cmax is defined as maximum observed plasma concentration.
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration Time (AUC [0-Last])
time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8
description: AUC(0-Last) is area under the plasma concentration-time curve from time zero to time of the last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 5, 6 , 8, 12, 16, 24, 48, 72, 96, 120, 144, 168 hours postdose on Day 8
description: AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); where C(last) is the last observed measurable (non-below quantification limit) concentration.
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
time frame: Approximately 65 days
description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment.
arm group label: Group 1: Sequence AB
arm group type: Experimental
description: Participants will receive Treatment A (pimodivir 600 milligram [mg] orally as two tablets of 300 mg each) on Day 1 in Period 1 followed by Treatment B (pimodivir 600 mg as two tablets of 300 mg each plus cyclosporine 400 mg orally as four capsules of 100 mg each) on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.
arm group label: Group 2: Sequence BA
arm group type: Experimental
description: Participants will receive Treatment B on Day 1 in Period 1 followed by Treatment A on Day 1 in Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 14 days.
intervention type: Drug
intervention name: Pimodivir
description: Participants will be administered pimodivir 600 mg orally as two tablets of 300 mg each.
arm group label: Group 1: Sequence AB
arm group label: Group 2: Sequence BA
other name: JNJ-63623872
intervention type: Drug
intervention name: Cyclosporine
description: Participants will be administered cyclosporine 400 mg orally as 4 capsules of 100 mg each.
arm group label: Group 1: Sequence AB
arm group label: Group 2: Sequence BA
other name: NEORAL
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen-Cilag International NV Clinical Trial
role: Study Director
affiliation: Janssen-Cilag International NV
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Cyclosporine
mesh term: Cyclosporins
sharing ipd: Yes
ipd description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials\transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu
ipd url: https://www.janssen.com/clinical-trials/transparency