<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/NCT02198170</url>
  </required_header>
  <id_info>
    <org_study_id>E7080-A001-004</org_study_id>
    <nct_id>NCT02198170</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic Study to Assess the Influence of Simultaneous CYP3A4 and P-glycoprotein Inhibition on E7080 Pharmacokinetics Following Single Dose Oral Administration of 5 mg E7080 to Healthy Volunteers</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eisai Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the influence of simultaneous CYP3A4 and&#xD;
      p-glycoprotein inhibition on lenvatinib pharmacokinetics following a single oral dose of 5 mg&#xD;
      lenvatinib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, randomized, open-label, two-period, crossover study consisting of&#xD;
      two phases: Prerandomization and Randomization. The Prerandomization Phase will have two&#xD;
      periods: Screening and Baseline 1. The Randomization Phase will have two periods: Treatment&#xD;
      Period 1 and Treatment Period 2 with a Baseline 2 assessment prior to Treatment Period 2. In&#xD;
      the Randomization Phase, subjects will be randomized to one of two possible treatment&#xD;
      sequences (placebo/ketoconazole or ketoconazole/placebo). Ketoconazole 400 mg or placebo will&#xD;
      be orally administered once daily for the first four days of each treatment period. On the&#xD;
      fifth day of each treatment period, in addition to ketoconazole/placebo, 5 mg lenvatinib will&#xD;
      be orally administered. Ketoconazole/placebo administration will then continue for 13&#xD;
      additional days. Subjects are crossed over from Treatment Period 1 to Treatment Period 2&#xD;
      after a 2-week washout.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2011</start_date>
  <completion_date type="Actual">June 2011</completion_date>
  <primary_completion_date type="Actual">June 2011</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: Cmax</measure>
    <time_frame>Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-t)</measure>
    <time_frame>Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-inf)</measure>
    <time_frame>Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety as Measured by Outcome of Adverse Events</measure>
    <time_frame>Screening, Up to Day 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety as Measured by Laboratory Values</measure>
    <time_frame>Screening, Up to Day 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety as Measured by Vital Signs</measure>
    <time_frame>Screening, Up to Day 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety as Measured by ECGs</measure>
    <time_frame>Screening, Up to Day 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety as Measured by Physical Examination</measure>
    <time_frame>Screening, Up to Day 52</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>ketoconazole-placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo-ketoconazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ketoconazole-placebo</intervention_name>
    <description>Treatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period. Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period.</description>
    <arm_group_label>ketoconazole-placebo</arm_group_label>
    <other_name>E7080</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo-ketoconazole</intervention_name>
    <description>Treatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period</description>
    <arm_group_label>placebo-ketoconazole</arm_group_label>
    <other_name>E7080</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Non-smoking (i.e., no use of nicotine or nicotine containing products within the past&#xD;
             3 months), male or female subjects, age greater than or equal to 18 years and less&#xD;
             than or equal to 55 years&#xD;
&#xD;
          2. Body mass index (BMI) greater than or equal to 18 and less than or equal to 30 kg/m2&#xD;
             at screening&#xD;
&#xD;
          3. All females must have a negative serum and urine B-hCG test result at Screening and&#xD;
             Baseline. Females of child-bearing potential must agree to use a medically acceptable&#xD;
             method of contraception (e.g., abstinence; a highly effective method such as an&#xD;
             intrauterine device [IUD], condom + spermicide or condom + diaphragm with spermicide,&#xD;
             a contraceptive implant, an oral contraceptive; or have a vasectomized partner)&#xD;
             throughout the entire study period and for 30 days after study drug discontinuation.&#xD;
             The only subjects who will be exempt from this requirement are postmenopausal women&#xD;
             (defined as greater than age 50 and at least 12 months of amenorrhea) or subjects who&#xD;
             have been sterilized surgically or who are otherwise proven sterile (e.g., bilateral&#xD;
             tubal ligation with surgery at least 6 months prior to dosing, hysterectomy, or&#xD;
             bilateral oophorectomy with surgery at least 2 months prior to dosing). All women who&#xD;
             are of reproductive potential and who are using hormonal contraceptives must have been&#xD;
             on a stable dose of the same hormonal contraceptive product for at least 12 weeks&#xD;
             prior to dosing and must continue to use the same contraceptive during the study and&#xD;
             for 30 days after study drug discontinuation.&#xD;
&#xD;
          4. Male subjects who are not abstinent or have undergone a successful vasectomy, who are&#xD;
             partners of women of childbearing potential must use, or their partners must use a&#xD;
             highly effective method of contraception (e.g., condom + spermicide, condom +&#xD;
             diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to&#xD;
             starting study drug(s) and throughout the entire study and for 30 days after the last&#xD;
             dose of study drug. Those with partners using hormonal contraceptives must also be&#xD;
             using an additional approved method of contraception (as described previously).&#xD;
&#xD;
          5. Provide written informed consent&#xD;
&#xD;
          6. Are willing and able to comply with all aspects of the protocol&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Subjects who had a clinically significant illness that required medical treatment&#xD;
             within 8 weeks or a clinically significant infection within 4 weeks of dosing&#xD;
&#xD;
          2. Subjects with a disease that may influence the outcome of the study; such as&#xD;
             psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney,&#xD;
             respiratory system, endocrine system, hematological system, neurological system, or&#xD;
             cardiovascular system, or subjects who have a congenital abnormality in metabolism&#xD;
             within 4 weeks prior to dosing&#xD;
&#xD;
          3. Subjects with a history of gastrointestinal surgery (hepatectomy, nephrotomy,&#xD;
             digestive organ resection, etc.) that may affect pharmacokinetic profiles of&#xD;
             lenvatinib&#xD;
&#xD;
          4. Subjects with a known history of clinically significant drug or food allergies or&#xD;
             presently experiencing significant seasonal allergy&#xD;
&#xD;
          5. Subjects who experienced a weight loss or gain of greater than 10% between screening&#xD;
             and prior to dosing&#xD;
&#xD;
          6. Subjects with any clinically abnormal symptom or organ impairment found on medical&#xD;
             history, symptoms/signs, vital signs, ECG finding, or laboratory test results which&#xD;
             require medical treatment&#xD;
&#xD;
          7. Subjects with a QTc interval greater than 450 ms at screening or check-in&#xD;
&#xD;
          8. Subjects with hemoglobin level less than 12.0 g/dL&#xD;
&#xD;
          9. Subjects who had a positive result from human immunodeficiency virus (HIV) or&#xD;
             hepatitis C virus antibody (HCVAb) screening tests, or clinical evidence of active&#xD;
             viral Hepatitis A or B&#xD;
&#xD;
         10. Subjects with a known or suspected history of drug or alcohol misuse within 6 months&#xD;
             prior to screening, or a positive urine drug or alcohol test at screening or baseline&#xD;
&#xD;
         11. Subjects who have consumed caffeinated beverages within 72 hours prior to baseline&#xD;
&#xD;
         12. Subjects who have taken dietary supplements, juice, or herbal preparations or other&#xD;
             foods or beverages that may affect various drug metabolizing enzymes and transporters&#xD;
             [e.g., alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple&#xD;
             or orange juice), vegetables from the mustard green family (e.g., kale, broccoli,&#xD;
             watercress, collard greens, kohlrabi, brussel sprouts, mustard), and charbroiled&#xD;
             meats] within 2 weeks prior to dosing&#xD;
&#xD;
         13. Subjects who have taken herbal preparations containing St. John's Wort within 4 weeks&#xD;
             prior to dosing&#xD;
&#xD;
         14. Subjects who have taken prescription drugs within 4 weeks prior to screening (however,&#xD;
             use of prescription contraceptive products is permitted)&#xD;
&#xD;
         15. Subjects who have taken over-the-counter (OTC) medications within 2 weeks prior to&#xD;
             dosing&#xD;
&#xD;
         16. Subjects who have participated in another clinical trial of an investigational drug or&#xD;
             device within 4 weeks prior to dosing&#xD;
&#xD;
         17. Subjects who have received blood products within 4 weeks, or donated blood within 8&#xD;
             weeks, or donated plasma within 1 week of dosing&#xD;
&#xD;
         18. Subjects who have engaged in heavy exercise within 2 weeks prior to check-in (e.g.,&#xD;
             marathon runners, weight lifters, etc.)&#xD;
&#xD;
         19. Subjects who are unwilling or unable to abide by the requirements of the study&#xD;
&#xD;
         20. Subjects who have any condition that would make him/her, in the opinion of the&#xD;
             investigator, unsuitable for the study or who, in the opinion of the investigator, are&#xD;
             not likely to complete the study for any reason&#xD;
&#xD;
         21. Known intolerance to the study drugs or any of the excipients&#xD;
&#xD;
         22. Females who are either pregnant or lactating&#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>
  <location>
    <facility>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98418</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>February 11, 2015</last_update_submitted>
  <last_update_submitted_qc>February 11, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 13, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy Volunteers</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketoconazole</mesh_term>
    <mesh_term>Lenvatinib</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/NCT02198170
org study id: E7080-A001-004
nct id: NCT02198170
lead sponsor: 
has dmc: No
The purpose of this study is to assess the influence of simultaneous CYP3A4 and
      p-glycoprotein inhibition on lenvatinib pharmacokinetics following a single oral dose of 5 mg
      lenvatinib.
This is a single-center, randomized, open-label, two-period, crossover study consisting of
      two phases: Prerandomization and Randomization. The Prerandomization Phase will have two
      periods: Screening and Baseline 1. The Randomization Phase will have two periods: Treatment
      Period 1 and Treatment Period 2 with a Baseline 2 assessment prior to Treatment Period 2. In
      the Randomization Phase, subjects will be randomized to one of two possible treatment
      sequences (placebo/ketoconazole or ketoconazole/placebo). Ketoconazole 400 mg or placebo will
      be orally administered once daily for the first four days of each treatment period. On the
      fifth day of each treatment period, in addition to ketoconazole/placebo, 5 mg lenvatinib will
      be orally administered. Ketoconazole/placebo administration will then continue for 13
      additional days. Subjects are crossed over from Treatment Period 1 to Treatment Period 2
      after a 2-week washout.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: Cmax
time frame: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
measure: Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-t)
time frame: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
measure: Pharmacokinetics of CYP3A4 and p-glycoprotein inhibition on lenvatinib: AUC(0-inf)
time frame: Baseline 1 (Day -1) and 2 (Day 33); Treatment period 1 and 2: Predose and at 0.5, 1, 2, 3, 4, 8, 12, 16, 24, 48, 72, 96, 120, 144, 168, 240, 288, and 336 hours post dose
measure: Safety as Measured by Outcome of Adverse Events
time frame: Screening, Up to Day 52
measure: Safety as Measured by Laboratory Values
time frame: Screening, Up to Day 52
measure: Safety as Measured by Vital Signs
time frame: Screening, Up to Day 52
measure: Safety as Measured by ECGs
time frame: Screening, Up to Day 52
measure: Safety as Measured by Physical Examination
time frame: Screening, Up to Day 52
arm group label: ketoconazole-placebo
arm group type: Experimental
description: Treatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period
arm group label: placebo-ketoconazole
arm group type: Experimental
description: Treatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period
intervention type: Drug
intervention name: ketoconazole-placebo
description: Treatment Period 1: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period. Treatment Period 2: Placebo orally once daily + single oral dose of 5 mg lenvatinib of fifth day on 19-day treatment period.
arm group label: ketoconazole-placebo
other name: E7080
intervention type: Drug
intervention name: placebo-ketoconazole
description: Treatment Period 1: Placebo orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period Treatment Period 2: 400 mg ketoconazole orally once daily + single oral dose of 5 mg lenvatinib on fifth day of 19-day treatment period
arm group label: placebo-ketoconazole
other name: E7080
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ketoconazole
mesh term: Lenvatinib