<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/NCT02207790</url>
  </required_header>
  <id_info>
    <org_study_id>E2609-A001-006</org_study_id>
    <nct_id>NCT02207790</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2609 in Healthy Adult Male Japanese and White Subjects</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Single Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2609 in Healthy Adult Male Japanese and White Subjects</official_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>
      This study is primarily designed to bridge the pharmacokinetics (PK) and safety data for&#xD;
      E2609 between Japanese subjects and non-Japanese (ie, white) subjects. To bridge these PK&#xD;
      characteristics, the proposed study includes a cohort of white subjects treated for&#xD;
      comparison with the cohort of Japanese subjects treated at the same dose. This comparison&#xD;
      serves as a key PK bridge in assessing ethnic factors that may contribute to differences in&#xD;
      plasma concentrations. Pharmacokinetic assessments in the proposed study will include&#xD;
      confirmation of dose proportionality in Japanese subjects. This study will also evaluate&#xD;
      safety and tolerability in Japanese subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: Cmax</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: tmax</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: AUC(0-24h)+D90</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: AUC(0-72h)</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: AUC(0-t)</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: AUC(0-inf)</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: AUC Metabolite Ratio</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: t1/2</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: CL/F</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of E2609: V/F</measure>
    <time_frame>Up to Day 10 (216 hours postdose)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>To evaluate the safety and tolerability of E2609</measure>
    <time_frame>Baseline and up to 30 days from last dosing of subject</time_frame>
    <description>Safety will be assessed by monitoring and recording all adverse events (AEs), serious adverse events (SAEs), regular monitoring of hematology, blood chemistry, urine values, regular measurement of vital signs, ECGs and performance of physical examinations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Amax</measure>
    <time_frame>Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): T(Amax)</measure>
    <time_frame>Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(-24h-0h)</measure>
    <time_frame>Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(0-144h)</measure>
    <time_frame>Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Change in AUAC</measure>
    <time_frame>Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QTcF obtained from ECGs extracted from Holter recordings</measure>
    <time_frame>Baseline, Day 1, and Day 2</time_frame>
    <description>Holter ECG measurements will start on Day -1, at a time equivalent to 24 hours predose, and will continue for 24 hours postdose of Day 1, with interruptions allowed to adjust equipment. ECGs will be extracted from Holter monitors.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>E2609 low-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1 will consist of Japanese subjects randomized to a low-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>E2609 mid-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 2 will consist of Japanese subjects randomized to a mid-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>E2609 high-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 3 will consist of Japanese subjects randomized to a high-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>E2609 mid-dose and placebo in healthy White subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 4 will consist of White subjects randomized to a mid-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>E2609</intervention_name>
    <arm_group_label>E2609 high-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_label>E2609 low-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_label>E2609 mid-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_label>E2609 mid-dose and placebo in healthy White subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>E2609 low-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy Japanese subjects, E2609 high-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy White subjects</description>
    <arm_group_label>E2609 high-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_label>E2609 low-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_label>E2609 mid-dose and placebo in healthy Japanese subjects</arm_group_label>
    <arm_group_label>E2609 mid-dose and placebo in healthy White subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        The subject must meet all of the following criteria in order to be included in the study.&#xD;
&#xD;
        Japanese Subjects Only:&#xD;
&#xD;
          1. Birth in Japan to Japanese parents and grandparents of Japanese descent&#xD;
&#xD;
          2. Have been living outside Japan for less than 5 years&#xD;
&#xD;
          3. Lifestyle, including diet, has not changed significantly since leaving Japan&#xD;
&#xD;
             White Subjects Only:&#xD;
&#xD;
          4. A person having origins in any of the original peoples of Europe, the Middle East, or&#xD;
             North Africa based on documented subject self-report&#xD;
&#xD;
             All Subjects:&#xD;
&#xD;
          5. Healthy male, 30 to 60 years inclusive, at the time of informed consent&#xD;
&#xD;
          6. BMI of 18 to 32 kg/m2 inclusive at Screening&#xD;
&#xD;
          7. Subjects must have had a successful vasectomy (confirmed azoospermia) or they and&#xD;
             their female partners must not be of childbearing potential or must be practicing&#xD;
             highly effective contraception (i.e. condom plus spermicide, condom plus diaphragm&#xD;
             with spermicide, intrauterine device starting for at least one menstrual cycle before&#xD;
             starting study drug[s]) and throughout the study period and for 30 days after study&#xD;
             drug discontinuation. No sperm donation is allowed during the study period and for 30&#xD;
             days after study drug discontinuation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects who meet any of the following criteria will be excluded from this study:&#xD;
&#xD;
          1. Any history of seizures or epilepsy&#xD;
&#xD;
          2. Any medical condition which, in the opinion of the investigator has high risk of&#xD;
             seizures&#xD;
&#xD;
          3. Any history of cerebrovascular disease&#xD;
&#xD;
          4. A history of prolonged QTc interval&#xD;
&#xD;
          5. Any other clinically significant ECG abnormalities&#xD;
&#xD;
          6. History of risk factors for torsade de pointes or the use of medications that&#xD;
             prolonged the QT/QTc interval&#xD;
&#xD;
          7. Heart rate less than 50 or greater than 100 beats/min&#xD;
&#xD;
          8. History of ischemic heart disease&#xD;
&#xD;
          9. Persistent systolic blood pressure (BP) greater than 140 mmHg or less than 90 mmHg and&#xD;
             diastolic BP greater than 90 mmHg or less than 60 mmHg&#xD;
&#xD;
         10. Left bundle branch block&#xD;
&#xD;
         11. Evidence of clinically significant disease&#xD;
&#xD;
         12. Any laboratory abnormalities considered clinically significant&#xD;
&#xD;
         13. Clinically significant illness which requires medical treatment&#xD;
&#xD;
         14. Any history of abdominal surgery that may affect study drugs&#xD;
&#xD;
         15. Hypersensitivity to the study drug&#xD;
&#xD;
         16. Known to be HIV positive&#xD;
&#xD;
         17. Active viral hepatitis&#xD;
&#xD;
         18. History of drug or alcohol dependency or abuse within approximately the last 2 years&#xD;
&#xD;
         19. Scheduled for surgery during the study&#xD;
&#xD;
         20. Engagement in strenuous exercise within 2 weeks before dosing (eg, marathon runners,&#xD;
             weight lifters)&#xD;
&#xD;
         21. Currently enrolled in another clinical trial or used any investigational drug or&#xD;
             device within 30 days before informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>November 2, 2015</last_update_submitted>
  <last_update_submitted_qc>November 2, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Clinical Trial, Phase I</keyword>
  <keyword>Healthy Volunteers</keyword>
  <!-- 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/NCT02207790
org study id: E2609-A001-006
nct id: NCT02207790
lead sponsor: 
has dmc: No
This study is primarily designed to bridge the pharmacokinetics (PK) and safety data for
      E2609 between Japanese subjects and non-Japanese (ie, white) subjects. To bridge these PK
      characteristics, the proposed study includes a cohort of white subjects treated for
      comparison with the cohort of Japanese subjects treated at the same dose. This comparison
      serves as a key PK bridge in assessing ethnic factors that may contribute to differences in
      plasma concentrations. Pharmacokinetic assessments in the proposed study will include
      confirmation of dose proportionality in Japanese subjects. This study will also evaluate
      safety and tolerability in Japanese subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Pharmacokinetics of E2609: Cmax
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: tmax
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: AUC(0-24h)+D90
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: AUC(0-72h)
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: AUC(0-t)
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: AUC(0-inf)
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: AUC Metabolite Ratio
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: t1/2
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: CL/F
time frame: Up to Day 10 (216 hours postdose)
measure: Pharmacokinetics of E2609: V/F
time frame: Up to Day 10 (216 hours postdose)
measure: To evaluate the safety and tolerability of E2609
time frame: Baseline and up to 30 days from last dosing of subject
description: Safety will be assessed by monitoring and recording all adverse events (AEs), serious adverse events (SAEs), regular monitoring of hematology, blood chemistry, urine values, regular measurement of vital signs, ECGs and performance of physical examinations
measure: Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Amax
time frame: Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10
measure: Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): T(Amax)
time frame: Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10
measure: Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(-24h-0h)
time frame: Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10
measure: Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(0-144h)
time frame: Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10
measure: Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Change in AUAC
time frame: Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10
measure: Change from baseline in QTcF obtained from ECGs extracted from Holter recordings
time frame: Baseline, Day 1, and Day 2
description: Holter ECG measurements will start on Day -1, at a time equivalent to 24 hours predose, and will continue for 24 hours postdose of Day 1, with interruptions allowed to adjust equipment. ECGs will be extracted from Holter monitors.
arm group label: E2609 low-dose and placebo in healthy Japanese subjects
arm group type: Experimental
description: Cohort 1 will consist of Japanese subjects randomized to a low-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).
arm group label: E2609 mid-dose and placebo in healthy Japanese subjects
arm group type: Experimental
description: Cohort 2 will consist of Japanese subjects randomized to a mid-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).
arm group label: E2609 high-dose and placebo in healthy Japanese subjects
arm group type: Experimental
description: Cohort 3 will consist of Japanese subjects randomized to a high-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).
arm group label: E2609 mid-dose and placebo in healthy White subjects
arm group type: Experimental
description: Cohort 4 will consist of White subjects randomized to a mid-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).
intervention type: Drug
intervention name: E2609
arm group label: E2609 high-dose and placebo in healthy Japanese subjects
arm group label: E2609 low-dose and placebo in healthy Japanese subjects
arm group label: E2609 mid-dose and placebo in healthy Japanese subjects
arm group label: E2609 mid-dose and placebo in healthy White subjects
intervention type: Drug
intervention name: Placebo
description: E2609 low-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy Japanese subjects, E2609 high-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy White subjects
arm group label: E2609 high-dose and placebo in healthy Japanese subjects
arm group label: E2609 low-dose and placebo in healthy Japanese subjects
arm group label: E2609 mid-dose and placebo in healthy Japanese subjects
arm group label: E2609 mid-dose and placebo in healthy White subjects
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor