<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/NCT02222324</url>
  </required_header>
  <id_info>
    <org_study_id>E2609-A001-004</org_study_id>
    <nct_id>NCT02222324</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Effects of E2609 on QTc Interval in Healthy Subjects</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo and Active-Controlled, Single-Dose, 4-Treatment Crossover Study to Evaluate the Effects of E2609 on QTc Interval in Healthy 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 thorough QT (TQT) study will take place in healthy subjects administered single doses of&#xD;
      study drug. It will be a randomized, double-blind, placebo and active-controlled, 4-treatment&#xD;
      crossover study. Subjects will be randomized in an equal ratio to one of 12 possible&#xD;
      treatment sequences. Each treatment sequence will comprise all 4 treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will consist of 2 phases: Prerandomization and Randomization. The Prerandomization&#xD;
      Phase will have 2 periods: Screening (up to 27 days) and Baseline Period 1 (1 day).&#xD;
      Eligibility will be determined during the Screening Period. The Randomization Phase will&#xD;
      consist of 8 periods: Treatment Period 1, Baseline Period 2, Treatment Period 2, Baseline&#xD;
      Period 3, Treatment Period 3, Baseline Period 4, Treatment Period 4, and a Follow-Up Period.&#xD;
      Each Baseline Period will last 1 day, followed by the corresponding treatment period. On the&#xD;
      first day of each treatment period, subjects will receive a single dose of the assigned study&#xD;
      drug. During each treatment period, subjects will be required to stay in the clinical unit&#xD;
      from the baseline period to 24 hours postdose. Subjects will then be released from the clinic&#xD;
      and will undergo a washout interval of at least 13 days, during which time they will return&#xD;
      for additional PK sampling.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">October 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in QTcF obtained from ECGs extracted from the Holter recordings</measure>
    <time_frame>Up to 24 hours postdose during each treatment period</time_frame>
    <description>Holter recordings are taken from a portable device for continuously monitoring various electrical activity of the cardiovascular system for at least 24 hours. Baseline is defined as the mean of predose QTcF values obtained from ECGs extracted from Holter recordings before dosing during each treatment period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ECG recordings: PR interval</measure>
    <time_frame>Predose and then up to 24 hours postdose in each treatment period</time_frame>
    <description>Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ECG recordings: QRS interval</measure>
    <time_frame>Predose and then up to 24 hours postdose in each treatment period</time_frame>
    <description>Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ECG recordings: HR</measure>
    <time_frame>Predose and then up 24 hours postdose in each treatment period</time_frame>
    <description>Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ECG recordings: RR interval</measure>
    <time_frame>Predose and then at up to 24 hours postdose in each treatment period</time_frame>
    <description>Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in ECG recordings: T wave morphology</measure>
    <time_frame>Predose and then at up to 24 hours postdose in each treatment period</time_frame>
    <description>Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of E2609: Cmax</measure>
    <time_frame>Up to 84 Days</time_frame>
    <description>Maximum drug concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of E2609: tmax</measure>
    <time_frame>Up to 84 Days</time_frame>
    <description>Ttime to reach maximum (peak) concentration following drug administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of E2609: AUC(0-t)</measure>
    <time_frame>Up to 84 Days</time_frame>
    <description>Area under the concentration x time curve from time = 0 to time of last measurable concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of E2609: AUC(0-72h)</measure>
    <time_frame>Up to 84 Days</time_frame>
    <description>Area under the concentration x time curve from time = 0 to 72 hours postdose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of E2609: AUC(0-inf)</measure>
    <time_frame>Up to 84 Days</time_frame>
    <description>Area under the concentration x time curve from time = 0 to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of E2609: t1/2</measure>
    <time_frame>Up to 84 Days</time_frame>
    <description>Terminal elimination half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of E2609: CL/F</measure>
    <time_frame>Up to 84 Days</time_frame>
    <description>Apparent total clearance following extravascular administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of E2609: Vz/F</measure>
    <time_frame>Up to 84 Days</time_frame>
    <description>Apparent volume of distribution following extravascular administration</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>E2609 Low dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>E2609 High dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Moxifloxacin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>8 placebo tablets matching E2609</description>
    <arm_group_label>Treatment A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>E2609</intervention_name>
    <description>E2609 will be administered as 8 tablets</description>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_label>Treatment C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Moxifloxacin</intervention_name>
    <description>Administered as 1 tablet with 7 tablets of placebo matching E2609</description>
    <arm_group_label>Treatment D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Subjects must meet all of the following criteria to be included in this study:&#xD;
&#xD;
          1. Healthy, non-smoking, male or female subjects ages greater than or equal to 18 years&#xD;
             to less than or equal to 55 years old at the time of informed consent&#xD;
&#xD;
          2. Body mass index (BMI) of greater than or equal to 18 to less than or equal to 30 kg/m2&#xD;
             at Screening&#xD;
&#xD;
          3. Females must not be lactating or pregnant at Screening or Baseline (as documented by a&#xD;
             negative betahuman chorionic gonadotropin [B-hCG]). A separate baseline assessment is&#xD;
             required if a negative screening pregnancy test was obtained more than 72 hours before&#xD;
             the first dose of study drug.&#xD;
&#xD;
          4. Females of childbearing potential must not have had unprotected sexual intercourse&#xD;
             within 30 days before study entry and must agree to use a highly effective method of&#xD;
             contraception (eg, total abstinence, an intrauterine device, a double-barrier method&#xD;
             [such as condom plus diaphragm with spermicide], or have a vasectomized partner with&#xD;
             confirmed azoospermia, but not oral contraceptive or contraceptive implant) throughout&#xD;
             the entire study period and for 30 days after study drug discontinuation. If currently&#xD;
             abstinent, the subject must agree to use a double barrier method as described above if&#xD;
             she becomes sexually active during the study period or for 30 days after study drug&#xD;
             discontinuation. Hormonal contraceptives (oral or implant) are not permitted forms of&#xD;
             contraception in this study. All females will be considered to be of childbearing&#xD;
             potential unless they are postmenopausal (amenorrheic for at least 12 consecutive&#xD;
             months, in the appropriate age group and without other known or suspected cause) or&#xD;
             have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or&#xD;
             bilateral oophorectomy, all with surgery at least one month before dosing).&#xD;
&#xD;
          5. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and&#xD;
             their female partners must meet the criteria above (ie, not of childbearing potential&#xD;
             or practicing highly effective contraception throughout the study period and for 30&#xD;
             days after study drug discontinuation). No sperm donation is allowed during the study&#xD;
             period and for 90 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. Clinically significant illness that requires medical treatment within 8 weeks or a&#xD;
             clinically significant infection that requires medical treatment within 4 weeks before&#xD;
             dosing&#xD;
&#xD;
          2. Evidence of disease that may influence the outcome of the study within 4 weeks before&#xD;
             dosing (eg, psychiatric disorders and disorders of the gastrointestinal tract, liver,&#xD;
             kidney, respiratory system, endocrine system, hematological system, neurological&#xD;
             system, or cardiovascular system, or subjects who have a congenital abnormality in&#xD;
             metabolism)&#xD;
&#xD;
          3. Any history of gastrointestinal surgery that may affect PK profiles of study drugs&#xD;
             (eg, hepatectomy, nephrectomy, or digestive organ resection)&#xD;
&#xD;
          4. Any clinically abnormal symptom or organ impairment found by medical history, physical&#xD;
             examinations, vital signs, ECG finding, or laboratory test results that requires&#xD;
             medical treatment at Screening or Baseline Periods&#xD;
&#xD;
          5. History of any medical condition which, in the opinion of the investigator, may&#xD;
             interfere with study procedures or compromise subject safety&#xD;
&#xD;
          6. A prolonged QT/corrected QT interval (QTc) interval (QTc greater than 450 msec) as&#xD;
             demonstrated by the mean of triplicate ECGs at Screening or Baseline Periods&#xD;
&#xD;
          7. History of risk factors for torsade de pointes or the use of concomitant medications&#xD;
             that prolonged the QT/QTc interval&#xD;
&#xD;
          8. Persistent systolic blood pressure (BP) greater than 130 mmHg or less than 90 mmHg and&#xD;
             diastolic BP greater than 85 mmHg or less than 60 mmHg at Screening or Baseline&#xD;
             Periods&#xD;
&#xD;
          9. Heart rate less than 50 or greater than 100 beats/minute at Screening or Baseline&#xD;
             Periods&#xD;
&#xD;
         10. History of prolonged QT/QTc interval&#xD;
&#xD;
         11. Left bundle branch block at Screening or Baseline Periods&#xD;
&#xD;
         12. History of myocardial infarction or active ischemic heart disease&#xD;
&#xD;
         13. History of clinically significant arrhythmia or uncontrolled arrhythmia&#xD;
&#xD;
         14. Any other clinically significant ECG abnormalities at Screening or Baseline Periods&#xD;
&#xD;
         15. Known history of clinically significant drug allergy (including to study drugs or any&#xD;
             of their excipients) at Screening or Baseline&#xD;
&#xD;
         16. Known history of food allergies or presently experiencing significant seasonal or&#xD;
             perennial allergy at Screening or Baseline Periods&#xD;
&#xD;
         17. Active viral hepatitis (B or C) as demonstrated by positive serology at Screening&#xD;
&#xD;
         18. History of drug or alcohol dependency or abuse within the 2 years before Screening, or&#xD;
             who have a positive urine drug or alcohol test at Screening or Baseline Periods&#xD;
&#xD;
         19. Use of recreational drugs&#xD;
&#xD;
         20. Intake of caffeinated beverages or food within 72 hours before dosing&#xD;
&#xD;
         21. Intake of nutritional supplements, juice, and herbal preparations or other foods or&#xD;
             beverages that may affect the various drug metabolizing enzymes and transporters (eg,&#xD;
             alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or&#xD;
             orange juice, vegetables from the mustard green family [eg, kale, broccoli,&#xD;
             watercress, collard greens, kohlrabi, brussel sprouts, mustard], and charbroiled&#xD;
             meats) within 1 week before dosing&#xD;
&#xD;
         22. Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing&#xD;
&#xD;
         23. Use of prescription drugs within 4 weeks before dosing&#xD;
&#xD;
         24. Intake of over-the-counter (OTC) medications within 2 weeks before dosing&#xD;
&#xD;
         25. Smoking or use of tobacco or nicotine-containing products within 4 weeks before dosing&#xD;
&#xD;
         26. Engagement in strenuous exercise within 2 weeks before dosing (eg, marathon runners,&#xD;
             weight lifters)&#xD;
&#xD;
         27. Currently enrolled in another clinical trial or used any investigational drug or&#xD;
             device within 30 days preceding informed consent&#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>San Antonio</city>
        <state>Texas</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>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 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>QTc Interval</keyword>
  <keyword>Healthy Subjects</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</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/NCT02222324
org study id: E2609-A001-004
nct id: NCT02222324
lead sponsor: 
has dmc: No
This thorough QT (TQT) study will take place in healthy subjects administered single doses of
      study drug. It will be a randomized, double-blind, placebo and active-controlled, 4-treatment
      crossover study. Subjects will be randomized in an equal ratio to one of 12 possible
      treatment sequences. Each treatment sequence will comprise all 4 treatments.
The study will consist of 2 phases: Prerandomization and Randomization. The Prerandomization
      Phase will have 2 periods: Screening (up to 27 days) and Baseline Period 1 (1 day).
      Eligibility will be determined during the Screening Period. The Randomization Phase will
      consist of 8 periods: Treatment Period 1, Baseline Period 2, Treatment Period 2, Baseline
      Period 3, Treatment Period 3, Baseline Period 4, Treatment Period 4, and a Follow-Up Period.
      Each Baseline Period will last 1 day, followed by the corresponding treatment period. On the
      first day of each treatment period, subjects will receive a single dose of the assigned study
      drug. During each treatment period, subjects will be required to stay in the clinical unit
      from the baseline period to 24 hours postdose. Subjects will then be released from the clinic
      and will undergo a washout interval of at least 13 days, during which time they will return
      for additional PK sampling.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline in QTcF obtained from ECGs extracted from the Holter recordings
time frame: Up to 24 hours postdose during each treatment period
description: Holter recordings are taken from a portable device for continuously monitoring various electrical activity of the cardiovascular system for at least 24 hours. Baseline is defined as the mean of predose QTcF values obtained from ECGs extracted from Holter recordings before dosing during each treatment period.
measure: Change from baseline in ECG recordings: PR interval
time frame: Predose and then up to 24 hours postdose in each treatment period
description: Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
measure: Change from baseline in ECG recordings: QRS interval
time frame: Predose and then up to 24 hours postdose in each treatment period
description: Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
measure: Change from baseline in ECG recordings: HR
time frame: Predose and then up 24 hours postdose in each treatment period
description: Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
measure: Change from baseline in ECG recordings: RR interval
time frame: Predose and then at up to 24 hours postdose in each treatment period
description: Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
measure: Change from baseline in ECG recordings: T wave morphology
time frame: Predose and then at up to 24 hours postdose in each treatment period
description: Electrocardiograms will be extracted from the continuous digital recording at 3 predose time points. Other time points may be evaluated as well.
measure: Pharmacokinetics of E2609: Cmax
time frame: Up to 84 Days
description: Maximum drug concentration
measure: Pharmacokinetics of E2609: tmax
time frame: Up to 84 Days
description: Ttime to reach maximum (peak) concentration following drug administration
measure: Pharmacokinetics of E2609: AUC(0-t)
time frame: Up to 84 Days
description: Area under the concentration x time curve from time = 0 to time of last measurable concentration
measure: Pharmacokinetics of E2609: AUC(0-72h)
time frame: Up to 84 Days
description: Area under the concentration x time curve from time = 0 to 72 hours postdose
measure: Pharmacokinetics of E2609: AUC(0-inf)
time frame: Up to 84 Days
description: Area under the concentration x time curve from time = 0 to infinity
measure: Pharmacokinetics of E2609: t1/2
time frame: Up to 84 Days
description: Terminal elimination half-life
measure: Pharmacokinetics of E2609: CL/F
time frame: Up to 84 Days
description: Apparent total clearance following extravascular administration
measure: Pharmacokinetics of E2609: Vz/F
time frame: Up to 84 Days
description: Apparent volume of distribution following extravascular administration
arm group label: Treatment A
arm group type: Placebo Comparator
description: Placebo
arm group label: Treatment B
arm group type: Experimental
description: E2609 Low dose
arm group label: Treatment C
arm group type: Experimental
description: E2609 High dose
arm group label: Treatment D
arm group type: Active Comparator
description: Moxifloxacin
intervention type: Drug
intervention name: Placebo
description: 8 placebo tablets matching E2609
arm group label: Treatment A
intervention type: Drug
intervention name: E2609
description: E2609 will be administered as 8 tablets
arm group label: Treatment B
arm group label: Treatment C
intervention type: Drug
intervention name: Moxifloxacin
description: Administered as 1 tablet with 7 tablets of placebo matching E2609
arm group label: Treatment D
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: Moxifloxacin