<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/NCT04493281</url>
  </required_header>
  <id_info>
    <org_study_id>MT-1186-J03</org_study_id>
    <nct_id>NCT04493281</nct_id>
  </id_info>
  <brief_title>Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects</brief_title>
  <official_title>Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mitsubishi Tanabe Pharma Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mitsubishi Tanabe Pharma Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the single-dose bioequivalence of oral suspension and intravenous (IV)&#xD;
      formulation of edaravone in the fasting state in healthy adult subjects&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 22, 2019</start_date>
  <completion_date type="Actual">May 9, 2019</completion_date>
  <primary_completion_date type="Actual">April 21, 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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PK parameters - Area under the plasma concentration versus time curve from time zero up to the last quantifiable concentration time-point (AUC0-t) of unchanged edaravone after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Area under the plasma concentration versus time curve from time zero up to infinity with extrapolation of the terminal phase (AUC0-inf) of unchanged edaravone after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Maximum plasma concentration (Cmax) of unchanged edaravone after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Area under the plasma concentration versus time curve from time zero up to the last sampling time-point (for all time-points) (AUC0-all) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Time to reach maximum plasma concentration (tmax) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Terminal elimination half-life (t1/2) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Elimination rate constant from the central compartment (Kel) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Mean residence time (MRT) of unchanged edaravone after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Total clearance (CL) of unchanged edaravone after intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Volume of distribution during terminal phase (Vz) of unchanged edaravone after intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters -Volume of distribution at steady state (Vss) of unchanged edaravone after intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Apparent total clearance (CL/F) of unchanged edaravone after oral administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Apparent volume of distribution during terminal phase (Vz/F) of unchanged edaravone after oral administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Apparent volume of distribution at steady state (Vss/F) of unchanged edaravone after oral administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters -Cumulative amount of drug excreted in urine (Ae) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Cumulative percentage of drug excreted in urine (Ae%) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Renal clearance (CLr) of unchanged edaravone after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Bioavailability (F) of unchanged edaravone</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Area under the plasma concentration versus time curve from time zero up to the last quantifiable concentration time-point (AUC0-t) of sulfate and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Area under the plasma concentration versus time curve from time zero up to infinity with extrapolation of the terminal phase (AUC0-inf) of sulfate and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters - Maximum plasma concentration (Cmax) of sulfate and glucuronide conjugates after oral and intravenous administration</measure>
    <time_frame>Day 1 to 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse events and adverse drug reactions</measure>
    <time_frame>Day 1 to 11</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Healthy Adult Subjects</condition>
  <arm_group>
    <arm_group_label>MT-1186</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy subjects were administered a single dose of Edaravone oral suspension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MCI-186</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy subjects were administered a single dose of Edaravone intravenous formulation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MT-1186</intervention_name>
    <description>Oral suspension</description>
    <arm_group_label>MT-1186</arm_group_label>
    <other_name>Edaravone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MCI-186</intervention_name>
    <description>Intravenous formulation</description>
    <arm_group_label>MCI-186</arm_group_label>
    <other_name>Edaravone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adult male or female volunteers&#xD;
&#xD;
          -  Japanese&#xD;
&#xD;
          -  Subjects aged between 20 and 45 years at the time of informed consent&#xD;
&#xD;
          -  Subjects who have thoroughly understood the contents of the study and voluntarily&#xD;
             provided written informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria: Additional screening criteria check may apply for qualification:&#xD;
&#xD;
          -  Subjects with a current or previous history of cardiac, hepatic, renal,&#xD;
             gastrointestinal, respiratory, psychiatric/nervous, hematopoietic, or endocrine&#xD;
             diseases, and those whom the investigator (or subinvestigator) deems unsuitable for&#xD;
             the study&#xD;
&#xD;
          -  Body mass index (BMI) of &lt;18.0 or &gt;30.0, or body weight of &lt;50 kg (BMI formula: body&#xD;
             weight [kg]/height [m]2, rounded to one decimal place)&#xD;
&#xD;
          -  Subjects who have undergone any surgery known to affect the gastrointestinal&#xD;
             absorption of drugs&#xD;
&#xD;
          -  Female subjects who do not agree to use an effective method of contraception from&#xD;
             screening or 2 weeks before the start of investigational product administration,&#xD;
             whichever comes earlier, to 14 days after the completion (or discontinuation) of&#xD;
             investigational product administration. Male subjects who do not agree to use an&#xD;
             effective method of contraception from the start of investigational product&#xD;
             administration to 14 days after the completion (or discontinuation) of investigational&#xD;
             product administration&#xD;
&#xD;
          -  Subjects who have previously received edaravone&#xD;
&#xD;
          -  Subjects who have participated in another clinical study and received an&#xD;
             investigational product within 12 weeks before providing informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Investigational site</name>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>August 3, 2020</last_update_submitted>
  <last_update_submitted_qc>August 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2020</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>Edaravone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>March 29, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04493281
org study id: MT-1186-J03
nct id: NCT04493281
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the single-dose bioequivalence of oral suspension and intravenous (IV)
      formulation of edaravone in the fasting state in healthy adult subjects
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: PK parameters - Area under the plasma concentration versus time curve from time zero up to the last quantifiable concentration time-point (AUC0-t) of unchanged edaravone after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Area under the plasma concentration versus time curve from time zero up to infinity with extrapolation of the terminal phase (AUC0-inf) of unchanged edaravone after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Maximum plasma concentration (Cmax) of unchanged edaravone after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Area under the plasma concentration versus time curve from time zero up to the last sampling time-point (for all time-points) (AUC0-all) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Time to reach maximum plasma concentration (tmax) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Terminal elimination half-life (t1/2) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Elimination rate constant from the central compartment (Kel) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Mean residence time (MRT) of unchanged edaravone after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Total clearance (CL) of unchanged edaravone after intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Volume of distribution during terminal phase (Vz) of unchanged edaravone after intravenous administration
time frame: Day 1 to 2
measure: PK parameters -Volume of distribution at steady state (Vss) of unchanged edaravone after intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Apparent total clearance (CL/F) of unchanged edaravone after oral administration
time frame: Day 1 to 2
measure: PK parameters - Apparent volume of distribution during terminal phase (Vz/F) of unchanged edaravone after oral administration
time frame: Day 1 to 2
measure: PK parameters - Apparent volume of distribution at steady state (Vss/F) of unchanged edaravone after oral administration
time frame: Day 1 to 2
measure: PK parameters -Cumulative amount of drug excreted in urine (Ae) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Cumulative percentage of drug excreted in urine (Ae%) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Renal clearance (CLr) of unchanged edaravone after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Bioavailability (F) of unchanged edaravone
time frame: Day 1 to 2
measure: PK parameters - Area under the plasma concentration versus time curve from time zero up to the last quantifiable concentration time-point (AUC0-t) of sulfate and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Area under the plasma concentration versus time curve from time zero up to infinity with extrapolation of the terminal phase (AUC0-inf) of sulfate and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: PK parameters - Maximum plasma concentration (Cmax) of sulfate and glucuronide conjugates after oral and intravenous administration
time frame: Day 1 to 2
measure: Number of Participants with Adverse events and adverse drug reactions
time frame: Day 1 to 11
arm group label: MT-1186
arm group type: Experimental
description: Healthy subjects were administered a single dose of Edaravone oral suspension
arm group label: MCI-186
arm group type: Active Comparator
description: Healthy subjects were administered a single dose of Edaravone intravenous formulation
intervention type: Drug
intervention name: MT-1186
description: Oral suspension
arm group label: MT-1186
other name: Edaravone
intervention type: Drug
intervention name: MCI-186
description: Intravenous formulation
arm group label: MCI-186
other name: Edaravone
criteria: 
gender: All
minimum age: 20 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Edaravone
sharing ipd: No
submitted: March 29, 2023