<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/NCT04481750</url>
  </required_header>
  <id_info>
    <org_study_id>MT-1186-J01</org_study_id>
    <nct_id>NCT04481750</nct_id>
  </id_info>
  <brief_title>Study of Oral Edaravone in Healthy Adult Males</brief_title>
  <official_title>Phase I Study of Oral Edaravone in Healthy Adult Males (Single- and Multiple-dose Study)</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 pharmacokinetics safety, and tolerability of single and multiple doses of&#xD;
      edaravone solution and suspension in healthy adult males&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 20, 2018</start_date>
  <completion_date type="Actual">August 3, 2018</completion_date>
  <primary_completion_date type="Actual">August 3, 2018</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>Other</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Single Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Adverse events and adverse drug reactions</measure>
    <time_frame>Day 1 to 8 in part 1, day1 to 12 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentrations</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
    <description>Plasma concentrations of unchanged edaravone, sulfate, and glucuronide for PK analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Area under the concentration versus time curve (AUC) of unchanged edaravone, sulfate, and glucuronide</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
    <description>AUC from time zero to the last measured time point (AUC 0-last), AUC from time zero to 12 hours (AUC 0-12), from time zero to 24 hours (AUC 0-24), and AUC from time zero to infinity (AUC 0-inf)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Maximum plasma concentration (Cmax) of unchanged edaravone, sulfate, and glucuronide</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Minimum plasma concentration (Ctrough) of unchanged edaravone, sulfate, and glucuronide</measure>
    <time_frame>Day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Time to reach maximum plasma concentration (tmax) of unchanged edaravone, sulfate, and glucuronide</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Terminal elimination half-life (t1/2) of unchanged edaravone, sulfate, and glucuronide</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Lambda-z of unchanged edaravone, sulfate, and glucuronide</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Mean residence time (MRT) of unchanged edaravone</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Apparent total clearance (CL/F) of unchanged edaravone</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Apparent distribution volume at elimination phase (Vz/F) of unchanged edaravone</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Apparent distribution volume at steady state (Vss/F) of unchanged edaravone</measure>
    <time_frame>Day 1 to 3 in part 1, day 1 to 7 in part 2</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Day 1 to 3 in cohort 4, 5 and 6 in part 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PR interval</measure>
    <time_frame>Day 1 to 3 in cohort 4, 5 and 6 in part 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QT interval</measure>
    <time_frame>Day 1 to 3 in cohort 4, 5 and 6 in part 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QTcF</measure>
    <time_frame>Day 1 to 3 in cohort 4, 5 and 6 in part 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QRS interval</measure>
    <time_frame>Day 1 to 3 in cohort 4, 5 and 6 in part 1</time_frame>
  </secondary_outcome>
  <number_of_arms>10</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Healthy Adult Subjects</condition>
  <arm_group>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S3-1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S3-2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S4)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S5)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S6)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S7)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Caucasian male subjects receive a single dose of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple doses MT-1186 (Part 2, Cohort M1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Multiple doses MT-1186 (Part 2, Cohort M2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MT-1186</intervention_name>
    <description>Solution or suspension</description>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S1)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S2)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S3-1)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S3-2)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S4)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S5)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S6)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S7)</arm_group_label>
    <arm_group_label>Multiple doses MT-1186 (Part 2, Cohort M1)</arm_group_label>
    <arm_group_label>Multiple doses MT-1186 (Part 2, Cohort M2)</arm_group_label>
    <other_name>Edaravone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MT-1186-matching placebo</intervention_name>
    <description>Solution or suspension</description>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S1)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S2)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S3-1)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S3-2)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S4)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S5)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S6)</arm_group_label>
    <arm_group_label>A single dose MT-1186 (Part 1, Cohort S7)</arm_group_label>
    <arm_group_label>Multiple doses MT-1186 (Part 2, Cohort M1)</arm_group_label>
    <arm_group_label>Multiple doses MT-1186 (Part 2, Cohort M2)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Additional screening criteria check may apply for qualification:&#xD;
&#xD;
          -  Healthy adult male volunteers&#xD;
&#xD;
          -  Japanese or Caucasian&#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:&#xD;
&#xD;
        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;
          -  Subjects who do not agree to use an effective method of contraception from initiation&#xD;
             of study drug administration to 14 days after completion (discontinuation) of study&#xD;
             drug administration&#xD;
&#xD;
          -  Subjects who have previously received edaravone&#xD;
&#xD;
          -  Subjects who have participated in another clinical study and received a study drug&#xD;
             within 12 weeks before providing informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>General Manager</last_name>
    <role>Study Director</role>
    <affiliation>Mitsubishi Tanabe Pharma Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site</name>
      <address>
        <city>Osaka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 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>May 12, 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/NCT04481750
org study id: MT-1186-J01
nct id: NCT04481750
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the pharmacokinetics safety, and tolerability of single and multiple doses of
      edaravone solution and suspension in healthy adult males
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Single (Participant)
masking description: Single Blind
measure: Number of Participants with Adverse events and adverse drug reactions
time frame: Day 1 to 8 in part 1, day1 to 12 in part 2
measure: Plasma concentrations
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
description: Plasma concentrations of unchanged edaravone, sulfate, and glucuronide for PK analysis
measure: PK parameters - Area under the concentration versus time curve (AUC) of unchanged edaravone, sulfate, and glucuronide
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
description: AUC from time zero to the last measured time point (AUC 0-last), AUC from time zero to 12 hours (AUC 0-12), from time zero to 24 hours (AUC 0-24), and AUC from time zero to infinity (AUC 0-inf)
measure: PK parameters - Maximum plasma concentration (Cmax) of unchanged edaravone, sulfate, and glucuronide
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
measure: PK parameters - Minimum plasma concentration (Ctrough) of unchanged edaravone, sulfate, and glucuronide
time frame: Day 1 to 7 in part 2
measure: PK parameters - Time to reach maximum plasma concentration (tmax) of unchanged edaravone, sulfate, and glucuronide
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
measure: PK parameters - Terminal elimination half-life (t1/2) of unchanged edaravone, sulfate, and glucuronide
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
measure: PK parameters - Lambda-z of unchanged edaravone, sulfate, and glucuronide
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
measure: PK parameters - Mean residence time (MRT) of unchanged edaravone
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
measure: PK parameters - Apparent total clearance (CL/F) of unchanged edaravone
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
measure: PK parameters - Apparent distribution volume at elimination phase (Vz/F) of unchanged edaravone
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
measure: PK parameters - Apparent distribution volume at steady state (Vss/F) of unchanged edaravone
time frame: Day 1 to 3 in part 1, day 1 to 7 in part 2
measure: Heart rate
time frame: Day 1 to 3 in cohort 4, 5 and 6 in part 1
measure: PR interval
time frame: Day 1 to 3 in cohort 4, 5 and 6 in part 1
measure: QT interval
time frame: Day 1 to 3 in cohort 4, 5 and 6 in part 1
measure: QTcF
time frame: Day 1 to 3 in cohort 4, 5 and 6 in part 1
measure: QRS interval
time frame: Day 1 to 3 in cohort 4, 5 and 6 in part 1
arm group label: A single dose MT-1186 (Part 1, Cohort S1)
arm group type: Experimental
description: Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
arm group label: A single dose MT-1186 (Part 1, Cohort S2)
arm group type: Experimental
description: Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
arm group label: A single dose MT-1186 (Part 1, Cohort S3-1)
arm group type: Experimental
description: Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.
arm group label: A single dose MT-1186 (Part 1, Cohort S3-2)
arm group type: Experimental
description: Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.
arm group label: A single dose MT-1186 (Part 1, Cohort S4)
arm group type: Experimental
description: Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
arm group label: A single dose MT-1186 (Part 1, Cohort S5)
arm group type: Experimental
description: Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
arm group label: A single dose MT-1186 (Part 1, Cohort S6)
arm group type: Experimental
description: Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.
arm group label: A single dose MT-1186 (Part 1, Cohort S7)
arm group type: Experimental
description: Healthy Caucasian male subjects receive a single dose of MT-1186 or matching placebo.
arm group label: Multiple doses MT-1186 (Part 2, Cohort M1)
arm group type: Experimental
description: Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo.
arm group label: Multiple doses MT-1186 (Part 2, Cohort M2)
arm group type: Experimental
description: Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo
intervention type: Drug
intervention name: MT-1186
description: Solution or suspension
arm group label: A single dose MT-1186 (Part 1, Cohort S1)
arm group label: A single dose MT-1186 (Part 1, Cohort S2)
arm group label: A single dose MT-1186 (Part 1, Cohort S3-1)
arm group label: A single dose MT-1186 (Part 1, Cohort S3-2)
arm group label: A single dose MT-1186 (Part 1, Cohort S4)
arm group label: A single dose MT-1186 (Part 1, Cohort S5)
arm group label: A single dose MT-1186 (Part 1, Cohort S6)
arm group label: A single dose MT-1186 (Part 1, Cohort S7)
arm group label: Multiple doses MT-1186 (Part 2, Cohort M1)
arm group label: Multiple doses MT-1186 (Part 2, Cohort M2)
other name: Edaravone
intervention type: Drug
intervention name: MT-1186-matching placebo
description: Solution or suspension
arm group label: A single dose MT-1186 (Part 1, Cohort S1)
arm group label: A single dose MT-1186 (Part 1, Cohort S2)
arm group label: A single dose MT-1186 (Part 1, Cohort S3-1)
arm group label: A single dose MT-1186 (Part 1, Cohort S3-2)
arm group label: A single dose MT-1186 (Part 1, Cohort S4)
arm group label: A single dose MT-1186 (Part 1, Cohort S5)
arm group label: A single dose MT-1186 (Part 1, Cohort S6)
arm group label: A single dose MT-1186 (Part 1, Cohort S7)
arm group label: Multiple doses MT-1186 (Part 2, Cohort M1)
arm group label: Multiple doses MT-1186 (Part 2, Cohort M2)
criteria: 
gender: Male
minimum age: 20 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: General Manager
role: Study Director
affiliation: Mitsubishi Tanabe Pharma Corporation
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Edaravone
sharing ipd: No
submitted: May 12, 2023