<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/NCT04481789</url>
  </required_header>
  <id_info>
    <org_study_id>MT-1186-J02</org_study_id>
    <nct_id>NCT04481789</nct_id>
  </id_info>
  <brief_title>Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding Study)</brief_title>
  <official_title>Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding 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>
      -  Cohort 1: To evaluate the drug interactions, safety, and tolerability of oral edaravone&#xD;
           when coadministered with rosuvastatin, sildenafil or furosemide in healthy adult males&#xD;
&#xD;
        -  Cohort 2: To evaluate the pharmacokinetics, safety, and tolerability of oral edaravone&#xD;
           in healthy Japanese and Caucasian adult males&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 17, 2018</start_date>
  <completion_date type="Actual">January 8, 2019</completion_date>
  <primary_completion_date type="Actual">December 20, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Cohort 1 is open-label, non-randomized, sequential, and add-on study. Cohort 2 is single-dose, open-label, randomized, and cross-over study.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PK parameters - Area under the concentration versus time curve from time zero to infinity (AUC 0-inf) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide</measure>
    <time_frame>Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Maximum plasma concentration (Cmax) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide</measure>
    <time_frame>Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Time to reach maximum plasma concentration (tmax) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide</measure>
    <time_frame>Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PK parameters - Terminal elimination half-life (t1/2) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide</measure>
    <time_frame>Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse events and adverse drug reactions</measure>
    <time_frame>Day 1 to 20 in group 1 of cohort 1, Day 1 to 14 in group 2 of cohort 1, Day 1 to 14 of cohort 2</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Healthy Adult Subjects</condition>
  <arm_group>
    <arm_group_label>Rosuvastatin, Sildenafil, and MT-1186</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1 of Cohort 1:&#xD;
A single-sequence study in which healthy male subjects receive a single dose of rosuvastatin on Day 1 followed by a single dose of sildenafil on Day 4. MT-1186 will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Furosemide and MT-1186</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 2 of Cohort 1:&#xD;
A single-sequence study in which healthy male subjects receive a single dose of furosemide on Day 1. MT-1186 will be administered from Day 3 to 7 with co-administration of furosemide on Day 6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MT-1186</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 2:&#xD;
A three-way crossover study in which Japanese healthy male subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Caucasian healthy male subjects receive a single dose of MT-1186 at the same period with Japanese subjects under the corresponding condition on Day 1, 4, or 7 according to their treatment schedule.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MT-1186</intervention_name>
    <description>Suspension</description>
    <arm_group_label>Furosemide and MT-1186</arm_group_label>
    <arm_group_label>MT-1186</arm_group_label>
    <arm_group_label>Rosuvastatin, Sildenafil, and MT-1186</arm_group_label>
    <other_name>Edaravone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>Tablets</description>
    <arm_group_label>Rosuvastatin, Sildenafil, and MT-1186</arm_group_label>
    <other_name>Crestor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sildenafil</intervention_name>
    <description>Tablets</description>
    <arm_group_label>Rosuvastatin, Sildenafil, and MT-1186</arm_group_label>
    <other_name>Viagra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Furosemide</intervention_name>
    <description>Tablets</description>
    <arm_group_label>Furosemide and MT-1186</arm_group_label>
    <other_name>Lasix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adult male volunteers&#xD;
&#xD;
          -  Cohort 1: Japanese, Cohort 2: 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;
&#xD;
          -  Use of any drug(s) other than the study drug or as-needed use of acetylsalicylic acid&#xD;
             within 7 days before the initiation of study drug or victim drug administration&#xD;
&#xD;
          -  Use of any alcohol, xanthine, or caffeine-containing product(s) within 24 hours before&#xD;
             screening and Day -1 visiting&#xD;
&#xD;
          -  Use of any supplement(s) within 7 days before the initiation of study drug or victim&#xD;
             drug administration&#xD;
&#xD;
          -  Use of grapefruit, grapefruit juice, or any processed food(s) containing these&#xD;
             substances during the following periods (Cohort 1: within 7 days before the initiation&#xD;
             of victim drug administration, Cohort 2: within 24 hours before each Day -1 visiting)&#xD;
&#xD;
          -  Use of any tobacco or nicotine-containing product(s) (Cohort 1: within 12 weeks before&#xD;
             the initiation of victim drug administration during the following periods, Cohort 2:&#xD;
             within 24 hours before each Day -1 visiting)&#xD;
&#xD;
          -  Use of any health food(s) containing St John's Wort (Hypericum perforatum) within 2&#xD;
             weeks before the initiation of victim drug administration (only in Cohort 1)&#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>Tokyo</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 17, 2020</last_update_submitted>
  <last_update_submitted_qc>July 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 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>Furosemide</mesh_term>
    <mesh_term>Sildenafil Citrate</mesh_term>
    <mesh_term>Edaravone</mesh_term>
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 11, 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/NCT04481789
org study id: MT-1186-J02
nct id: NCT04481789
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
-  Cohort 1: To evaluate the drug interactions, safety, and tolerability of oral edaravone
           when coadministered with rosuvastatin, sildenafil or furosemide in healthy adult males

        -  Cohort 2: To evaluate the pharmacokinetics, safety, and tolerability of oral edaravone
           in healthy Japanese and Caucasian adult males
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Cohort 1 is open-label, non-randomized, sequential, and add-on study. Cohort 2 is single-dose, open-label, randomized, and cross-over study.
primary purpose: Other
masking: None (Open Label)
measure: PK parameters - Area under the concentration versus time curve from time zero to infinity (AUC 0-inf) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide
time frame: Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2
measure: PK parameters - Maximum plasma concentration (Cmax) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide
time frame: Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2
measure: PK parameters - Time to reach maximum plasma concentration (tmax) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide
time frame: Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2
measure: PK parameters - Terminal elimination half-life (t1/2) of rosuvastatin, sildenafil, furosemide, and unchanged edaravone, sulfate, glucuronide
time frame: Day 1 to 14 in group 1 of cohort 1, Day 1 to 8 in group 2 of cohort 1, Day 1 to 9 in cohort 2
measure: Number of Participants with Adverse events and adverse drug reactions
time frame: Day 1 to 20 in group 1 of cohort 1, Day 1 to 14 in group 2 of cohort 1, Day 1 to 14 of cohort 2
arm group label: Rosuvastatin, Sildenafil, and MT-1186
arm group type: Experimental
description: Group 1 of Cohort 1:
A single-sequence study in which healthy male subjects receive a single dose of rosuvastatin on Day 1 followed by a single dose of sildenafil on Day 4. MT-1186 will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively.
arm group label: Furosemide and MT-1186
arm group type: Experimental
description: Group 2 of Cohort 1:
A single-sequence study in which healthy male subjects receive a single dose of furosemide on Day 1. MT-1186 will be administered from Day 3 to 7 with co-administration of furosemide on Day 6.
arm group label: MT-1186
arm group type: Experimental
description: Cohort 2:
A three-way crossover study in which Japanese healthy male subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Caucasian healthy male subjects receive a single dose of MT-1186 at the same period with Japanese subjects under the corresponding condition on Day 1, 4, or 7 according to their treatment schedule.
intervention type: Drug
intervention name: MT-1186
description: Suspension
arm group label: Furosemide and MT-1186
arm group label: MT-1186
arm group label: Rosuvastatin, Sildenafil, and MT-1186
other name: Edaravone
intervention type: Drug
intervention name: Rosuvastatin
description: Tablets
arm group label: Rosuvastatin, Sildenafil, and MT-1186
other name: Crestor
intervention type: Drug
intervention name: Sildenafil
description: Tablets
arm group label: Rosuvastatin, Sildenafil, and MT-1186
other name: Viagra
intervention type: Drug
intervention name: Furosemide
description: Tablets
arm group label: Furosemide and MT-1186
other name: Lasix
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: Furosemide
mesh term: Sildenafil Citrate
mesh term: Edaravone
mesh term: Rosuvastatin Calcium
sharing ipd: No
submitted: May 11, 2023