Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding Study)

• 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

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: MT-1186; Drug: Rosuvastatin; Drug: Sildenafil; Drug: Furosemide

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adult male volunteers
• Cohort 1: Japanese, Cohort 2: Japanese or Caucasian
• Subjects aged between 20 and 45 years at the time of informed consent
• Subjects who have thoroughly understood the contents of the study and voluntarily provided written informed consent to participate in the study

Exclusion Criteria:

Additional screening criteria check may apply for qualification:

• Subjects with a current or previous history of cardiac, hepatic, renal, gastrointestinal, respiratory, psychiatric/nervous, hematopoietic, or endocrine diseases, and those whom the investigator (or subinvestigator) deems unsuitable for the study
• Body mass index (BMI) of <18.0 or >30.0, or body weight of <50 kg (BMI formula: body weight [kg]/height [m]2, rounded to one decimal place)
• Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs
• Subjects who do not agree to use an effective method of contraception from initiation of study drug administration to 14 days after completion (discontinuation) of study drug administration
• Subjects who have previously received edaravone
• Subjects who have participated in another clinical study and received a study drug within 12 weeks before providing informed consent
• Use of any drug(s) other than the study drug or as-needed use of acetylsalicylic acid within 7 days before the initiation of study drug or victim drug administration
• Use of any alcohol, xanthine, or caffeine-containing product(s) within 24 hours before screening and Day -1 visiting
• Use of any supplement(s) within 7 days before the initiation of study drug or victim drug administration
• Use of grapefruit, grapefruit juice, or any processed food(s) containing these substances during the following periods (Cohort 1: within 7 days before the initiation of victim drug administration, Cohort 2: within 24 hours before each Day -1 visiting)
• Use of any tobacco or nicotine-containing product(s) (Cohort 1: within 12 weeks before the initiation of victim drug administration during the following periods, Cohort 2: within 24 hours before each Day -1 visiting)
• Use of any health food(s) containing St John's Wort (Hypericum perforatum) within 2 weeks before the initiation of victim drug administration (only in Cohort 1)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin, Sildenafil, and MT-1186; 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.	Drug: MT-1186; Suspension; Other Names: Edaravone; Drug: Rosuvastatin; Tablets; Other Names: Crestor; Drug: Sildenafil; Tablets; Other Names: Viagra
Experimental: Furosemide and MT-1186; 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.	Drug: MT-1186; Suspension; Other Names: Edaravone; Drug: Furosemide; Tablets; Other Names: Lasix
Experimental: MT-1186; 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.	Drug: MT-1186; Suspension; Other Names: Edaravone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Rosuvastatin, Sildenafil and Furosemide.	Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
Maximum Plasma Concentration (Cmax) of Rosuvastatin, Sildenafil and Furosemide.	Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
Tmax of Rosuvastatin, Sildenafil and Furosemide.	Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
T1/2 of Rosuvastatin, Sildenafil and Furosemide.	Before rosuvastatin dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before sildenafil dosing and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose, Before furosemide dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hrs post-dose
AUC0-inf of Unchanged Edaravone.	Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Cmax of Unchanged Edaravone.	Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Tmax of Unchanged Edaravone.	Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
T1/2 of Unchanged Edaravone.	Group 1 (Day 6, 9 and 12) and Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
AUC0-inf of Sulfate Conjugate.	Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Cmax of Sulfate Conjugate.	Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Tmax of Sulfate Conjugate.	Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
T1/2 of Sulfate Conjugate.	Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
AUC0-inf of Glucuronide Conjugate.	Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Cmax of Glucuronide Conjugate.	Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
Tmax of Glucuronide Conjugate.	Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
T1/2 of Glucuronide Conjugate.	Group 2 (Day 3 and 6): Pre-dose, 0.083, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 hours post-dose.
AUC0-inf of Unchanged Edaravone.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Cmax of Unchanged Edaravone.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Tmax of Unchanged Edaravone.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
T1/2 of Unchanged Edaravone.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
AUCinf of Sulfate Conjugate and Glucuronide Conjugate.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Cmax of Sulfate Conjugate and Glucuronide Conjugate.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Tmax of Sulfate Conjugate and Glucuronide Conjugate.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
T1/2 of Sulfate Conjugate and Glucuronide Conjugate.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
T1/2 of Glucuronide Conjugate.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Number of Participants With Adverse Events and Adverse Drug Reactions	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

Secondary Outcome Measures

Outcome Measure	Time Frame
Tmax of Unchanged Edaravone.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
T1/2 of Unchanged Edaravone.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
AUCinf of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose
Cmax of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate.	Before dosing, and 0.083, 0.25, 0.5 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose

Collaborators and Investigators

• Sponsor: Tanabe Pharma Corporation
• Investigators: Study Director: General Manager, Tanabe Pharma Corporation

Publications and helpful links

General Publications

• Shimizu H, Nishimura Y, Shiide Y, Akimoto M, Matsuda H, Kato Y, Hirai M. Food Effect Study to Assess the Impact on Edaravone Pharmacokinetic Profiles in Healthy Participants. Clin Ther. 2022 Dec;44(12):1552-1565. doi: 10.1016/j.clinthera.2022.10.001. Epub 2022 Nov 12.
• Shimizu H, Nishimura Y, Shiide Y, Matsuda H, Akimoto M, Matsuda M, Nakamaru Y, Kato Y, Kondo K. Evaluation of Pharmacokinetics, Safety, and Drug-Drug Interactions of an Oral Suspension of Edaravone in Healthy Adults. Clin Pharmacol Drug Dev. 2021 Oct;10(10):1174-1187. doi: 10.1002/cpdd.925. Epub 2021 Mar 11.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2018
• Primary Completion (Actual): December 20, 2018
• Study Completion (Actual): January 8, 2019

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Amides; Aniline Compounds; Amines; Purines; Pyrimidines; Hydrocarbons, Halogenated; Sulfonamides; Sulfanilamides; Sulfones; Pyrazoles; Fluorobenzenes; Hydrocarbons, Fluorinated; Piperazines; Antipyrine; Pyrazolones; Rosuvastatin Calcium; Edaravone; Sildenafil Citrate; Furosemide
• Other Study ID Numbers: MT-1186-J02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No