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

NCT04481789 | Completed Phase 1 Results

• 1 other identifier: MT-1186-J02
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

• 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

Conditions

Healthy Adult Subjects

Outcome Measures

Primary Outcomes (26)

• 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 Outcomes (4)

• 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

• 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

Study Arms (3)

Rosuvastatin, Sildenafil, and MT-1186

EXPERIMENTAL

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; Drug: Rosuvastatin; Drug: Sildenafil

Furosemide and MT-1186

EXPERIMENTAL

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; Drug: Furosemide

MT-1186

EXPERIMENTAL

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

Interventions

MT-1186 DRUG

Suspension

Also known as: Edaravone

Furosemide and MT-1186; MT-1186; Rosuvastatin, Sildenafil, and MT-1186

Rosuvastatin DRUG

Tablets

Also known as: Crestor

Rosuvastatin, Sildenafil, and MT-1186

Sildenafil DRUG

Tablets

Also known as: Viagra

Rosuvastatin, Sildenafil, and MT-1186

Furosemide DRUG

Tablets

Also known as: Lasix

Furosemide and MT-1186

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Tanabe Pharma Corporation: lead

Study Sites (1)

Investigational site

Tokyo, Japan

Location

Related Publications (2)

• 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.

  PMID: 36376130 RESULT

• 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.

  PMID: 33704925 RESULT

MeSH Terms

Interventions

Edaravone; Rosuvastatin Calcium; Sildenafil Citrate; Furosemide

Intervention Hierarchy (Ancestors)

Antipyrine; Pyrazolones; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Piperazines; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfanilamides; Aniline Compounds; Amines

Results Point of Contact

• Title: Clinical Trials, Information Desk
• Organization: Tanabe Pharma Corporation

cti-inq-ml.JP@ml.tanabe-pharma.com

Please e-mail

Study Officials

• General Manager

  Tanabe Pharma Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Cohort 1 is open-label, non-randomized, sequential, and add-on study. Cohort 2 is single-dose, open-label, randomized, and cross-over study.

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 22, 2020
• Study Start: October 17, 2018
• Primary Completion: December 20, 2018
• Study Completion: January 8, 2019
• Last Updated: January 7, 2026
• Results First Posted: August 2, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)