Study of Oral Edaravone in Healthy Adult Males

Phase I Study of Oral Edaravone in Healthy Adult Males (Single- and Multiple-dose Study)

To evaluate the pharmacokinetics safety, and tolerability of single and multiple doses of edaravone solution and suspension in healthy adult males

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: MT-1186; Drug: MT-1186-matching placebo

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan
    • Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Additional screening criteria check may apply for qualification:

• Healthy adult male volunteers
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A single dose MT-1186 (Part 1, Cohort S1); Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: A single dose MT-1186 (Part 1, Cohort S2); Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: A single dose MT-1186 (Part 1, Cohort S3-1); Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: A single dose MT-1186 (Part 1, Cohort S3-2); Healthy Japanese male subjects receive doses of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: A single dose MT-1186 (Part 1, Cohort S4); Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: A single dose MT-1186 (Part 1, Cohort S5); Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: A single dose MT-1186 (Part 1, Cohort S6); Healthy Japanese male subjects receive a single dose of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: A single dose MT-1186 (Part 1, Cohort S7); Healthy Caucasian male subjects receive a single dose of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: Multiple doses MT-1186 (Part 2, Cohort M1); Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo.	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension
EXPERIMENTAL: Multiple doses MT-1186 (Part 2, Cohort M2); Healthy Japanese male subjects receive multiple doses of MT-1186 or matching placebo	Drug: MT-1186; Solution or suspension; Other Names: Edaravone; Drug: MT-1186-matching placebo; Solution or suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse events and adverse drug reactions		Day 1 to 8 in part 1, day1 to 12 in part 2
Plasma concentrations	Plasma concentrations of unchanged edaravone, sulfate, and glucuronide for PK analysis	Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Area under the concentration versus time curve (AUC) of unchanged edaravone, sulfate, and glucuronide	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)	Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Maximum plasma concentration (Cmax) of unchanged edaravone, sulfate, and glucuronide		Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Minimum plasma concentration (Ctrough) of unchanged edaravone, sulfate, and glucuronide		Day 1 to 7 in part 2
PK parameters - Time to reach maximum plasma concentration (tmax) of unchanged edaravone, sulfate, and glucuronide		Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Terminal elimination half-life (t1/2) of unchanged edaravone, sulfate, and glucuronide		Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Lambda-z of unchanged edaravone, sulfate, and glucuronide		Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Mean residence time (MRT) of unchanged edaravone		Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Apparent total clearance (CL/F) of unchanged edaravone		Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Apparent distribution volume at elimination phase (Vz/F) of unchanged edaravone		Day 1 to 3 in part 1, day 1 to 7 in part 2
PK parameters - Apparent distribution volume at steady state (Vss/F) of unchanged edaravone		Day 1 to 3 in part 1, day 1 to 7 in part 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Heart rate	Day 1 to 3 in cohort 4, 5 and 6 in part 1
PR interval	Day 1 to 3 in cohort 4, 5 and 6 in part 1
QT interval	Day 1 to 3 in cohort 4, 5 and 6 in part 1
QTcF	Day 1 to 3 in cohort 4, 5 and 6 in part 1
QRS interval	Day 1 to 3 in cohort 4, 5 and 6 in part 1

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation

Publications and helpful links

General Publications

• 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): March 20, 2018
• Primary Completion (ACTUAL): August 3, 2018
• Study Completion (ACTUAL): August 3, 2018

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): July 29, 2020
• Last Update Submitted That Met QC Criteria: July 27, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: MT-1186-J01

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