Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects

To evaluate the single-dose bioequivalence of oral suspension and intravenous (IV) formulation of edaravone in the fasting state in healthy adult subjects

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: MT-1186; Drug: MCI-186

• Study Type: Interventional
• Enrollment (Actual): 42
• 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 or female volunteers
• Japanese
• 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
• Female subjects who do not agree to use an effective method of contraception from screening or 2 weeks before the start of investigational product administration, whichever comes earlier, to 14 days after the completion (or discontinuation) of investigational product administration. Male subjects who do not agree to use an effective method of contraception from the start of investigational product administration to 14 days after the completion (or discontinuation) of investigational product administration
• Subjects who have previously received edaravone
• Subjects who have participated in another clinical study and received an investigational product within 12 weeks before providing informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MT-1186; Healthy subjects were administered a single dose of Edaravone oral suspension	Drug: MT-1186; Oral suspension; Other Names: Edaravone
Active Comparator: MCI-186; Healthy subjects were administered a single dose of Edaravone intravenous formulation	Drug: MCI-186; Intravenous formulation; Other Names: Edaravone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Quantifiable Concentration Time-point (AUC0-t) of Unchanged Edaravone After Oral and Intravenous Administration	The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to Infinity With Extrapolation of the Terminal Phase (AUC0-inf) of Unchanged Edaravone After Oral and Intravenous Administration	The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Maximum Plasma Concentration (Cmax) of Unchanged Edaravone After Oral and Intravenous Administration	The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events and Adverse Drug Reactions		Day 1 to 11
Time to Reach Maximum Plasma Concentration (Tmax)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to 24 Hours (AUC0-24)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; Day 2 at 24 hrs ; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75,2, 3, 4, 6, 8, 12 hrs; Day 2 at 24 hrs.
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Sampling Time-point (for All Time-points) (AUC0-all)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Terminal Elimination Half-life (t1/2)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Elimination Rate Constant From the Central Compartment (Kel)		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Mean Residence Time From Time Zero up to Infinity With Extrapolation of the Terminal Phase (MRT0-inf) of Unchanged Edaravone		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Total Clearance (CL) of Unchanged Edaravone After Intravenous Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Volume of Distribution During Terminal Phase (Vz) of Unchanged Edaravone After Intravenous Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Volume of Distribution at Steady State (Vss) of Unchanged Edaravone After Intravenous Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Apparent Total Clearance (CL/F) of Unchanged Edaravone After Oral Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Unchanged Edaravone After Oral Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Apparent Volume of Distribution at Steady State (Vss/F) of Unchanged Edaravone After Oral Administration		The date of dosing is defined as Day 1. Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Cumulative Amount of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48)		Urine samples are collected: Day1 to 6.
Cumulative Percentage of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48)		Urine samples are collected: Day1 to 6.
Renal Clearance (CLr) of Unchanged Edaravone		Urine samples are collected: Day1 to 6.
Bioavailability (F) of Unchanged Edaravone After Oral Administration	Bioavailability was calculated from ratio of AUC0-inf of unchanged edaravone after oral and intravenous administration.	PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hrs; Day 2 at 24 and 36 hrs; Day 3 at 48 hrs. IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75,2, 3, 4, 6, 8, 12 hrs; Day 2 at 24 and 36 hrs; Day 3 at 48hrs.
AUC0-t of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
AUC0-inf of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.
Cmax of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration		The date of dosing is defined as Day 1. PO: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12 hrs; IV: Day 1 at pre-dose, 0.25, 0.5, 1, 1.083, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12 hrs; Both groups: Day 2 at 24, 36 hrs; Day 3 at 48 hrs.

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation

Publications and helpful links

General Publications

• Shimizu H, Nishimura Y, Shiide Y, Yoshida K, Hirai M, Matsuda M, Nakamaru Y, Kato Y, Kondo K. Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects. Clin Pharmacol Drug Dev. 2021 Oct;10(10):1188-1197. doi: 10.1002/cpdd.952. Epub 2021 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2019
• Primary Completion (Actual): April 21, 2019
• Study Completion (Actual): May 9, 2019

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 30, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

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-J03

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