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

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

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

Conditions
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Healthy Adult Subjects

Intervention / Treatment
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* Drug: MT-1186
* Drug: MCI-186


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters - 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 |  | Day 1 to 2 | 
| PK parameters - 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 |  | Day 1 to 2 | 
| PK parameters - Maximum plasma concentration (Cmax) of unchanged edaravone after oral and intravenous administration |  | Day 1 to 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters - Area under the plasma concentration versus time curve from time zero up to 24 hours (AUC0-24) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Area under the plasma concentration versus time curve from time zero up to the last sampling time-point (for all time-points) (AUC0-all) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Time to reach maximum plasma concentration (tmax) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Terminal elimination half-life (t1/2) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Elimination rate constant from the central compartment (Kel) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Mean residence time (MRT) of unchanged edaravone after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Total clearance (CL) of unchanged edaravone after intravenous administration |  | Day 1 to 2 | 
| PK parameters - Volume of distribution during terminal phase (Vz) of unchanged edaravone after intravenous administration |  | Day 1 to 2 | 
| PK parameters -Volume of distribution at steady state (Vss) of unchanged edaravone after intravenous administration |  | Day 1 to 2 | 
| PK parameters - Apparent total clearance (CL/F) of unchanged edaravone after oral administration |  | Day 1 to 2 | 
| PK parameters - Apparent volume of distribution during terminal phase (Vz/F) of unchanged edaravone after oral administration |  | Day 1 to 2 | 
| PK parameters - Apparent volume of distribution at steady state (Vss/F) of unchanged edaravone after oral administration |  | Day 1 to 2 | 
| PK parameters -Cumulative amount of drug excreted in urine (Ae) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Cumulative percentage of drug excreted in urine (Ae%) of unchanged edaravone, sulfate, and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Renal clearance (CLr) of unchanged edaravone after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Bioavailability (F) of unchanged edaravone |  | Day 1 to 2 | 
| PK parameters - Area under the plasma concentration versus time curve from time zero up to the last quantifiable concentration time-point (AUC0-t) of sulfate and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Area under the plasma concentration versus time curve from time zero up to infinity with extrapolation of the terminal phase (AUC0-inf) of sulfate and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| PK parameters - Maximum plasma concentration (Cmax) of sulfate and glucuronide conjugates after oral and intravenous administration |  | Day 1 to 2 | 
| Number of Participants with Adverse events and adverse drug reactions |  | Day 1 to 11 |