Trial Outcomes & Findings for Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects (NCT NCT04493281)

NCT ID: NCT04493281

Last Updated: 2026-01-07

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 42 participants
• Primary outcome timeframe: 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.
• Results posted on: 2026-01-07

Participant Flow

Participant milestones

Measure	Edaravone Oral Suspensione First, Then Edaravone IV Formulation Period 1: a single dose of Edaravone oral suspension (105 mg) . Period 2: a single dose of Edaravone IV formulation (60 mg/60 min).	Edaravone IV Formulation First, Then Edaravone Oral Suspension Period 1: a single dose of Edaravone IV formulation (60 mg/60 min). Period 2: a single dose of Edaravone oral suspension (105 mg) .
Period 1 STARTED	21	21
Period 1 COMPLETED	21	21
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	21	21
Period 2 COMPLETED	21	21
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Edaravone Oral Suspensione First, Then Edaravone IV Formulation n=21 Participants Period 1: a single dose of Edaravone oral suspension (105 mg) . Period 2: a single dose of Edaravone IV formulation (60 mg/60 min).	Edaravone IV Formulation First, Then Edaravone Oral Suspension n=21 Participants Period 1: a single dose of Edaravone IV formulation (60 mg/60 min). Period 2: a single dose of Edaravone oral suspension (105 mg) .	Total n=42 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=37 Participants	21 Participants n=56 Participants	42 Participants n=95 Participants
Age, Categorical >=65 years	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants
Sex: Female, Male Female	7 Participants n=37 Participants	7 Participants n=56 Participants	14 Participants n=95 Participants
Sex: Female, Male Male	14 Participants n=37 Participants	14 Participants n=56 Participants	28 Participants n=95 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants
Race (NIH/OMB) Asian	21 Participants n=37 Participants	21 Participants n=56 Participants	42 Participants n=95 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants
Race (NIH/OMB) Black or African American	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants
Race (NIH/OMB) White	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants
Race (NIH/OMB) More than one race	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants

PRIMARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
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	1743 ng·h/mL Standard Deviation 534	1720 ng·h/mL Standard Deviation 326

PRIMARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
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	1762 ng·h/mL Standard Deviation 540	1736 ng·h/mL Standard Deviation 331

PRIMARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Maximum Plasma Concentration (Cmax) of Unchanged Edaravone After Oral and Intravenous Administration	1656 ng/mL Standard Deviation 733.6	1253 ng/mL Standard Deviation 228.9

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Time to Reach Maximum Plasma Concentration (Tmax) Unchanged edaravone	0.50 h Interval 0.25 to 0.75	1.00 h Interval 0.98 to 1.02
Time to Reach Maximum Plasma Concentration (Tmax) Sulfate conjugate	0.75 h Interval 0.5 to 1.0	1.08 h Interval 0.98 to 1.25
Time to Reach Maximum Plasma Concentration (Tmax) Glucuronide Conjugate	0.75 h Interval 0.25 to 1.0	1.08 h Interval 1.0 to 1.27

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to 24 Hours (AUC0-24) Unchanged edaravone	1735 ng·h/mL Standard Deviation 523	1714 ng·h/mL Standard Deviation 317
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to 24 Hours (AUC0-24) Sulfate conjugate	19837 ng·h/mL Standard Deviation 5185	14830 ng·h/mL Standard Deviation 3519
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to 24 Hours (AUC0-24) Glucuronide Conjugate	3917 ng·h/mL Standard Deviation 727	2288 ng·h/mL Standard Deviation 479

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Sampling Time-point (for All Time-points) (AUC0-all) Unchanged edaravone	1752 ng·h/mL Standard Deviation 532	1727 ng·h/mL Standard Deviation 323
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Sampling Time-point (for All Time-points) (AUC0-all) Sulfate conjugate	20035 ng·h/mL Standard Deviation 5252	15025 ng·h/mL Standard Deviation 3575
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Sampling Time-point (for All Time-points) (AUC0-all) Glucuronide Conjugate	3927 ng·h/mL Standard Deviation 730	2297 ng·h/mL Standard Deviation 481

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Terminal Elimination Half-life (t1/2) Unchanged edaravone	9.75 h Standard Deviation 8.47	8.82 h Standard Deviation 8.33
Terminal Elimination Half-life (t1/2) Sulfate conjugate	5.77 h Standard Deviation 1.85	7.58 h Standard Deviation 2.39
Terminal Elimination Half-life (t1/2) Glucuronide Conjugate	3.75 h Standard Deviation 0.55	3.69 h Standard Deviation 0.48

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Elimination Rate Constant From the Central Compartment (Kel) Sulfate conjugate	0.1295 1/h Standard Deviation 0.0318	0.1010 1/h Standard Deviation 0.0324
Elimination Rate Constant From the Central Compartment (Kel) Glucuronide Conjugate	0.1909 1/h Standard Deviation 0.0417	0.1924 1/h Standard Deviation 0.038
Elimination Rate Constant From the Central Compartment (Kel) Unchanged edaravone	0.1194 1/h Standard Deviation 0.0876	0.1156 1/h Standard Deviation 0.0563

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Mean Residence Time From Time Zero up to Infinity With Extrapolation of the Terminal Phase (MRT0-inf) of Unchanged Edaravone	2.495 h Standard Deviation 0.903	2.333 h Standard Deviation 0.826

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Total Clearance (CL) of Unchanged Edaravone After Intravenous Administration	35.9 L/h Standard Deviation 7.5	—

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Volume of Distribution During Terminal Phase (Vz) of Unchanged Edaravone After Intravenous Administration	418 L Standard Deviation 321	—

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Volume of Distribution at Steady State (Vss) of Unchanged Edaravone After Intravenous Administration	63.1 L Standard Deviation 22.0	—

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Apparent Total Clearance (CL/F) of Unchanged Edaravone After Oral Administration	67.9 L/h Standard Deviation 30.1	—

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Unchanged Edaravone After Oral Administration	826 L Standard Deviation 618	—

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Apparent Volume of Distribution at Steady State (Vss/F) of Unchanged Edaravone After Oral Administration	164.0 L Standard Deviation 78.9	—

SECONDARY outcome

Timeframe: Urine samples are collected: Day1 to 6.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Cumulative Amount of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48) Unchanged edaravone	0.66 mg Standard Deviation 0.21	0.52 mg Standard Deviation 0.15
Cumulative Amount of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48) Sulfate conjugate	10.04 mg Standard Deviation 8.67	7.06 mg Standard Deviation 6.43
Cumulative Amount of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48) Glucuronide Conjugate	125.9 mg Standard Deviation 19.0	94.3 mg Standard Deviation 13.7

SECONDARY outcome

Timeframe: Urine samples are collected: Day1 to 6.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Cumulative Percentage of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48) Sulfate conjugate	6.58 percentage of dose Standard Deviation 5.68	8.09 percentage of dose Standard Deviation 7.37
Cumulative Percentage of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48) Glucuronide Conjugate	59.8 percentage of dose Standard Deviation 9.0	78.4 percentage of dose Standard Deviation 11.4
Cumulative Percentage of Drug Excreted in Urine From Time Zero up to 48 Hours (Ae0-48) Unchanged edaravone	0.629 percentage of dose Standard Deviation 0.199	0.869 percentage of dose Standard Deviation 0.252

SECONDARY outcome

Timeframe: Urine samples are collected: Day1 to 6.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Renal Clearance (CLr) of Unchanged Edaravone	0.424 L/h Standard Deviation 0.227	0.311 L/h Standard Deviation 0.114

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Bioavailability was calculated from ratio of AUC0-inf of unchanged edaravone after oral and intravenous administration.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Bioavailability (F) of Unchanged Edaravone After Oral Administration	57.3 percentage bioavailability Standard Deviation 12.6	—

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
AUC0-t of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration Sulfate conjugate	20031 ng·h/mL Standard Deviation 5255	15024 ng·h/mL Standard Deviation 3576
AUC0-t of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration Glucuronide Conjugate	3914 ng·h/mL Standard Deviation 730	2285 ng·h/mL Standard Deviation 481

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
AUC0-inf of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration Sulfate conjugate	20055 ng·h/mL Standard Deviation 5256	15055 ng·h/mL Standard Deviation 3579
AUC0-inf of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration Glucuronide conjugate	3924 ng·h/mL Standard Deviation 731	2295 ng·h/mL Standard Deviation 482

SECONDARY outcome

Timeframe: 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.

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Cmax of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration Sulfate conjugate	7291 ng/mL Standard Deviation 1898	4843 ng/mL Standard Deviation 817.8
Cmax of Sulfate and Glucuronide Conjugates After Oral and Intravenous Administration Glucuronide conjugate	2237 ng/mL Standard Deviation 388	1012 ng/mL Standard Deviation 235.7

SECONDARY outcome

Timeframe: Day 1 to 11

Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone oral suspension group (PO =\> IV) with 21 subjects, and the advance administration of edaravone IV formulation group (IV =\> PO) with 21 subjects to investigate the bioequivalence between edaravone oral suspension and edaravone IV formulation.

Outcome measures

Measure	Edaravone Oral Suspension n=42 Participants Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 Participants Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Number of Participants With Adverse Events and Adverse Drug Reactions Number of Participants with Adverse events	1 Participants	1 Participants
Number of Participants With Adverse Events and Adverse Drug Reactions Number of Participants with adverse drug reactions	0 Participants	0 Participants

Adverse Events

Edaravone Oral Suspension

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Edaravone IV Formulation

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Edaravone Oral Suspension n=42 participants at risk Healthy subjects were administered a single dose of Edaravone oral suspension (105 mg) under fasted condition.	Edaravone IV Formulation n=42 participants at risk Healthy subjects were administered a single dose of Edaravone IV formulation (60 mg/60 min) under fasted condition.
Gastrointestinal disorders Constipation	2.4% 1/42 • Day 1 to Day 11	0.00% 0/42 • Day 1 to Day 11
Investigations Aspartate aminotransferase increased	0.00% 0/42 • Day 1 to Day 11	2.4% 1/42 • Day 1 to Day 11

Additional Information

Clinical Trials, Information Desk

Tanabe Pharma Corporation

Phone: Please email

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

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER