Trial Outcomes & Findings for Clinical Pharmacology Study of Oral Edaravone in Healthy Adult Males (Drug Interaction Study and Preliminary Regimen-Finding Study) (NCT NCT04481789)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

84 participants

Primary outcome timeframe

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

Results posted on

2026-01-07

Participant Flow

Participant milestones

Participant milestones
Measure	Rosuvastatin, Sildenafil, and Edaravone 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. Oral edaravone will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively.	Furosemide and Edaravone Group 2 of Cohort 1 A single-sequence study in which healthy male subjects receive a single dose of furosemide on Day 1. Oral edaravone will be administered from Day 3 to 7 with co-administration of furosemide on Day 6.	Edaravone Group 3 of Cohort 2 A three-way crossover study in which Japanese healthy male subjects receive a single dose of Oral edaravone under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Period 1:Japanese subjects receive a single dose of Edaravone under fasted condition on Day 1. Period 2: Japanese subjects receive a single dose of Edaravone1 hour before a high-fat meal on Day 4. Period 3: Japanese subjects receive a single dose of Edaravone 4 hours after a high-fat meal on Day 7.	Edaravone Group 4 of Cohort 2 A three-way crossover study in which Japanese healthy male subjects receive a single dose of Oral edaravone under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Period 1: Japanese subjects receive a single dose of Edaravone 4 hours after a high-fat meal. Period 2: Japanese subjects receive a single dose of Edaravone under fasted condition. Period 3: Japanese subjects receive a single dose of Edaravone1 hour before a high-fat meal.	Edaravone Group 5 of Cohort 2 A three-way crossover study in which Japanese healthy male subjects receive a single dose o Oral edaravone under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Period 1: Japanese subjects receive a single dose of Edaravone1 hour before a high-fat meal. Period 2: Japanese subjects receive a single dose of Edaravone 4 hours after a high-fat meal. Period 3: Japanese subjects receive a single dose of Edaravone under fasted condition.	Caucasian Group of Cohort 2 Caucasian healthy male subjects receive a single dose of MT-1186 under fasted condition at the same period with Japanese subjects on Day 1, 4, or 7 according to their treatment schedule.
Period 1 STARTED	32	34	3	3	3	3
Period 1 COMPLETED	31	34	3	3	3	3
Period 1 NOT COMPLETED	1	0	0	0	0	0
Period 2 STARTED	31	34	3	3	3	3
Period 2 COMPLETED	31	34	3	3	3	3
Period 2 NOT COMPLETED	0	0	0	0	0	0
Period 3 STARTED	31	0	3	3	3	3
Period 3 COMPLETED	31	0	3	3	3	3
Period 3 NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Rosuvastatin, Sildenafil, and Edaravone 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. Oral edaravone will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively.	Furosemide and Edaravone Group 2 of Cohort 1 A single-sequence study in which healthy male subjects receive a single dose of furosemide on Day 1. Oral edaravone will be administered from Day 3 to 7 with co-administration of furosemide on Day 6.	Edaravone Group 3 of Cohort 2 A three-way crossover study in which Japanese healthy male subjects receive a single dose of Oral edaravone under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Period 1:Japanese subjects receive a single dose of Edaravone under fasted condition on Day 1. Period 2: Japanese subjects receive a single dose of Edaravone1 hour before a high-fat meal on Day 4. Period 3: Japanese subjects receive a single dose of Edaravone 4 hours after a high-fat meal on Day 7.	Edaravone Group 4 of Cohort 2 A three-way crossover study in which Japanese healthy male subjects receive a single dose of Oral edaravone under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Period 1: Japanese subjects receive a single dose of Edaravone 4 hours after a high-fat meal. Period 2: Japanese subjects receive a single dose of Edaravone under fasted condition. Period 3: Japanese subjects receive a single dose of Edaravone1 hour before a high-fat meal.	Edaravone Group 5 of Cohort 2 A three-way crossover study in which Japanese healthy male subjects receive a single dose o Oral edaravone under several dosing condition on Day 1, 4, and 7 according to their treatment sequence with 3-day wash out between doses. Period 1: Japanese subjects receive a single dose of Edaravone1 hour before a high-fat meal. Period 2: Japanese subjects receive a single dose of Edaravone 4 hours after a high-fat meal. Period 3: Japanese subjects receive a single dose of Edaravone under fasted condition.	Caucasian Group of Cohort 2 Caucasian healthy male subjects receive a single dose of MT-1186 under fasted condition at the same period with Japanese subjects on Day 1, 4, or 7 according to their treatment schedule.
Period 1 Withdrawal by Subject	1	0	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rosuvastatin, Sildenafil, and Edaravone Group 1 of Cohort 1 n=32 Participants 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.	Furosemide and Edaravone Group 2 of Cohort 1 n=34 Participants 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.	Japanese Combined of Cohort 2 n=9 Participants 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 Group of Cohort 2 n=9 Participants Caucasian healthy male subjects receive a single dose of MT-1186 under fasted condition at the same period with Japanese subjects on Day 1, 4, or 7 according to their treatment schedule.	Total n=84 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	0 Participants n=61 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	32 Participants n=37 Participants	34 Participants n=56 Participants	9 Participants n=95 Participants	9 Participants n=61 Participants	84 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants	0 Participants n=61 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants	0 Participants n=61 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=37 Participants	34 Participants n=56 Participants	9 Participants n=95 Participants	9 Participants n=61 Participants	84 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants	0 Participants n=61 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	32 Participants n=37 Participants	34 Participants n=56 Participants	9 Participants n=95 Participants	0 Participants n=61 Participants	75 Participants n=5 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	0 Participants n=61 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants	0 Participants n=61 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants	9 Participants n=61 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants	0 Participants n=61 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	0 Participants n=56 Participants	0 Participants n=95 Participants	0 Participants n=61 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2).

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=32 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 n=34 Participants The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 n=34 Participants The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Rosuvastatin, Sildenafil and Furosemide.	161 ng*h/mL Standard Deviation 66.8	165 ng*h/mL Standard Deviation 60.2	532 ng*h/mL Standard Deviation 236	482 ng*h/mL Standard Deviation 195	3861 ng*h/mL Standard Deviation 1031	3906 ng*h/mL Standard Deviation 736.2	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2).

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=32 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 n=34 Participants The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 n=34 Participants The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Maximum Plasma Concentration (Cmax) of Rosuvastatin, Sildenafil and Furosemide.	11.3 ng/mL Standard Deviation 5.0	11.3 ng/mL Standard Deviation 5.0	232 ng/mL Standard Deviation 135	201 ng/mL Standard Deviation 97.9	1676 ng/mL Standard Deviation 777.7	1701 ng/mL Standard Deviation 506.5	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2).

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=32 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 n=34 Participants The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 n=34 Participants The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Tmax of Rosuvastatin, Sildenafil and Furosemide.	4.6 h Standard Deviation 1.5	5.1 h Standard Deviation 1.4	0.8 h Standard Deviation 0.4	0.9 h Standard Deviation 0.5	1.7 h Standard Deviation 1.1	1.8 h Standard Deviation 1.1	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2).

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=32 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 n=34 Participants The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 n=34 Participants The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
T1/2 of Rosuvastatin, Sildenafil and Furosemide.	14.4 h Standard Deviation 4.0	12.1 h Standard Deviation 2.2	2.8 h Standard Deviation 1.1	3.5 h Standard Deviation 1.4	6.9 h Standard Deviation 3.5	5.8 h Standard Deviation 3.8	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Day 3 of Group 1 and Day 9 and 12 of Group 2 were zero participant because no data was collected.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=34 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
AUC0-inf of Unchanged Edaravone. Day 9: Group 1 (Edaravone + Rosuvastatin), Group 2 Not Applicable	2591 ng*h/mL Standard Deviation 671	—	—	—	—	—	—	—	—	—	—	—	—	—
AUC0-inf of Unchanged Edaravone. Day 12: Group 1 (Edaravone + Sildenafil), Group 2 Not Applicable	2656 ng*h/mL Standard Deviation 712	—	—	—	—	—	—	—	—	—	—	—	—	—
AUC0-inf of Unchanged Edaravone. Day 3: Group 2 (Edaravone alone)	—	2535 ng*h/mL Standard Deviation 919	—	—	—	—	—	—	—	—	—	—	—	—
AUC0-inf of Unchanged Edaravone. Day 6: Group 1 (Edaravpne alone), Group 2 (Edaravone + Furosemide)	2616 ng*h/mL Standard Deviation 730	2746 ng*h/mL Standard Deviation 1015	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Day 3 of Group 1 and Day 9 and 12 of Group 2 were zero participant because no data was collected.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=34 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Cmax of Unchanged Edaravone. Day 6: Group 1 (Edaravpne alone), Group 2 (Edaravone + Furosemide)	2724 ng/mL Standard Deviation 1533	2074 ng/mL Standard Deviation 1051	—	—	—	—	—	—	—	—	—	—	—	—
Cmax of Unchanged Edaravone. Day 9: Group 1 (Edaravone + Rosuvastatin)	2302 ng/mL Standard Deviation 943	—	—	—	—	—	—	—	—	—	—	—	—	—
Cmax of Unchanged Edaravone. Day 12: Group 1 (Edaravone + Sildenafil)	2455 ng/mL Standard Deviation 1111	—	—	—	—	—	—	—	—	—	—	—	—	—
Cmax of Unchanged Edaravone. Day 3: Group 2 (Edaravone alone)	—	2180 ng/mL Standard Deviation 1035	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Day 3 of Group 1 and Day 9 and 12 of Group 2 were zero participants because no data was collected.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=34 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Tmax of Unchanged Edaravone. Day 3: Group 2 (Edaravone alone)	—	0.34 h Standard Deviation 0.19	—	—	—	—	—	—	—	—	—	—	—	—
Tmax of Unchanged Edaravone. Day 6: Group 1 (Edaravpne alone), Group 2 (Edaravone + Furosemide)	0.30 h Standard Deviation 0.10	0.34 h Standard Deviation 0.17	—	—	—	—	—	—	—	—	—	—	—	—
Tmax of Unchanged Edaravone. Day 9: Group 1 (Edaravone + Rosuvastatin)	0.34 h Standard Deviation 0.13	—	—	—	—	—	—	—	—	—	—	—	—	—
Tmax of Unchanged Edaravone. Day 12: Group 1 (Edaravone + Sildenafil)	0.32 h Standard Deviation 0.17	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Day 3 of Group 1 and Day 9 and 12 of Group 2 were zero participants because no data was collected.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=34 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
T1/2 of Unchanged Edaravone. Day 6: Group 1 (Edaravpne alone), Group 2 (Edaravone + Furosemide)	5.23 h Standard Deviation 1.11	5.52 h Standard Deviation 0.60	—	—	—	—	—	—	—	—	—	—	—	—
T1/2 of Unchanged Edaravone. Day 9: Group 1 (Edaravone + Rosuvastatin)	6.60 h Standard Deviation 1.18	—	—	—	—	—	—	—	—	—	—	—	—	—
T1/2 of Unchanged Edaravone. Day 12: Group 1 (Edaravone + Sildenafil)	6.69 h Standard Deviation 1.31	—	—	—	—	—	—	—	—	—	—	—	—	—
T1/2 of Unchanged Edaravone. Day 3: Group 2 (Edaravone alone)	—	4.67 h Standard Deviation 0.92	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Sulfate and glucuronide conjugates were not measured in Cohort 1 Group 1.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=34 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
AUC0-inf of Sulfate Conjugate. Day 3: Group 2 (Edaravone alone)	26576 ng*h/mL Standard Deviation 6820	—	—	—	—	—	—	—	—	—	—	—	—	—
AUC0-inf of Sulfate Conjugate. Day 6: Group 2 (Edaravone + Furosemide)	30588 ng*h/mL Standard Deviation 7064	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Sulfate and glucuronide conjugates were not measured in Cohort 1 Group 1.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=34 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Cmax of Sulfate Conjugate. Day 3: Group 2 (Edaravone alone)	8115 ng/mL Standard Deviation 1775	—	—	—	—	—	—	—	—	—	—	—	—	—
Cmax of Sulfate Conjugate. Day 6: Group 2 (Edaravone + Furosemide)	8702 ng/mL Standard Deviation 2147	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Sulfate and glucuronide conjugates were not measured in Cohort 1 Group 1.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=34 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Tmax of Sulfate Conjugate. Day 3: Group 2 (Edaravone alone)	0.76 h Standard Deviation 0.28	—	—	—	—	—	—	—	—	—	—	—	—	—
Tmax of Sulfate Conjugate. Day 6: Group 2 (Edaravone + Furosemide)	0.81 h Standard Deviation 0.30	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Sulfate and glucuronide conjugates were not measured in Cohort 1 Group 1.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=34 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
T1/2 of Sulfate Conjugate. Day 3: Group 2 (Edaravone alone)	3.89 h Standard Deviation 0.25	—	—	—	—	—	—	—	—	—	—	—	—	—
T1/2 of Sulfate Conjugate. Day 6: Group 2 (Edaravone + Furosemide)	4.20 h Standard Deviation 0.33	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Sulfate and glucuronide conjugates were not measured in Cohort 1 Group 1.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=34 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
AUC0-inf of Glucuronide Conjugate. Day 6: Group 2 (Edaravone + Furosemide)	4953 ng*h/mL Standard Deviation 1285	—	—	—	—	—	—	—	—	—	—	—	—	—
AUC0-inf of Glucuronide Conjugate. Day 3: Group 2 (Edaravone alone)	4817 ng*h/mL Standard Deviation 1282	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Sulfate and glucuronide conjugates were not measured in Cohort 1 Group 1.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=34 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Cmax of Glucuronide Conjugate. Day 3: Group 2 (Edaravone alone)	2318 ng/mL Standard Deviation 649	—	—	—	—	—	—	—	—	—	—	—	—	—
Cmax of Glucuronide Conjugate. Day 6: Group 2 (Edaravone + Furosemide)	2304 ng/mL Standard Deviation 694	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Sulfate and glucuronide conjugates were not measured in Cohort 1 Group 1.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=34 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Tmax of Glucuronide Conjugate. Day 6: Group 2 (Edaravone + Furosemide)	0.57 h Standard Deviation 0.18	—	—	—	—	—	—	—	—	—	—	—	—	—
Tmax of Glucuronide Conjugate. Day 3: Group 2 (Edaravone alone)	0.61 h Standard Deviation 0.26	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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.

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Sulfate and glucuronide conjugates were not measured in Cohort 1 Group 1.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=34 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
T1/2 of Glucuronide Conjugate. Day 3: Group 2 (Edaravone alone)	3.65 h Standard Deviation 0.28	—	—	—	—	—	—	—	—	—	—	—	—	—
T1/2 of Glucuronide Conjugate. Day 6: Group 2 (Edaravone + Furosemide)	3.97 h Standard Deviation 0.31	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
AUC0-inf of Unchanged Edaravone.	1647 ng*h/mL Standard Deviation 433	1475 ng*h/mL Standard Deviation 658	1247 ng*h/mL Standard Deviation 425	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Cmax of Unchanged Edaravone.	1810 ng/mL Standard Deviation 849.8	1502 ng/mL Standard Deviation 1272	1012 ng/mL Standard Deviation 603.3	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Tmax of Unchanged Edaravone.	0.25 h Interval 0.25 to 1.0	0.50 h Interval 0.25 to 1.5	0.25 h Interval 0.25 to 1.0	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
T1/2 of Unchanged Edaravone.	9.33 h Standard Deviation 4.87	9.65 h Standard Deviation 5.41	7.66 h Standard Deviation 4.12	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
AUCinf of Sulfate Conjugate and Glucuronide Conjugate. Sulfate conjugate	24484 ng*h/mL Standard Deviation 5861	22689 ng*h/mL Standard Deviation 6334	23022 ng*h/mL Standard Deviation 5094	—	—	—	—	—	—	—	—	—	—	—
AUCinf of Sulfate Conjugate and Glucuronide Conjugate. Glucuronide conjugate	4178 ng*h/mL Standard Deviation 873	4099 ng*h/mL Standard Deviation 637	3557 ng*h/mL Standard Deviation 879	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Cmax of Sulfate Conjugate and Glucuronide Conjugate. Sulfate conjugate	8394 ng/mL Standard Deviation 1609	7802 ng/mL Standard Deviation 1556	8152 ng/mL Standard Deviation 1731	—	—	—	—	—	—	—	—	—	—	—
Cmax of Sulfate Conjugate and Glucuronide Conjugate. Glucuronide conjugate	2391 ng/mL Standard Deviation 508	2176 ng/mL Standard Deviation 475	1924 ng/mL Standard Deviation 380	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Tmax of Sulfate Conjugate and Glucuronide Conjugate. Sulfate conjugate	0.67 h Standard Deviation 0.25	0.91 h Standard Deviation 0.39	0.72 h Standard Deviation 0.26	—	—	—	—	—	—	—	—	—	—	—
Tmax of Sulfate Conjugate and Glucuronide Conjugate. Glucuronide conjugate	0.53 h Standard Deviation 0.20	0.76 h Standard Deviation 0.35	0.72 h Standard Deviation 0.26	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
T1/2 of Sulfate Conjugate and Glucuronide Conjugate. Glucuronide conjugate	4.26 h Standard Deviation 0.38	3.89 h Standard Deviation 0.79	3.88 h Standard Deviation 0.55	—	—	—	—	—	—	—	—	—	—	—
T1/2 of Sulfate Conjugate and Glucuronide Conjugate. Sulfate conjugate	10.50 h Standard Deviation 7.67	7.53 h Standard Deviation 3.55	7.55 h Standard Deviation 2.47	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
T1/2 of Glucuronide Conjugate.	4.26 h Standard Deviation 0.38	4.35 h Standard Deviation 0.25	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=32 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 n=31 Participants The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 n=31 Participants The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 n=31 Participants The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 n=34 Participants Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 n=34 Participants Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 n=34 Participants Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 n=34 Participants Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed n=9 Participants Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed n=9 Participants Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed n=9 Participants Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined n=9 Participants White combined
Number of Participants With Adverse Events and Adverse Drug Reactions Number of Participants with Adverse events	0 Participants	2 Participants	0 Participants	6 Participants	3 Participants	8 Participants	1 Participants	0 Participants	7 Participants	7 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events and Adverse Drug Reactions Number of Participants with adverse drug reactions	0 Participants	0 Participants	0 Participants	5 Participants	0 Participants	5 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. 18 subjects (9 Japanese and 9 White) were enrolled in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
AUCinf of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. Unchanged edaravone	1647 ng*h/mL Standard Deviation 433	1423 ng*h/mL Standard Deviation 391	—	—	—	—	—	—	—	—	—	—	—	—
AUCinf of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. Sulfate conjugate	24484 ng*h/mL Standard Deviation 5861	20098 ng*h/mL Standard Deviation 1592	—	—	—	—	—	—	—	—	—	—	—	—
AUCinf of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. Glucuronide conjugate	4178 ng*h/mL Standard Deviation 873	3795 ng*h/mL Standard Deviation 571	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. 18 subjects (9 Japanese and 9 White) were enrolled in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Cmax of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. Sulfate conjugate	8394 ng/mL Standard Deviation 1609	6530 ng/mL Standard Deviation 787	—	—	—	—	—	—	—	—	—	—	—	—
Cmax of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. Glucuronide conjugate	2391 ng/mL Standard Deviation 508	2136 ng/mL Standard Deviation 403	—	—	—	—	—	—	—	—	—	—	—	—
Cmax of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. Unchanged edaravone	1810 ng/mL Standard Deviation 850	1484 ng/mL Standard Deviation 920	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. 18 subjects (9 Japanese and 9 White) were enrolled in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
Tmax of Unchanged Edaravone. Glucuronide conjugate	0.53 h Standard Deviation 0.20	0.61 h Standard Deviation 0.22	—	—	—	—	—	—	—	—	—	—	—	—
Tmax of Unchanged Edaravone. Unchanged edaravone	0.4 h Standard Deviation 0.3	0.4 h Standard Deviation 0.2	—	—	—	—	—	—	—	—	—	—	—	—
Tmax of Unchanged Edaravone. Sulfate conjugate	0.67 h Standard Deviation 0.25	0.67 h Standard Deviation 0.25	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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

Population: This study was conducted in 2 cohorts; the first cohort assessed DDIs with multiple doses of oral edaravone, and the second cohort evaluated PK and racial differences in PK parameters with oral administration of edaravone. 18 subjects (9 Japanese and 9 White) were enrolled in Cohort 2.

Outcome measures

Outcome measures
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=9 Participants The subjects receive a single dose of rosuvastatin on Day 1.	Rosubastatin + Edaravone: Group 1 of Cohort 1 n=9 Participants The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9.	Sildenafil Alone: Group 1 of Cohort 1 The subjects receive a single dose of sildenafil on Day 4.	Sildenafil + Edaravone: Group 1 of Cohort 1 The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12.	Furosemide Alone: Group 2 of Cohort 1 The subjects receive a single dose of furosemide on Day 1.	Furosemide + Edaravone: Group 2 of Cohort 1 The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6.	Furosemide Alone: Group 2 of Cohort 1 Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed Japanese combined	Edaravone Single Dose Under Fasting Condition: White Conbined White combined
T1/2 of Unchanged Edaravone. Unchanged edaravone	9.3 h Standard Deviation 4.9	16.2 h Standard Deviation 15.8	—	—	—	—	—	—	—	—	—	—	—	—
T1/2 of Unchanged Edaravone. Sulfate conjugate	10.5 h Standard Deviation 7.7	10.7 h Standard Deviation 6.5	—	—	—	—	—	—	—	—	—	—	—	—
T1/2 of Unchanged Edaravone. Glucuronide conjugate	4.3 h Standard Deviation 0.4	4.4 h Standard Deviation 0.3	—	—	—	—	—	—	—	—	—	—	—	—

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Rosuvastatin Alone: Group 1 of Cohort 1 n=32 participants at risk Day 1 to Day 4. The subjects receive a single dose of rosuvastatin on Day 1.	Sildenafil Alone: Group 1 of Cohort 1 n=31 participants at risk Day 4 to Day 5. The subjects receive a single dose of sildenafil on Day 4.	Edaravone Alone: Group 1 of Cohort 1 n=31 participants at risk Day 6 to Day 8. The subjects receive a single dose of edaravone from Day 6 to Day 8.	Edaravone + Rosuvastatin: Group 1 of Cohort 1 n=31 participants at risk Day 9 to Day 11. The subjects receive edaravone from Day 6 to 11 with co-administration of rosuvastatin on Day 9.	Edaravone + Sildenafil: Group 1 of Cohort 1 n=31 participants at risk Day 12 to Day 20 including end of study assessment. The subjects receive edaravone from Day 12 and 13 with co-administration of sildenafil on Day 12.	Combined: After Day 6: Group 1 of Cohort 1 n=31 participants at risk Day 6 to Day 20 including end of study assessment.	Furosemide Alone: Group 2 of Cohort 1 n=34 participants at risk Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1.	Edaravone Alone: Group 2 of Cohort 1 n=34 participants at risk Day 3 to Day 5. The subjects receive a single dose of edaravone from Day 3 to Day 5.	Edaravone + Furosemide: Group 2 of Cohort 1 n=34 participants at risk Day 6 to Day 14 including end of study assessment. The subjects receive edaravone on Day 6 to Day 7 with co-administration of furosemide on Day 6.	Combined : After Day 3: Group 2 of Cohort 1 n=34 participants at risk Day 3 to Day 14 including end of study assessment.	Edaravone Single Dose Under Fasting Condition: Japanese Conmibed n=9 participants at risk Japanese combined	Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed n=9 participants at risk Japanese combined	Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed n=9 participants at risk Japanese combined	Edaravone Single Dose Under Fasting Condition: White Combined n=9 participants at risk White combined
Blood and lymphatic system disorders Anaemia	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	14.7% 5/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	14.7% 5/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Nervous system disorders Headache	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	6.5% 2/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	2.9% 1/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	8.8% 3/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	8.8% 3/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Eye disorders Abnormal sensation in eye	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	3.2% 1/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	3.2% 1/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Cardiac disorders Palpitations	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	3.2% 1/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	3.2% 1/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	3.2% 1/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Gastrointestinal disorders Diarrhoea	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	12.9% 4/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	12.9% 4/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Investigations Alanine aminotransferase increased	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	3.2% 1/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	6.5% 2/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	9.7% 3/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	22.2% 2/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Investigations Aspartate aminotransferase increased	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	3.2% 1/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	3.2% 1/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	11.1% 1/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Investigations Blood creatine phosphokinase increased	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	11.1% 1/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.
Investigations Blood lactate dehydrogenase increased	0.00% 0/32 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/31 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/34 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	11.1% 1/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.	0.00% 0/9 • Cohort 1 Group 1: Day 1 to Day 20. Cohort 1 Group 2 and Cohort 2: Day 1 to Day 14. This study was conducted in 2 cohorts; the first cohort assessed DDIs, and the second cohort evaluated PK and racial differences in PK parameters with oral edaravone. DDI effects of oral edaravone was evaluated based on the number of subjects in each period in Cohort 1 (Group 1: Period 1 to 3, Group 2: Period 1 and 2). Three groups of randomized Japanese subjects received a single dose of edaravone under each of 3 dosing meal conditions in a 3-way, 3-period crossover fashion (3X3) in Cohort 2.

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