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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rosuvastatin, Sildenafil, and MT-1186 | Experimental | 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. 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 MT-1186 | Experimental | Group 2 of Cohort 1: 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. |
|
| MT-1186 | Experimental | Cohort 2: 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 healthy male subjects receive a single dose of MT-1186 at the same period with Japanese subjects under the corresponding condition on Day 1, 4, or 7 according to their treatment schedule. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MT-1186 | Drug | Suspension |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Rosuvastatin, Sildenafil and Furosemide. | 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 | |
| Maximum Plasma Concentration (Cmax) of Rosuvastatin, Sildenafil and Furosemide. | 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 | |
| Tmax of Rosuvastatin, Sildenafil and Furosemide. | 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 | |
| T1/2 of Rosuvastatin, Sildenafil and Furosemide. | 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 | |
| AUC0-inf of Unchanged Edaravone. | 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. | |
| Cmax of Unchanged Edaravone. | 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. | |
| Tmax of Unchanged Edaravone. |
| Measure | Description | Time Frame |
|---|---|---|
| AUCinf of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. | 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 | |
| Cmax of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
Additional screening criteria check may apply for qualification:
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| Name | Affiliation | Role |
|---|---|---|
| General Manager | Tanabe Pharma Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational site | Tokyo | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36376130 | Result | Shimizu H, Nishimura Y, Shiide Y, Akimoto M, Matsuda H, Kato Y, Hirai M. Food Effect Study to Assess the Impact on Edaravone Pharmacokinetic Profiles in Healthy Participants. Clin Ther. 2022 Dec;44(12):1552-1565. doi: 10.1016/j.clinthera.2022.10.001. Epub 2022 Nov 12. | |
| 33704925 | Result | Shimizu H, Nishimura Y, Shiide Y, Matsuda H, Akimoto M, Matsuda M, Nakamaru Y, Kato Y, Kondo K. Evaluation of Pharmacokinetics, Safety, and Drug-Drug Interactions of an Oral Suspension of Edaravone in Healthy Adults. Clin Pharmacol Drug Dev. 2021 Oct;10(10):1174-1187. doi: 10.1002/cpdd.925. Epub 2021 Mar 11. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| Period 3 |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. MT-1186 will be administered from Day 6 to 13 with co-administration of rosuvastatin and sildenafil on Day 9 and 12, respectively. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Rosuvastatin, Sildenafil and Furosemide. | 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). | Posted | Mean | Standard Deviation | ng*h/mL | 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 |
|
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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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rosuvastatin Alone: Group 1 of Cohort 1 | Day 1 to Day 4. The subjects receive a single dose of rosuvastatin on Day 1. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 21.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials, Information Desk | Tanabe Pharma Corporation | Please e-mail | cti-inq-ml.JP@ml.tanabe-pharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 15, 2018 | May 11, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 28, 2019 | May 11, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000077553 | Edaravone |
| D000068718 | Rosuvastatin Calcium |
| D000068677 | Sildenafil Citrate |
| D005665 | Furosemide |
| ID | Term |
|---|---|
| D000983 | Antipyrine |
| D047069 | Pyrazolones |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 |
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Cohort 1 is open-label, non-randomized, sequential, and add-on study. Cohort 2 is single-dose, open-label, randomized, and cross-over study.
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| Rosuvastatin | Drug | Tablets |
|
|
| Sildenafil | Drug | Tablets |
|
|
| Furosemide | Drug | Tablets |
|
|
| 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. |
| T1/2 of Unchanged Edaravone. | 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. |
| AUC0-inf of Sulfate Conjugate. | 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. |
| Cmax of Sulfate Conjugate. | 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. |
| Tmax of Sulfate Conjugate. | 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. |
| T1/2 of Sulfate Conjugate. | 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. |
| AUC0-inf of Glucuronide Conjugate. | 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. |
| Cmax of Glucuronide Conjugate. | 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. |
| Tmax of Glucuronide Conjugate. | 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. |
| T1/2 of Glucuronide Conjugate. | 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. |
| AUC0-inf of Unchanged Edaravone. | 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 |
| Cmax of Unchanged Edaravone. | 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 |
| Tmax of Unchanged Edaravone. | 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 |
| T1/2 of Unchanged Edaravone. | 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 |
| AUCinf of Sulfate Conjugate and Glucuronide Conjugate. | 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 |
| Cmax of Sulfate Conjugate and Glucuronide Conjugate. | 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 |
| Tmax of Sulfate Conjugate and Glucuronide Conjugate. | 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 |
| T1/2 of Sulfate Conjugate and Glucuronide Conjugate. | 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 |
| T1/2 of Glucuronide Conjugate. | 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 |
| Number of Participants With Adverse Events and Adverse Drug Reactions | 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 |
| Tmax of Unchanged Edaravone. | 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 |
| T1/2 of Unchanged Edaravone. | 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 |
| COMPLETED |
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| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 |
| 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. MT-1186 will be administered from Day 3 to 7 with co-administration of furosemide on Day 6. |
| BG002 | Japanese Combined of Cohort 2 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Rosubastatin + Edaravone: Group 1 of Cohort 1 | The subjects receive edaravone from Day 6 to 13 with co-administration of rosuvastatin on Day 9. |
| OG002 | Sildenafil Alone: Group 1 of Cohort 1 | The subjects receive a single dose of sildenafil on Day 4. |
| OG003 | Sildenafil + Edaravone: Group 1 of Cohort 1 | The subjects receive edaravone from Day 6 to 13 with co-administration of sildenafil on Day 12. |
| OG004 | Furosemide Alone: Group 2 of Cohort 1 | The subjects receive a single dose of furosemide on Day 1. |
| OG005 | Furosemide + Edaravone: Group 2 of Cohort 1 | The subjects receive edaravone from Day 3 to 7 with co-administration of furosemide on Day 6. |
|
|
|
| Primary | Maximum Plasma Concentration (Cmax) of Rosuvastatin, Sildenafil and Furosemide. | 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). | Posted | Mean | Standard Deviation | ng/mL | 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 |
|
|
|
|
| Primary | Tmax of Rosuvastatin, Sildenafil and Furosemide. | 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). | Posted | Mean | Standard Deviation | h | 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 |
|
|
|
| Primary | T1/2 of Rosuvastatin, Sildenafil and Furosemide. | 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). | Posted | Mean | Standard Deviation | h | 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 |
|
|
|
| Primary | AUC0-inf of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | ng*h/mL | 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. |
|
|
|
| Primary | Cmax of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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. |
|
|
|
| Primary | Tmax of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | h | 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. |
|
|
|
| Primary | T1/2 of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | h | 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. |
|
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| Primary | AUC0-inf of Sulfate Conjugate. | 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. | Posted | Mean | Standard Deviation | ng*h/mL | 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. |
|
|
|
| Primary | Cmax of Sulfate Conjugate. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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. |
|
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| Primary | Tmax of Sulfate Conjugate. | 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. | Posted | Mean | Standard Deviation | h | 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. |
|
|
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| Primary | T1/2 of Sulfate Conjugate. | 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. | Posted | Mean | Standard Deviation | h | 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. |
|
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| Primary | AUC0-inf of Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | ng*h/mL | 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. |
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| Primary | Cmax of Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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. |
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| Primary | Tmax of Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | h | 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. |
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| Primary | T1/2 of Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | h | 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. |
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| Primary | AUC0-inf of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | ng*h/mL | 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 |
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| Primary | Cmax of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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 |
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| Primary | Tmax of Unchanged Edaravone. | 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. | Posted | Median | Full Range | h | 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 |
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| Primary | T1/2 of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | h | 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 |
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| Primary | AUCinf of Sulfate Conjugate and Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | ng*h/mL | 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 |
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| Primary | Cmax of Sulfate Conjugate and Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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 |
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| Primary | Tmax of Sulfate Conjugate and Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | h | 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 |
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| Primary | T1/2 of Sulfate Conjugate and Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | h | 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 |
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| Primary | T1/2 of Glucuronide Conjugate. | Posted | Mean | Standard Deviation | h | 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 |
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| Primary | Number of Participants With Adverse Events and Adverse Drug Reactions | 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. | Posted | Count of Participants | Participants | 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 |
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| Secondary | AUCinf of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | ng*h/mL | 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 |
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| Secondary | Cmax of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate. | 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. | Posted | Mean | Standard Deviation | ng/mL | 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 |
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| Secondary | Tmax of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | h | 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 |
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| Secondary | T1/2 of Unchanged Edaravone. | 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. | Posted | Mean | Standard Deviation | h | 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 |
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| 0 |
| 32 |
| 0 |
| 32 |
| 0 |
| 32 |
| EG001 | Sildenafil Alone: Group 1 of Cohort 1 | Day 4 to Day 5. The subjects receive a single dose of sildenafil on Day 4. | 0 | 31 | 0 | 31 | 2 | 31 |
| EG002 | Edaravone Alone: Group 1 of Cohort 1 | Day 6 to Day 8. The subjects receive a single dose of edaravone from Day 6 to Day 8. | 0 | 31 | 0 | 31 | 0 | 31 |
| EG003 | Edaravone + Rosuvastatin: Group 1 of Cohort 1 | Day 9 to Day 11. The subjects receive edaravone from Day 6 to 11 with co-administration of rosuvastatin on Day 9. | 0 | 31 | 0 | 31 | 6 | 31 |
| EG004 | Edaravone + Sildenafil: Group 1 of Cohort 1 | 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. | 0 | 31 | 0 | 31 | 3 | 31 |
| EG005 | Combined: After Day 6: Group 1 of Cohort 1 | Day 6 to Day 20 including end of study assessment. | 0 | 31 | 0 | 31 | 8 | 31 |
| EG006 | Furosemide Alone: Group 2 of Cohort 1 | Day 1 to Day 2. The subjects receive a single dose of furosemide on Day 1. | 0 | 34 | 0 | 34 | 1 | 34 |
| EG007 | 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. | 0 | 34 | 0 | 34 | 0 | 34 |
| EG008 | 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. | 0 | 34 | 0 | 34 | 7 | 34 |
| EG009 | Combined : After Day 3: Group 2 of Cohort 1 | Day 3 to Day 14 including end of study assessment. | 0 | 34 | 0 | 34 | 7 | 34 |
| EG010 | Edaravone Single Dose Under Fasting Condition: Japanese Conmibed | Japanese combined | 0 | 9 | 0 | 9 | 0 | 9 |
| EG011 | Edaravone Single Dose 1 Hour After a High-fat Meal: Japanese Conmibed | Japanese combined | 0 | 9 | 0 | 9 | 2 | 9 |
| EG012 | Edaravone Single Dose 4 Hours After a High-fat Meal: Japanese Conmibed | Japanese combined | 0 | 9 | 0 | 9 | 0 | 9 |
| EG013 | Edaravone Single Dose Under Fasting Condition: White Combined | White combined | 0 | 9 | 0 | 9 | 0 | 9 |
| Headache | Nervous system disorders | MedDRA version 21.0 | Systematic Assessment |
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| Abnormal sensation in eye | Eye disorders | MedDRA version 21.0 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA version 21.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 21.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 21.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA version 21.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA version 21.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA version 21.0 | Systematic Assessment |
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| Blood lactate dehydrogenase increased | Investigations | MedDRA version 21.0 | Systematic Assessment |
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Not provided
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D010879 | Piperazines |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| PK parameters of rosuvastatin, sildenafil, and furosemide alone and in the presence of edaravone were analyzed for the assessments of effect on PK of rosuvastatin, sildenafil, and furosemide by edaravone. | LS Mean Ratio | 0.94 | 2-Sided | 90 | 0.80 | 1.10 | Other | Estimates of least squares mean difference of log-transformed PK parameters between treatments were obtained with their 2-sided 90%CIs for the difference. These estimates and limits were then back-transformed to obtain ratios of least squares geometric means. If the 90%CIs lay entirely within the limits of 0.80 to 1.25, this would provide evidence of no effect of edaravone on the PK of rosuvastatin, sildenafil, and furosemide (LS Mean Ratio: Sildenafil + Edaravone / Sildenafil Alone). |
| PK parameters of rosuvastatin, sildenafil, and furosemide alone and in the presence of edaravone were analyzed for the assessments of effect on PK of rosuvastatin, sildenafil, and furosemide by edaravone. | LS Mean Ratio | 1.08 | 2-Sided | 90 | 0.96 | 1.23 | Other | Estimates of least squares mean difference of log-transformed PK parameters between treatments were obtained with their 2-sided 90%CIs for the difference. These estimates and limits were then back-transformed to obtain ratios of least squares geometric means. If the 90%CIs lay entirely within the limits of 0.80 to 1.25, this would provide evidence of no effect of edaravone on the PK of rosuvastatin, sildenafil, and furosemide (LS Mean Ratio: Furosemide + Edaravone / Furosemide Alone). |
| Day 6: Group 1 (Edaravpne alone), Group 2 (Edaravone + Furosemide) |
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| Day 9: Group 1 (Edaravone + Rosuvastatin), Group 2 Not Applicable |
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| Day 12: Group 1 (Edaravone + Sildenafil), Group 2 Not Applicable |
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| Day 6: Group 1 (Edaravpne alone), Group 2 (Edaravone + Furosemide) |
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| Day 9: Group 1 (Edaravone + Rosuvastatin) |
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| Day 12: Group 1 (Edaravone + Sildenafil) |
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| Day 6: Group 1 (Edaravpne alone), Group 2 (Edaravone + Furosemide) |
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| Day 9: Group 1 (Edaravone + Rosuvastatin) |
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| Day 12: Group 1 (Edaravone + Sildenafil) |
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| Day 6: Group 1 (Edaravpne alone), Group 2 (Edaravone + Furosemide) |
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| Day 9: Group 1 (Edaravone + Rosuvastatin) |
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| Day 12: Group 1 (Edaravone + Sildenafil) |
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PK parameters of unchanged edaravone were analyzed for the assessments of food effect on PK. |
| LS Mean Ratio |
| 0.737 |
| 2-Sided |
| 90 |
| 0.610 |
| 0.891 |
| Other |
Estimated difference in least squares means and corresponding 90% CI of log-transformed PK parameters were back transformed to obtain the estimate and CI of the geometric mean ratio of 4 Hours After a High-fat Meal condition to the fasted state. |
|
PK parameters of unchanged edaravone were analyzed for the assessments of food effect on PK. |
| LS Mean Ratio |
| 0.522 |
| 2-Sided |
| 90 |
| 0.301 |
| 0.903 |
| Other |
Estimated difference in least squares means and corresponding 90%CI of log-transformed PK parameters were back transformed to obtain the estimate and CI of the geometric mean ratio of 4 Hours After a High-fat Meal condition to the fasted state. |
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| Number of Participants with adverse drug reactions |
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| Glucuronide conjugate |
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| Glucuronide conjugate |
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| Glucuronide conjugate |
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| Glucuronide conjugate |
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