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To evaluate the effect of food on the pharmacokinetics of oral edaravone in healthy adult subjects. In this study, we determined 5 different dietary conditions including 4 different meal contents and fasting condition.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | A single oral dose of MT-1186 with fasted condition in period 1, meal 1 condition in period 2, meal 2 condition in period 3, meal 3 condition in period 4, and meal 4 condition in period 5. |
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| Group B | Experimental | A single oral dose of MT-1186 with meal 1 condition in period 1, meal 2 condition in period 2, meal 3 condition in period 3, fasted condition in period 4, and meal 4 condition in period 5. |
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| Group C | Experimental | A single oral dose of MT-1186 with meal 2 condition in period 1, meal 3 condition in period 2, fasted condition in period 3, meal 1 condition in period 4, and meal 4 condition in period 5. |
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| Group D | Experimental | A single oral dose of MT-1186 with meal 3 condition in period 1, fasted condition in period 2, meal 1 condition in period 3, meal 2 in period 4, and meal 4 condition in period 5. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MT-1186 | Drug | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration Versus Time Curve From Zero up to Infinity (AUC0-inf) of Edaravone | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration | |
| Maximum Plasma Concentration (Cmax) of Edaravone | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration | |
| AUC0-inf of Sulfate Conjugate and Glucuronide Conjugate | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration | |
| Cmax of Sulfate Conjugate and Glucuronide Conjugate | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration | |
| Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration | |
| Terminal Elimination Half-life (t1/2) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration | |
| Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration | |
| Mean Residence Time (MRT) of Unchanged Edaravone |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events and Adverse Drug Reactions | Day 1 to Day 31 |
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Inclusion Criteria:
Subjects who meet all of the following criteria and who have the capability of giving informed consent will be included in the study.
Exclusion Criteria:
Subjects who met any of the following exclusion criteria between screening and investigational product administration were excluded from the study:
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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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. MT-1186 orally dosing under fasted condition in period 1, dosing 8 hours after high-fat meal in period 2, dosing 4 hours after low-fat meal in period 3, dosing 2 hours after light meal in period 4, and dosing 2 hours after low-fat meal in period 5. |
| FG001 | Group B | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. MT-1186 orally dosing 8 hours after high-fat meal in period 1, dosing 4 hours after low-fat meal in period 2, dosing 2 hours after light meal in period 3, dosing under fasted condition in period 4 and dosing 2 hours after low-fat meal in period 5. |
| FG002 | Group C | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. MT-1186 orally dosing 4 hours after low-fat meal in period 1, dosing 2 hours after light meal in period 2, dosing under fasted condition in period 3, dosing 8 hours after high-fat meal in period 4 and dosing 2 hours after low-fat meal in period 5. |
| FG003 | Group D | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. MT-1186 orally dosing 2 hours after light meal in period 1, dosing under fasted condition in period 2, dosing 8 hours after high-fat meal in period 3, dosing 4 hours after low-fat meal in period 4 and dosing 2 hours after low-fat meal in period 5. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| Period 3 |
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| Period 4 |
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| Period 5 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. MT-1186 orally dosing under fasted condition in period 1, dosing 8 hours after high-fat meal in period 2, dosing 4 hours after low-fat meal in period 3, dosing 2 hours after light meal in period 4, and dosing 2 hours after low-fat meal in period 5. |
| Units | Counts |
|---|---|
| Participants |
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| 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 Zero up to Infinity (AUC0-inf) of Edaravone | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | ng·h/mL | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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Day 1 to Day 31
Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition).
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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 | Edaravone Single Dose Under Fasting Condition | Subjects receive the edaravone oral suspension orally. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA version 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials, Information Desk | Tanabe Pharma Corporation | Please email | 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 | May 13, 2019 | Mar 29, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 28, 2019 | Mar 29, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000077553 | Edaravone |
| ID | Term |
|---|---|
| D000983 | Antipyrine |
| D047069 | Pyrazolones |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 |
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| Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
| Apparent Total Clearance (CL/F) of Unchanged Edaravone | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
| Apparent Distribution Volume at Elimination Phase (Vz/F) of Unchanged Edaravone | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
| Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
| Cumulative Urinary Excretion Amount (Ae 0-24h) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Day 1 to 9, Day 24 to 26 |
| Urinary Excretion Ratio (Ae% 0-24h) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Day 1 to 9, Day 24 to 26 |
| Renal Clearance (CLr) of Unchanged Edaravone | Day 1 to 9, Day 24 to 26 |
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| NOT COMPLETED |
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| COMPLETED |
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| COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG001 | Group B | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. MT-1186 orally dosing 8 hours after high-fat meal in period 1, dosing 4 hours after low-fat meal in period 2, dosing 2 hours after light meal in period 3, dosing under fasted condition in period 4 and dosing 2 hours after low-fat meal in period 5. |
| BG002 | Group C | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. MT-1186 orally dosing 4 hours after low-fat meal in period 1, dosing 2 hours after light meal in period 2, dosing under fasted condition in period 3, dosing 8 hours after high-fat meal in period 4 and dosing 2 hours after low-fat meal in period 5. |
| BG003 | Group D | A crossover study in which Japanese healthy subjects receive a single dose of MT-1186 under several dosing condition on Day 1, 3, 5, 7 and 24 according to their treatment sequence. MT-1186 orally dosing 2 hours after light meal in period 1, dosing under fasted condition in period 2, dosing 8 hours after high-fat meal in period 3, dosing 4 hours after low-fat meal in period 4 and dosing 2 hours after low-fat meal in period 5. |
| BG004 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| OG002 | Edaravone Single Dose 4 Hours After a Low-fat Meal | Subjects receive the edaravone oral suspension orally. |
| OG003 | Edaravone Single Dose 2 Hours After a Light Meal | Subjects receive the edaravone oral suspension orally. |
| OG004 | Edaravone Single Dose 2 Hours After a Low-fat Meal | Subjects receive the edaravone oral suspension orally. |
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| Primary | Maximum Plasma Concentration (Cmax) of Edaravone | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | ng/mL | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | AUC0-inf of Sulfate Conjugate and Glucuronide Conjugate | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | ng·h/mL | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Cmax of Sulfate Conjugate and Glucuronide Conjugate | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | ng/mL | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Median | Full Range | h | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | h | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | 1/h | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Mean Residence Time (MRT) of Unchanged Edaravone | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | h | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Apparent Total Clearance (CL/F) of Unchanged Edaravone | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | L/h | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Apparent Distribution Volume at Elimination Phase (Vz/F) of Unchanged Edaravone | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | L | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | L | Before administration, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24, 36 and 48 hours after administration |
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| Primary | Cumulative Urinary Excretion Amount (Ae 0-24h) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | mg | Day 1 to 9, Day 24 to 26 |
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| Primary | Urinary Excretion Ratio (Ae% 0-24h) of Unchanged Edaravone, Sulfate Conjugate and Glucuronide Conjugate | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | % of dose | Day 1 to 9, Day 24 to 26 |
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| Primary | Renal Clearance (CLr) of Unchanged Edaravone | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Mean | Standard Deviation | L/h | Day 1 to 9, Day 24 to 26 |
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| Secondary | Number of Participants With Adverse Events and Adverse Drug Reactions | Four groups of randomized participants received edaravone oral suspension under 5 dosing conditions (4 subjects per group, 16 subjects per dosing condition). | Posted | Count of Participants | Participants | Day 1 to Day 31 |
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| 0 |
| 16 |
| 0 |
| 16 |
| 0 |
| 16 |
| EG001 | Edaravone Single Dose 8 Hours After a High-fat Meal | Subjects receive the edaravone oral suspension orally. | 0 | 16 | 0 | 16 | 0 | 16 |
| EG002 | Edaravone Single Dose 4 Hours After a Low-fat Meal | Subjects receive the edaravone oral suspension orally. | 0 | 16 | 0 | 16 | 1 | 16 |
| EG003 | Edaravone Single Dose 2 Hours After a Light Meal | Subjects receive the edaravone oral suspension orally. | 0 | 16 | 0 | 16 | 0 | 16 |
| EG004 | Edaravone Single Dose 2 Hours After a Low-fat Meal | Subjects receive the edaravone oral suspension orally. | 0 | 16 | 0 | 16 | 0 | 16 |
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| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
PK parameters of unchanged edaravone were analyzed for the assessments of food effect on PK. |
| ANOVA |
| LS Mean Ratio |
| 0.872 |
| 2-Sided |
| 90 |
| 0.661 |
| 1.150 |
| 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 each meal condition to the fasted state. |
| PK parameters of unchanged edaravone were analyzed for the assessments of food effect on PK. | ANOVA | LS Mean Ratio | 0.820 | 2-Sided | 90 | 0.621 | 1.082 | 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 each meal condition to the fasted state. |
| PK parameters of unchanged edaravone were analyzed for the assessments of food effect on PK. | ANOVA | LS Mean Ratio | 0.536 | 2-Sided | 90 | 0.362 | 0.794 | 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 each meal condition to the fasted state. |
| Glucuronide conjugate |
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| Glucuronide conjugate |
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| Sulfate conjugate |
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| Glucuronide conjugate |
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| Sulfate conjugate |
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| Glucuronide conjugate |
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| Sulfate conjugate |
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| Glucuronide conjugate |
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| Sulfate conjugate |
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| Glucuronide conjugate |
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| Sulfate conjugate |
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| Glucuronide conjugate |
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| Number of Participants with adverse drug reactions |
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