Healthy Adult Subjects
Conditions
Brief summary
To investigate the comparative bioavailability of edaravone oral suspension administered orally and via a nasogastric tube in healthy adult subjects
Interventions
DRUGMT-1186
Suspension
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 45 Years
Healthy volunteers
Yes
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. 1. Healthy adult male or female volunteers 2. Japanese 3. Subjects aged between 20 and 45 years at the time of informed consent 4. Subjects who have thoroughly understood the contents of the study and voluntarily provided written informed consent to participate in the study
Exclusion criteria
Subjects who meet any of the following criteria between screening and investigational product administration will be excluded from the study. 1. Subjects with a current or previous history of cardiac, hepatic, renal, gastrointestinal, respiratory, psychiatric/nervous, hematopoietic, or endocrine diseases, and those whom the investigator (or subinvestigator) deems unsuitable for the study 2. History of drug or food allergies 3. History of alcohol or drug abuse or dependence 4. Body mass index (BMI) of \<18.0 or \>30.0, or a body weight of \<50 kg (BMI formula: body weight \[kg\]/height \[m\]2, rounded to one decimal place) 5. Positive test for any of the following at screening: Hepatitis B surface antigen, serological test for syphilis, hepatitis C virus antibody, or human immunodeficiency virus antigen/antibody, subject has a positive COVID-19 virus test on Day -1 6. Any clinically significant 12-lead ECG abnormality or QTcF interval ≥450 msec 7. Blood donation or sampling with a total volume of ≥400 mL within 12 weeks, ≥200 mL within 4 weeks, or ≥800 mL within one year before providing informed consent 8. Blood component donation or blood sampling within 2 weeks before providing informed consent, or blood donation and transfusion from informed consent to the start of investigational product administration 9. Subjects who have undergone any surgery known to affect the gastrointestinal absorption of drugs (except for appendectomy and herniotomy) 10. Female subjects of childbearing potential who do not agree to use an effective method of contraception from screening or 2 weeks before the start of investigational product administration, whichever comes earlier, to 14 days after the completion (or discontinuation) of investigational product administration. Male subjects who do not agree to use an effective method of contraception from the start of investigational product administration to 14 days after the completion (or discontinuation) of investigational product administration 11. Subjects who have previously received edaravone 12. Subjects who have participated in another clinical study and received an investigational product within 12 weeks before providing informed consent 13. Subjects who have used any drugs other than the single use of acetylsalicylic acid within 7 days before the initiation of investigational product administration 14. Use of alcohol or any products containing xanthin or caffeine within 24 hours before screening and visit on Day -1 15. Use of any nutritional supplement(s) within 7 days before the initiation of investigational product administration 16. Use of grapefruit, grapefruit juice, or any processed food(s) containing these substances within 24 hours before screening and visit on Day -1 17. Use of any tobacco or nicotine-containing product(s) within 24 hours before screening and visit on Day -1 18. Female subjects who have a positive pregnancy test at screening and on Day -1, are pregnant or breast feeding, or plan to get pregnant during the study 19. Subjects with a history of reconstructive nasal surgery, or any evidence of deformities or asymmetry of the nose, non-patent nares/obstructed nasal airway, or the presence of nasal ulcers or polyps that would prevent an adequate NGT insertion. 20. Subjects judged by the investigator (or subinvestigator) to be unsuitable for the study for any other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Versus Time Curve (AUC) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hours after administration. | Area under the plasma concentration versus time curve from time zero up to the last quantifiable concentration time-point (AUC0-t) of edaravone, and Area under the plasma concentration versus time curve from time zero up to infinity with extrapolation of the terminal phase (AUC0-inf) of edaravone. |
| Maximum Plasma Concentration (Cmax) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration. | — |
| Time to Reach Maximum Plasma Concentration (Tmax) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration. | — |
| Terminal Elimination Half-life (t1/2) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration. | — |
| Apparent Terminal Elimination Rate Constant (Kel) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration. | — |
| Mean Residence Time (MRT) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration. | — |
| Apparent Total Clearance (CL/F) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration. | — |
| Apparent Distribution Volume at Elimination Phase (Vz/F) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration. | — |
| Apparent Distribution Volume at Steady State (Vss/F) of Edaravone | Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events and Adverse Drug Reactions | Day 1 to 11 |
Countries
Japan
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MT-1186 Orally, Then MT-1186 Via a Nasogastric Tube (NGT) Period 1: a single dose of Edaravone oral suspension orally. Period 2: a single dose of Edaravone oral suspension via a NGT. | 18 |
| MT-1186 Via NGT, Then MT-1186 Orally Period 1: a single dose of Edaravone oral suspension via NGT. Period 2 : a single dose of Edaravone oral suspension orally. | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | MT-1186 Orally, Then MT-1186 Via a Nasogastric Tube (NGT) | MT-1186 Via NGT, Then MT-1186 Orally | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 18 Participants | 36 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 18 Participants | 36 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 1 / 36 | 3 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
Apparent Distribution Volume at Elimination Phase (Vz/F) of Edaravone
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 Orally | Apparent Distribution Volume at Elimination Phase (Vz/F) of Edaravone | 1209 L | Standard Deviation 1682 |
| MT-1186 Via NGT | Apparent Distribution Volume at Elimination Phase (Vz/F) of Edaravone | 816 L | Standard Deviation 782 |
Primary
Apparent Distribution Volume at Steady State (Vss/F) of Edaravone
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 Orally | Apparent Distribution Volume at Steady State (Vss/F) of Edaravone | 183.7 L | Standard Deviation 299.9 |
| MT-1186 Via NGT | Apparent Distribution Volume at Steady State (Vss/F) of Edaravone | 125.4 L | Standard Deviation 67.7 |
Primary
Apparent Terminal Elimination Rate Constant (Kel) of Edaravone
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 Orally | Apparent Terminal Elimination Rate Constant (Kel) of Edaravone | 0.06430 1/h | Standard Deviation 0.03776 |
| MT-1186 Via NGT | Apparent Terminal Elimination Rate Constant (Kel) of Edaravone | 0.07713 1/h | Standard Deviation 0.03269 |
Primary
Apparent Total Clearance (CL/F) of Edaravone
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 Orally | Apparent Total Clearance (CL/F) of Edaravone | 42.8 L/h | Standard Deviation 12.3 |
| MT-1186 Via NGT | Apparent Total Clearance (CL/F) of Edaravone | 43.8 L/h | Standard Deviation 12.6 |
Primary
Area Under the Concentration Versus Time Curve (AUC) of Edaravone
Area under the plasma concentration versus time curve from time zero up to the last quantifiable concentration time-point (AUC0-t) of edaravone, and Area under the plasma concentration versus time curve from time zero up to infinity with extrapolation of the terminal phase (AUC0-inf) of edaravone.
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hours after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MT-1186 Orally | Area Under the Concentration Versus Time Curve (AUC) of Edaravone | AUC0-t | 2612 ng·h/mL | Standard Deviation 787 |
| MT-1186 Orally | Area Under the Concentration Versus Time Curve (AUC) of Edaravone | AUC0-inf | 2657 ng·h/mL | Standard Deviation 801 |
| MT-1186 Via NGT | Area Under the Concentration Versus Time Curve (AUC) of Edaravone | AUC0-t | 2592 ng·h/mL | Standard Deviation 866 |
| MT-1186 Via NGT | Area Under the Concentration Versus Time Curve (AUC) of Edaravone | AUC0-inf | 2617 ng·h/mL | Standard Deviation 870 |
Comparison: For AUC0-t, MT-1186 orally Versus MT-1186 via NGT90% CI: [0.936, 1.041]ANOVA
Comparison: For AUC0-inf, MT-1186 orally Versus MT-1186 via NGT90% CI: [0.931, 1.033]ANOVA
Primary
Maximum Plasma Concentration (Cmax) of Edaravone
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 Orally | Maximum Plasma Concentration (Cmax) of Edaravone | 2470 ng/mL | Standard Deviation 839.8 |
| MT-1186 Via NGT | Maximum Plasma Concentration (Cmax) of Edaravone | 2775 ng/mL | Standard Deviation 1444 |
Comparison: MT-1186 orally Versus MT-1186 via NGT90% CI: [0.903, 1.227]ANOVA
Primary
Mean Residence Time (MRT) of Edaravone
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 Orally | Mean Residence Time (MRT) of Edaravone | 4.66 h | Standard Deviation 8.89 |
| MT-1186 Via NGT | Mean Residence Time (MRT) of Edaravone | 2.89 h | Standard Deviation 1.44 |
Primary
Terminal Elimination Half-life (t1/2) of Edaravone
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 Orally | Terminal Elimination Half-life (t1/2) of Edaravone | 21.52 h | Standard Deviation 33.83 |
| MT-1186 Via NGT | Terminal Elimination Half-life (t1/2) of Edaravone | 13.53 h | Standard Deviation 13.81 |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Edaravone
Time frame: Plasma samples are collected: Day 1 and Day 4 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 and Day 5 at 24 and 36 hours; Day 3 and Day 6 at 48 hour after administration.
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MT-1186 Orally | Time to Reach Maximum Plasma Concentration (Tmax) of Edaravone | 0.50 h |
| MT-1186 Via NGT | Time to Reach Maximum Plasma Concentration (Tmax) of Edaravone | 0.25 h |
Secondary
Number of Participants With Adverse Events and Adverse Drug Reactions
Time frame: Day 1 to 11
Population: This study was designed as a 2-group, 2-period crossover study with the advance administration of edaravone orally group (Oral =\> NGT) with 18 subjects, and the advance administration of edaravone via NGT group (NGT =\> Oral) with 18 subjects to investigate the bioavailability between edaravone orally and via NGT.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MT-1186 Orally | Number of Participants With Adverse Events and Adverse Drug Reactions | Number of Participants with Adverse events | 1 Participants |
| MT-1186 Orally | Number of Participants With Adverse Events and Adverse Drug Reactions | Number of Participants with adverse drug reactions | 0 Participants |
| MT-1186 Via NGT | Number of Participants With Adverse Events and Adverse Drug Reactions | Number of Participants with Adverse events | 3 Participants |
| MT-1186 Via NGT | Number of Participants With Adverse Events and Adverse Drug Reactions | Number of Participants with adverse drug reactions | 1 Participants |