Japanese Patients With ALS
Conditions
Brief summary
To evaluate the pharmacokinetics of single doses of edaravone oral suspension in Patients with Amyotrophic Lateral Sclerosis
Interventions
DRUGMT-1186
Suspension
Sponsors
Shionogi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
The key criteria are listed below. * Patients aged between 20 and 75 years at the time of informed consent * Japanese patients * Among patients with ALS, those "Clinically definite ALS," "Clinically probable ALS" or "Clinically probable-laboratory-supported ALS" according to El Escorial Revised Airlie House criteria * Patients who can consent to contraception * Patients who have thoroughly understood the contents of the study and voluntarily provided written informed consent to participate in the study
Exclusion criteria
The key criteria are listed below. * Patients in whom the possibility could not be ruled out that the current symptoms were symptoms of a disease requiring differential diagnosis, such as cervical spondylosis and multifocal motor neuropathy * Patients undergoing treatment for malignancy * Patients who have presence of clinically significant liver, heart, or renal disease requiring hospitalization (except ALS) and infections requiring antibiotics. Patients who have a problem in general condition and are judged ineligible by the Investigator * Body mass index (BMI) of \<18.0 or \>30.0, or a body weight of \<50 kg * Patients judged by the investigator (or subinvestigator) to be unsuitable for the study for any other reason
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Quantifiable Concentration Time-point (AUC0-t) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Mean Residence Time (MRT) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Apparent Total Clearance (CL/F) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Apparent Distribution Volume at Elimination Phase (Vz/F) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration. |
| Cumulative Amount of Drug Excreted in Urine From Time Zero up to 24 Hours (Ae0-24) of Unchanged Edaravone | Urine samples are collected: 0 to 24 hours after oral administration |
| Cumulative Percentage of Drug Excreted in Urine From Time Zero up to 24 Hours (Ae0-24) of Unchanged Edaravone | Urine samples are collected: 0 to 24 hours after oral administration |
| Renal Clearance (CLr) of Unchanged Edaravone | Urine samples are collected: 0 to 24 hours after oral administration |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events and Adverse Drug Reactions | Day 1 to 8 |
Countries
Japan
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MT-1186 ALS patients receive the edaravone oral suspension. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | MT-1186 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 1 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Apparent Distribution Volume at Elimination Phase (Vz/F) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Apparent Distribution Volume at Elimination Phase (Vz/F) of Unchanged Edaravone | 603 L | Standard Deviation 196 |
Primary
Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone | 155.7 L | Standard Deviation 85 |
Primary
Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone | 0.118 1/h | Standard Deviation 0.028 |
Primary
Apparent Total Clearance (CL/F) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Apparent Total Clearance (CL/F) of Unchanged Edaravone | 72.5 L/h | Standard Deviation 33.4 |
Primary
Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Quantifiable Concentration Time-point (AUC0-t) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Area Under the Plasma Concentration Versus Time Curve From Time Zero up to the Last Quantifiable Concentration Time-point (AUC0-t) of Unchanged Edaravone | 1719 ng·h/mL | Standard Deviation 808 |
Primary
Cumulative Amount of Drug Excreted in Urine From Time Zero up to 24 Hours (Ae0-24) of Unchanged Edaravone
Time frame: Urine samples are collected: 0 to 24 hours after oral administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Cumulative Amount of Drug Excreted in Urine From Time Zero up to 24 Hours (Ae0-24) of Unchanged Edaravone | 0.534 mg | Standard Deviation 0.11 |
Primary
Cumulative Percentage of Drug Excreted in Urine From Time Zero up to 24 Hours (Ae0-24) of Unchanged Edaravone
Time frame: Urine samples are collected: 0 to 24 hours after oral administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Cumulative Percentage of Drug Excreted in Urine From Time Zero up to 24 Hours (Ae0-24) of Unchanged Edaravone | 0.508 percentage | Standard Deviation 0.105 |
Primary
Maximum Plasma Concentration (Cmax) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | 1903 ng/mL | Standard Deviation 978.5 |
Primary
Mean Residence Time (MRT) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Mean Residence Time (MRT) of Unchanged Edaravone | 2.14 h | Standard Deviation 0.52 |
Primary
Renal Clearance (CLr) of Unchanged Edaravone
Time frame: Urine samples are collected: 0 to 24 hours after oral administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Renal Clearance (CLr) of Unchanged Edaravone | 0.374 L/h | Standard Deviation 0.232 |
Primary
Terminal Elimination Half-life (t1/2) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | 6.11 h | Standard Deviation 1.17 |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MT-1186 | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | 0.25 h |
Secondary
Number of Participants With Adverse Events and Adverse Drug Reactions
Time frame: Day 1 to 8
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MT-1186 | Number of Participants With Adverse Events and Adverse Drug Reactions | Number of Participants with Adverse events | 1 Participants |
| MT-1186 | Number of Participants With Adverse Events and Adverse Drug Reactions | Number of Participants with adverse drug reactions | 0 Participants |