Japanese Patients With ALS
Conditions
Brief summary
To evaluate the pharmacokinetics of single doses of edaravone oral suspension in Amyotrophic Lateral Sclerosis Patients with gastrostomy
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 80 Years
Healthy volunteers
No
Inclusion criteria
The key criteria are listed below. * Patients aged between 20 and 80 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 * ALS Patients with gastrostomy * 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 \<15.0 or \>30.0, or a body weight of \<40 kg * Patients 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 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, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration. | — |
| Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 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, 0.25, 0.5, 1, 2, 4 and 8 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, 0.25, 0.5, 1, 2, 4 and 8 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, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration. | — |
| Mean Residence Time (MRT) of Unchanged Edaravone | Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 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, 0.25, 0.5, 1, 2, 4 and 8 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, 0.25, 0.5, 1, 2, 4 and 8 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, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration | — |
| Cumulative Amount of Drug Excreted in Urine (Ae) of Edaravone | Urine samples are collected: 0 to 8 hours after oral administration | This information will not be disclosed because it may identify the patient (N=1). |
| Cumulative Percentage of Drug Excreted in Urine (Ae) of Edaravone | Urine samples are collected: 0 to 8 hours after oral administration | This information will not be disclosed because it may identify the patient (N=1) |
| Renal Clearance (CLr) of Edaravone | Urine samples are collected: 0 to 8 hours after oral administration | This information will not be disclosed because it may identify the patient (N=1). |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events and Adverse Drug Reactions | The provision of informed consent to Day 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 via a percutaneous endoscopic gastrostomy (PEG) tube. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | MT-1186 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 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 | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 3 / 6 |
| serious Total, serious adverse events | 2 / 6 |
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, 0.25, 0.5, 1, 2, 4 and 8 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 | 365 L | Standard Deviation 236 |
Primary
Apparent Distribution Volume at Steady State (Vss/F) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 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 | 101 L | Standard Deviation 48.1 |
Primary
Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Apparent Terminal Elimination Rate Constant (Kel) of Unchanged Edaravone | 0.1561 1/h | Standard Deviation 0.0138 |
Primary
Apparent Total Clearance (CL/F) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Apparent Total Clearance (CL/F) of Unchanged Edaravone | 54.4 L/h | Standard Deviation 28.1 |
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, 0.25, 0.5, 1, 2, 4 and 8 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 | 2300 ng·h/mL | Standard Deviation 950 |
Primary
Cumulative Amount of Drug Excreted in Urine (Ae) of Edaravone
This information will not be disclosed because it may identify the patient (N=1).
Time frame: Urine samples are collected: 0 to 8 hours after oral administration
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MT-1186 | Cumulative Amount of Drug Excreted in Urine (Ae) of Edaravone | NA mg |
Primary
Cumulative Percentage of Drug Excreted in Urine (Ae) of Edaravone
This information will not be disclosed because it may identify the patient (N=1)
Time frame: Urine samples are collected: 0 to 8 hours after oral administration
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MT-1186 | Cumulative Percentage of Drug Excreted in Urine (Ae) of Edaravone | NA percentage of dose |
Primary
Maximum Plasma Concentration (Cmax) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Maximum Plasma Concentration (Cmax) of Unchanged Edaravone | 2163 ng/mL | Standard Deviation 902.2 |
Primary
Mean Residence Time (MRT) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Mean Residence Time (MRT) of Unchanged Edaravone | 1.89 h | Standard Deviation 0.205 |
Primary
Renal Clearance (CLr) of Edaravone
This information will not be disclosed because it may identify the patient (N=1).
Time frame: Urine samples are collected: 0 to 8 hours after oral administration
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MT-1186 | Renal Clearance (CLr) of Edaravone | NA L/h |
Primary
Terminal Elimination Half-life (t1/2) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-1186 | Terminal Elimination Half-life (t1/2) of Unchanged Edaravone | 4.47 h | Standard Deviation 0.45 |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone
Time frame: Plasma samples are collected: Day 1 at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 hours; Day 2 at 24 hours after administration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MT-1186 | Time to Reach Maximum Plasma Concentration (Tmax) of Unchanged Edaravone | 0.29 h |
Secondary
Number of Participants With Adverse Events and Adverse Drug Reactions
Time frame: The provision of informed consent to Day 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 | 3 Participants |
| MT-1186 | Number of Participants With Adverse Events and Adverse Drug Reactions | Number of Participants with adverse drug reactions | 0 Participants |