Healthy, Renal Impairment
Conditions
Brief summary
To assess the pharmacokinetics of MCI-186 after a single intravenous infusion of 30mg/hour in subjects with mild or moderate renal impairment compared to subjects with normal renal function.
Interventions
DRUGMCI-186
30 mg of edaravone will be administered intravenously over 60 minutes.
Sponsors
Shionogi
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
All subjects * Able to provide written informed consent to participate in this study after reading the ICF * Subjects is able to understand and willing to cooperate and comply with the Protocol restrictions and requirements * A body weight of ≥45 kg in males or ≥40 kg in females and a body mass index ranging from 18 to 30 kg/m2 Renal impaired subjects (in addition) * Subjects with mild renal impairment defined as eGFR 60-89 mL/min/1.73m2 and subjects with moderate renal impairment defined as eGFR 30-59 mL/min/1.73m2 * Chronic and stable renal impairment Healthy subjects (in addition) * Subject with normal renal function defined as eGFR≥90 mL/min/1.73m2 * Good health and free from clinically significant illness or disease
Exclusion criteria
All subjects * Presence or history of severe allergy to food, or any medicinal product or relevant excipient that is of clinical significance * Subjects were previously administered MCI-186 * Positive urine drug screen (if not due to concomitant medication) or alcohol test * History of alcohol abuse or drug abuse * Presence of active infection requiring antibiotics * Positive test for human immunodeficiency virus (HIV) antigen/antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb) Renal impairment subject (in addition) * Acute renal failure * History of renal transplantation * Aspartate aminotransferase (AST) activity, or an alanine aminotransferase (ALT) activity of at least 3 times the upper limit of normal (ULN) range * Uncontrolled, or untreated hypertension defined as systolic blood pressure (SBP)\>180 mmHg and/or diastolic blood pressure (DBP)\>110 mmHg * Start of any new medication or new any changes to a current dosage Healthy subject (in addition) * History or presence of any renal disease * Uncontrolled, or untreated hypertension defined as systolic blood pressure (SBP)\>160 mmHg and/or diastolic blood pressure (DBP)\>100 mmHg
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax | pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose |
| AUC0-last | pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose |
| AUC0-∞ | pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose |
Secondary
| Measure | Time frame |
|---|---|
| t½ | pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose |
Countries
Japan
Contacts
STUDY_DIRECTORShionogi Clinical Trials Administrator Clinical Support Help Line
Shionogi
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mild Renal Function Group Mild renal function defined as eGFR 60-89 mL/min/1.73m\^2 | 11 |
| Moderate Renal Function Group Moderate renal function defined as eGFR 30-59 mL/min/1.73m\^2 | 8 |
| Normal Renal Function Group Normal renal function defined as eGFR ≥90 mL/min/1.73m\^2 | 11 |
| Total | 30 |
Baseline characteristics
| Characteristic | Mild Renal Function Group | Moderate Renal Function Group | Normal Renal Function Group | Total |
|---|---|---|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 5.1 | 57.9 years STANDARD_DEVIATION 8.4 | 47.3 years STANDARD_DEVIATION 4.3 | 45.8 years STANDARD_DEVIATION 10.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 8 Participants | 11 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 9 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 8 | 0 / 11 |
| other Total, other adverse events | 5 / 11 | 0 / 8 | 1 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 8 | 0 / 11 |
Outcome results
Primary
AUC0-∞
Time frame: pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Renal Function Group | AUC0-∞ | 770.97 ng*hr/mL | Standard Deviation 153.63 |
| Moderate Renal Function Group | AUC0-∞ | 826.44 ng*hr/mL | Standard Deviation 149.44 |
| Normal Renal Function Group | AUC0-∞ | 644.85 ng*hr/mL | Standard Deviation 153.14 |
Primary
AUC0-last
Time frame: pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Renal Function Group | AUC0-last | 758 ng*hr/mL | Standard Deviation 148.09 |
| Moderate Renal Function Group | AUC0-last | 808.7 ng*hr/mL | Standard Deviation 152.01 |
| Normal Renal Function Group | AUC0-last | 638.09 ng*hr/mL | Standard Deviation 151.98 |
Primary
Cmax
Time frame: pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Renal Function Group | Cmax | 545.4 ng/mL | Standard Deviation 92.59 |
| Moderate Renal Function Group | Cmax | 593.2 ng/mL | Standard Deviation 115.4 |
| Normal Renal Function Group | Cmax | 475.9 ng/mL | Standard Deviation 95.32 |
Secondary
t½
Time frame: pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h and 48h post-dose
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Renal Function Group | t½ | 5.38 hour | Standard Deviation 6.04 |
| Moderate Renal Function Group | t½ | 7.31 hour | Standard Deviation 5.83 |
| Normal Renal Function Group | t½ | 2.87 hour | Standard Deviation 0.38 |