Healthy, Hepatic 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 Hepatic impairment compared to subjects with normal hepatic 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 Hepatic impaired subjects (in addition) * A Child-Pugh score of 5 or 6 for subjects with mild hepatic impairment, and between 7 and 9, inclusive, for subjects with moderate hepatic impairment * Chronic and stable hepatic impairment Healthy subjects (in addition) * Subject with normal hepatic function * 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 drug abuse * Presence of alcohol abuse * Presence of active infection requiring antibiotics * Positive test for human immunodeficiency virus (HIV) antigen/antibody * Uncontrolled, or untreated hypertension defined as systolic blood pressure (SBP)\>160 mmHg and/or diastolic blood pressure (DBP)\>100 mmHg * eGFR \<60 mL/min/1.73m2 Hepatic impairment subject (in addition) * Subjects with severe ascites Healthy subject (in addition) * History or presence of any parenchymal hepatic disease * Positive test for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb)
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 Hepatic Impairment Child-Pugh score of 5 or 6 | 8 |
| Moderate Hepatic Impairment Child-Pugh score between 7 and 9 | 6 |
| Normal Hepatic Function normal hepatic function | 8 |
| Total | 22 |
Baseline characteristics
| Characteristic | Mild Hepatic Impairment | Moderate Hepatic Impairment | Normal Hepatic Function | Total |
|---|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 11.9 | 66.2 years STANDARD_DEVIATION 5.3 | 61.6 years STANDARD_DEVIATION 2.7 | 62.1 years STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 6 Participants | 8 Participants | 22 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 | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 1 / 6 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 8 |
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 Hepatic Impairment | AUC0-∞ | 727.55 ng*hr/mL | Standard Deviation 262.04 |
| Moderate Hepatic Impairment | AUC0-∞ | 751.52 ng*hr/mL | Standard Deviation 148.34 |
| Normal Hepatic Function | AUC0-∞ | 594.96 ng*hr/mL | Standard Deviation 63.58 |
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 Hepatic Impairment | AUC0-last | 716.86 ng*hr/mL | Standard Deviation 258.3 |
| Moderate Hepatic Impairment | AUC0-last | 739.28 ng*hr/mL | Standard Deviation 146.89 |
| Normal Hepatic Function | AUC0-last | 582.89 ng*hr/mL | Standard Deviation 58.33 |
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 Hepatic Impairment | Cmax | 538.1 ng/mL | Standard Deviation 182.3 |
| Moderate Hepatic Impairment | Cmax | 533.4 ng/mL | Standard Deviation 88.57 |
| Normal Hepatic Function | Cmax | 429 ng/mL | Standard Deviation 44.36 |
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 Hepatic Impairment | t½ | 3.14 hour | Standard Deviation 0.58 |
| Moderate Hepatic Impairment | t½ | 4.37 hour | Standard Deviation 1.9 |
| Normal Hepatic Function | t½ | 5.41 hour | Standard Deviation 6.58 |