Healthy Subjects, Hepatic Impairment, Hepatic Insufficiency
Conditions
Keywords
Hepatic, Acalabrutinib
Brief summary
This study is investigate the influence of severe hepatic impairment on the pharmacokinetics of acalabrutinib and its metabolite.
Interventions
DRUGacalabrutinib
A 50-mg single oral dose of acalabrutinib will be administered.
Sponsors
AstraZeneca
Acerta Pharma BV
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Women must be of non childbearing status * Understands the study procedures in the ICF and be willing and able to comply with the protocol. * Willingness and ability to swallow study drug capsule. * Adult men or women, 18 to 75 years of age Hepatic-Impaired Subjects Only: * Subject has a diagnosis of chronic, stable HI. * Subject's score on the Child-Pugh scale must range from 10 to 15 at screening.
Exclusion criteria
* History or presence of clinically significant or unstable medical or psychiatric condition or disease in the opinion of the PI. * Dosed in another clinical trial within 28 days before dosing of study drug and throughout the current study. * History or presence of drug abuse within 2 years before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Acalabrutinib PK Parameters | Severe HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72 hrs post-dose. Normal HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs post-dose. | Area Under the Concentration-Time Curve |
| Maximum Plasma Acalabrutinib Concentration | Severe HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72 hrs post-dose. Normal HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs post-dose. | Maximum Cmax |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Severe Hepatic Impairment Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | 8 |
| Normal Hepatic Function Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules) | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Severe Hepatic Impairment | Normal Hepatic Function | Total |
|---|---|---|---|
| Age, Continuous | 57.6 Years STANDARD_DEVIATION 7.96 | 57.1 Years STANDARD_DEVIATION 4.88 | 57.4 Years STANDARD_DEVIATION 6.39 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment USA | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 1 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Maximum Plasma Acalabrutinib Concentration
Maximum Cmax
Time frame: Severe HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72 hrs post-dose. Normal HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs post-dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Severe Hepatic Impairment | Maximum Plasma Acalabrutinib Concentration | 726.0 ng/mL | Geometric Coefficient of Variation 56.2 |
| Normal Hepatic Function | Maximum Plasma Acalabrutinib Concentration | 147.7 ng/mL | Geometric Coefficient of Variation 116.8 |
Primary
Plasma Acalabrutinib PK Parameters
Area Under the Concentration-Time Curve
Time frame: Severe HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24, 36, 48, 60, 72 hrs post-dose. Normal HI: pre-dose, and 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs post-dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Severe Hepatic Impairment | Plasma Acalabrutinib PK Parameters | AUC0-24 | 1167 ng*hr/mL | Geometric Coefficient of Variation 53.6 |
| Severe Hepatic Impairment | Plasma Acalabrutinib PK Parameters | AUC0-last | 1161 ng*hr/mL | Geometric Coefficient of Variation 53.9 |
| Severe Hepatic Impairment | Plasma Acalabrutinib PK Parameters | AUC0-inf | 1169 ng*hr/mL | Geometric Coefficient of Variation 53.8 |
| Normal Hepatic Function | Plasma Acalabrutinib PK Parameters | AUC0-24 | 226.1 ng*hr/mL | Geometric Coefficient of Variation 55.3 |
| Normal Hepatic Function | Plasma Acalabrutinib PK Parameters | AUC0-last | 220.0 ng*hr/mL | Geometric Coefficient of Variation 57.3 |
| Normal Hepatic Function | Plasma Acalabrutinib PK Parameters | AUC0-inf | 226.5 ng*hr/mL | Geometric Coefficient of Variation 55.1 |