Trial Outcomes & Findings for Investigate the Influence of Severe Hepatic Impairment on the Pharmacokinetics of Acalabrutinib and Its Metabolite (NCT NCT03968848)
NCT ID: NCT03968848
Last Updated: 2021-09-10
Results Overview
Area Under the Concentration-Time Curve
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
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.
Results posted on
2021-09-10
Participant Flow
Participant milestones
| Measure |
Severe Hepatic Impairment
Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
Normal Hepatic Function
Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Investigate the Influence of Severe Hepatic Impairment on the Pharmacokinetics of Acalabrutinib and Its Metabolite
Baseline characteristics by cohort
| Measure |
Severe Hepatic Impairment
n=8 Participants
Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
Normal Hepatic Function
n=8 Participants
Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.6 Years
STANDARD_DEVIATION 7.96 • n=5 Participants
|
57.1 Years
STANDARD_DEVIATION 4.88 • n=7 Participants
|
57.4 Years
STANDARD_DEVIATION 6.39 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
USA
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
Severe Hepatic Impairment
n=8 Participants
Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
Normal Hepatic Function
n=8 Participants
Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
|---|---|---|
|
Plasma Acalabrutinib PK Parameters
AUC0-24
|
1167 ng*hr/mL
Geometric Coefficient of Variation 53.6
|
226.1 ng*hr/mL
Geometric Coefficient of Variation 55.3
|
|
Plasma Acalabrutinib PK Parameters
AUC0-last
|
1161 ng*hr/mL
Geometric Coefficient of Variation 53.9
|
220.0 ng*hr/mL
Geometric Coefficient of Variation 57.3
|
|
Plasma Acalabrutinib PK Parameters
AUC0-inf
|
1169 ng*hr/mL
Geometric Coefficient of Variation 53.8
|
226.5 ng*hr/mL
Geometric Coefficient of Variation 55.1
|
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
Severe Hepatic Impairment
n=8 Participants
Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
Normal Hepatic Function
n=8 Participants
Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
|---|---|---|
|
Maximum Plasma Acalabrutinib Concentration
|
726.0 ng/mL
Geometric Coefficient of Variation 56.2
|
147.7 ng/mL
Geometric Coefficient of Variation 116.8
|
Adverse Events
Severe Hepatic Impairment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Normal Hepatic Function
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Severe Hepatic Impairment
n=8 participants at risk
Subjects with severe hepatic impairment receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
Normal Hepatic Function
n=8 participants at risk
Subjects with normal hepatic function receiving a single dose of 50 mg acalabrutinib (1 x 50 mg capsules)
|
|---|---|---|
|
Metabolism and nutrition disorders
Hypokalaemia
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days post last dose
|
0.00%
0/8 • From first dose of study drug until 30 days post last dose
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days post last dose
|
0.00%
0/8 • From first dose of study drug until 30 days post last dose
|
Additional Information
Global Clinical Lead
AstraZeneca Clinical Study Information Center
Phone: 1-877-240-9479
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place