The study will evaluate the influence of hepatic insufficiency on the PK of ACP-196.
This is a 2-part study. Part 1 of the study will compare the PK of ACP-196 in participants with mild hepatic insufficiency (a score of 5 to 6, on the Child-Pugh scale) and moderate hepatic insufficiency (a score of 7 to 9, on the Child-Pugh scale) to healthy (mean) matched control participants for age and weight. Part 2 of the study, if it is conducted, will compare the PK of ACP-196 in participants with severe hepatic insufficiency (a score of 10 to 15 on the Child-Pugh scale) to the healthy control participants from Part 1. In Part 1, 6 participants with mild hepatic insufficiency, 6 participants with moderate hepatic, and 6 healthy control participants matched to the hepatic insufficiency groups according to mean age and mean weight will be enrolled. In Part 2, if conducted, 6 participants with severe hepatic insufficiency will be enrolled. The control group of Part 1 will be used for Part 2 PK comparison. Participants will be screened within 28 days before the dose. Participants will be contacted approximately 14 days after the last dose of study drug administration to determine if any adverse event has occurred since the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
All study participants will receive a single oral dose of 50 mg ACP-196 (2 x 25 mg capsules) on Day 1 of the study.
Research Site
Miami, Florida, United States
Research Site
Orlando, Florida, United States
Research Site
Knoxville, Tennessee, United States
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Maximum Observed Plasma Concentration (Cmax) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Area Under the Plasma Concentration-time Curve From Time 0 To Time of Last Measurable Concentration (AUC0-last) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Area Under the Plasma Concentration-time Curve From Time 0 To 24 Hours (AUC0-24) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Percent of AUC0inf Extrapolated (AUC%extrap) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Time of the Maximum Measured Plasma Concentration (Tmax) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
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Time of the Last Measurable Plasma Concentration (Tlast) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Apparent Terminal Elimination Rate Constant (λz) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Apparent Terminal Elimination Half-life (T1/2) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Apparent Total Body Clearance (CL/F) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Apparent Total Volume of Distribution (Vz/F) of ACP-196
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours (hrs) for all arms, additional timepoints at 36 and 48 hrs post dose for mild/moderate/severe hepatic insufficiency arms
Incidences of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From Day 1 through 14 days after the last dose (approximately 4 months)
Incidences of Abnormal Vital Signs and Physical Examinations Reported as TEAEs
Time frame: Day 1 through Day 3
Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Time frame: Day 1 through Day 3
Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs
Time frame: Day 1 through Day 3