This study will evaluate the effect of an acidic formulation of Acalabrutinib (ACP-196), acidic beverage, or grapefruit Juice on the PK of ACP-196 alone and coadministered with omeprazole.
This is a 3-part study. Each part of the study will compare the effect of an acidic formulation of ACP-196, acidic beverage (orange drink), or grapefruit juice on the PK profile of ACP-196 alone and when coadministered with omeprazole. Participants will be enrolled into Part 1 of the study first and then subsequent participants will be randomized in a 1:1 ratio to either Part 2 or Part 3 of the study. 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
36
In Parts 1, 2, and 3, participants will receive oral Dose 1 of ACP-196 (reference or acidic formulation as applicable) on Day 1, Day 3, Day 8, and Day 10.
Participants will receive omeprazole in all parts as: on Day 8 and Day 10 with water in Part 1; on Day 8 with water and on Day 10 with acidic beverage in Part 2; on Day 8 with water and on Day 10 with grapefruit juice in Part 3.
Laura Sterling, MD, MPH
Lincoln, Nebraska, United States
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Maximum Observed Plasma Concentration (Cmax) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Percent of AUC0inf Extrapolated (AUC%extrap) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6h) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Apparent Terminal Elimination Rate Constant (λz) of ACP-196 in Parts 1, 2, and 3
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Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Apparent Terminal Elimination Half-life (T1/2) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Apparent Total Plasma Clearance (CL/F) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Apparent Total Volume of Distribution (Vz/F) of ACP-196 in Parts 1, 2, and 3
Time frame: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) of Omeprazole in Parts 1, 2, and 3
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours on Days 8 and 10
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Omeprazole in Parts 1, 2, and 3
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours on Days 8 and 10
Maximum Observed Plasma Concentration (Cmax) of Omeprazole in Parts 1, 2, and 3
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours on Days 8 and 10
Time of the Maximum Measured Plasma Concentration (Tmax) of Omeprazole in Parts 1, 2, and 3
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours on Days 8 and 10
Apparent Total Plasma Clearance (CL/F) of Omeprazole in Parts 1, 2, and 3
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours on Days 8 and 10
Apparent Total Volume of Distribution (Vz/F) of Omeprazole in Parts 1, 2, and 3
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours on Days 8 and 10
Number of Participants With Treatment emergent Adverse Events (TEAEs) and Treatment emergent Serious Adverse Events (TESAEs) in Parts 1, 2, and 3
Time frame: From Day 1 through 14 days after the last dose (approximately 2 months)
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Parts 1, 2, and 3
Time frame: From Day 1 through 24 hours post last dose on Day 10 (approximately 2 months)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Parts 1, 2, and 3
Time frame: From Day 1 through 24 hours post last dose on Day 10 (approximately 2 months)