Inclusion Criteria:  Continuous non-smoker who has not used nicotine-containing products for ≥ 3 months before the first dose. Body mass index (BMI) >= 18.0 and =< 32.0 kg/m^2 at screening. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms, as deemed by the principal investigator (PI). Liver function tests must be =< the upper limit of normal range (ULN) at screening for inclusion. Men and women of reproductive potential to follow protocol defined contraception methods. Women must have negative serum pregnancy test results. Willing and able to take the study drug with 240 mL of orange drink (Part 2) or grapefruit juice (Part 3).  Exclusion Criteria:  Participant is mentally or legally incapacitated, or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. Participant with known fruit allergies. History or presence of clinically significant medical or psychiatric condition or disease (eg, cardiovascular, respiratory, hepatic, gastrointestinal, renal, genitourinary, endocrine, neuromuscular, rheumatologic, oncologic, cutaneous or other disorders), in the opinion of the PI. History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study. Presence of any clinically significant, ongoing systemic bacterial, fungal or viral infections in the opinion of the PI. History or presence of alcoholism or drug abuse within the past 2 years before screening. History of bleeding diathesis (eg, hemophilia, von Willebrand disease). Any clinically significant condition that may affect acalabrutinib absorption in the opinion of the PI, including gastric restrictions and bariatric surgery (eg, gastric bypass). History or presence of clinically significant thyroid disease, in the opinion of the PI. Women who are pregnant or breastfeeding. Positive urine drug or alcohol results at screening or check-in. Positive urine cotinine at screening. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV). Seated blood pressure is < 90/40 mm Hg or > 140/90 mm Hg at screening. Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening. Have been on a diet incompatible with the on study diet, in the opinion of the PI, within the 28 days before the first dose of study drug, and throughout the study. Unable to refrain from or anticipates the use of protocol defined medicines: Donation of blood or significant blood loss within 56 days before the first dose of study drug. Plasma donation within 7 days before the first dose of study drug. Prior exposure to acalabrutinib (ACP-196). History or presence of clinically significant hypersensitivity or idiosyncratic reaction to acalabrutinib, omeprazole, related compounds (eg, substituted benzimidazoles, other azole compounds), or any inactive ingredients. History or presence of liver disease and Clostridium difficile-associated diarrhea.