A Study to Evaluate the Effect of an Acidic Formulation of Acalabrutinib (ACP-196), Acidic Beverage, or Grapefruit Juice on the Pharmacokinetics (PK) of ACP-196 Alone and Coadministered with Omeprazole

Study identifier:ACE-HV-112

ClinicalTrials.gov identifier:NCT04876807

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1, Single-center, Open-label, Fixed-sequence, 4-period, 3-part Study in Healthy Adult Subjects to Evaluate the Effect of an Acidic Formulation of Acalabrutinib (ACP-196), Acidic Beverage, or Grapefruit Juice on the Pharmacokinetics of Acalabrutinib Alone and Coadministered With Omeprazole

Medical condition

Healthy Volunteers

Phase

Phase 1

Healthy volunteers

Yes

Study drug

ACP-196, Omeprazole

Sex

All

Actual Enrollment

Study type

Interventional

Age

19 Years - 65 Years

Date

Study Start Date: 28 Jan 2016

Primary Completion Date: 15 Mar 2016

Study Completion Date: 15 Mar 2016

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jun 2021 by Acerta Pharma BV

Collaborators

Inclusion and exclusion criteria

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.

No locations available

Arms	Assigned Interventions
Experimental: Part 1 (Acidic formulation) In Part 1 of the study, the participants will receive Dose 1 of ACP-196 (reference or acidic formulation as applicable) with 240 mL water in 4 treatment schedules on Day 1, Day 3, Day 8 (with omeprazole), and Day 10 (with omeprazole).	Drug: ACP-196 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. Other Name: Acalabrutinib Drug: Omeprazole 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.
Experimental: Part 2 (Orange drink) In Part 2 of the study, the participants will receive Dose 1 of ACP-196 (reference formulation) with 240 mL water or acidic beverage as applicable in 4 treatment schedules on Day 1, Day 3, Day 8 (with omeprazole), and Day 10 (with omeprazole).	Drug: ACP-196 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. Other Name: Acalabrutinib Drug: Omeprazole 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.
Experimental: Part 3 (Grapefruit juice) In Part 3 of the study, the participants will receive Dose 1 of ACP-196 (reference formulation) with 240 mL water or grapefruit as applicable in 4 treatment schedules on Day 1, Day 3, Day 8 (with omeprazole), and Day 10 (with omeprazole).	Drug: ACP-196 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. Other Name: Acalabrutinib Drug: Omeprazole 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.

Documents available

CSR_synopsis_redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

Priti Patel

Investigators

Principal Investigator