A Study to Evaluate Effects of Proton-pump Inhibitor on Acalabrutinib Capsule When Administered Orally With COCA-COLA in Healthy Participants

NCT04489797 | Completed Phase 1 FDA Drug

• 1 other identifier: D822FC00008
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to support the clinical development of acalabrutinib in participants who need treatment with proton pump inhibitors while taking acalabrutinib.

Conditions

Infectious Disease

Keywords

Pharmacokinetics; Bioavailability

Outcome Measures

Primary Outcomes (3)

• Area under plasma concentration-time curve from time zero to infinity (AUCinf)

  Assessment of AUCinf for acalabrutinib and ACP-5862 (metabolite of acalabrutinib) following administration of capsule with and without rabeprazole.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2

• Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)

  Assessment of AUClast for acalabrutinib and ACP-5862 following administration of capsule with and without rabeprazole.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2

• Maximum observed plasma concentration (Cmax)

  Assessment of Cmax for acalabrutinib and ACP-5862 following administration of capsule with and without rabeprazole.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2

Secondary Outcomes (1)

• Number of participants with adverse events and serious adverse events

  From screening until Follow-up visit (Upto 5 to 6 Weeks)

Study Arms (2)

Arm A

EXPERIMENTAL

Participants will receive single oral dose of acalabrutinib capsule with 100 mL of water.

Drug: Acalabrutinib

Arm B

EXPERIMENTAL

Participants will receive single oral dose of acalabrutinib capsule taken with 100 mL of COCA-COLA along with 20 mg rabeprazole.

Drug: Acalabrutinib; Drug: Rabeprazole

Interventions

Acalabrutinib DRUG

Participants will receive single oral dose of acalabrutinib on day 1 as per the arms they are randomized.

Arm A; Arm B

Rabeprazole DRUG

Participants will receive twice daily oral dose of 20 mg rabeprazole on days -3, -2, and -1.

Arm B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Capable of giving signed informed consent.
• Male participants and their female partners/spouses must adhere to the contraception methods.
• Female participants must have a negative pregnancy test at screening, must not be lactating, and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
• Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and follicle stimulating hormone levels in the postmenopausal range.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not bilateral tubal ligation.
• Have a body mass index between 18.5 and 30 kg/m\^2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive, at screening.
• Understands the study procedures in the informed consent form and willing and able to comply with the protocol.

You may not qualify if:

• History or presence of any clinically significant disease (including active coronavirus disease 2019 infection).
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 30 days of the first administration of investigational medicinal product (IMP).
• Any clinically significant abnormalities in hematology, coagulation, clinical chemistry, or urinalysis results, at screening defined as:
• Hemoglobin less than lower limit of normal.
• Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase or serum bilirubin (total and direct) \> 1.5 upper limit of normal.
• Any clinically significant abnormal findings in vital signs at screening (eg, systolic blood pressure \[BP\] \< 90 mmHg or ≥ 140 mmHg; diastolic BP \< 50 mmHg or ≥ 90 mmHg; pulse \< 50 or \> 90 bpm).
• Any clinically significant abnormalities on standard 12-lead electrocardiogram at screening.
• Any positive result on screening for serum Hepatitis B surface antigen, hepatitis B, hepatitis C, and Human immunodeficiency virus antibody.
• Plasma donation within 30 days of screening or any blood donation/loss more than 500 mL during the 90 days prior to screening.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to acalabrutinib or rabeprazole.
• Current smokers or those who have smoked or used nicotine products within the 90 days prior to screening.
• Positive screen for drugs of abuse or cotinine at screening.
• Treatment with a strong cytochrome P450 3A (CYP3A) inhibitor (within 14 days before first administration of IMP) or strong CYP3A inducer (within 28 days before first administration of IMP).
• Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 14 days prior to the first administration of IMP or longer if the medication has a long half-life. Hormonal replacement therapy will not be allowed.

Sponsors & Collaborators

• AstraZeneca: lead
• Acerta Pharma BV: collaborator

Study Sites (1)

Research Site

Anaheim, California, 92801, United States

Location

MeSH Terms

Conditions

Communicable Diseases

Interventions

acalabrutinib; Rabeprazole

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Peter J. Winkle, MD FACP FACG CPI

  Anaheim Clinical Trials

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is open-label, randomized, single-dose study. The participants will be divided in 2 treatment arms as follows: 1. Arm A (only acalabrutinib) 2. Arm B (acalabrutinib + rabeprazole)

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 28, 2020
• Study Start: July 20, 2020
• Primary Completion: August 28, 2020
• Study Completion: August 28, 2020
• Last Updated: October 30, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (1)