A Study of Acalabrutinib Suspension to Evaluate Relative Bioavailability and Proton-pump Inhibitor Effect in Healthy Volunteers

NCT ID: NCT04435483

Last Updated: 2020-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-22
• Study Completion Date: 2020-06-26

Brief Summary

This study is being conducted to support the clinical development of acalabrutinib in patients who are unable to swallow capsule and require nasogastric (NG) tube placement.

Detailed Description

This is an open-label, single-center, randomized, 3-period, crossover study of acalabrutinib suspension administered via NG tube in healthy subjects to evaluate the relative bioavailability and proton-pump inhibitor (rabeprazole) effect.

The study is divided in 3 periods.

Period 1 of the study is designed to investigate the effect of proton-pump inhibitor on the pharmacokinetics (PK) of acalabrutinib suspension. Period 2 and 3 of the study are designed to investigate the bioavailability of acalabrutinib suspension relative to an oral capsule formulation.

Conditions

Pharmacokinetics; Bioavailability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Sequence 1

Participants will receive Treatment A (100 mg acalabrutinib suspension via NG administration plus 20 mg rabeprazole) in Period 1, Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 2, and Treatment C (100 mg acalabrutinib capsule) in Period 3.

Group Type: EXPERIMENTAL

Acalabrutinib Treatment A

Intervention Type: DRUG

Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions. A single dose of 20 mg rabeprazole will be administered with 240 mL water, 2 hours prior to administration of acalabrutinib suspension. Treatment with rabeprazole 20 mg twice daily (with meals) will be started 3 days prior to the receiving the first dose of acalabrutinib suspension.

Acalabrutinib Treatment B

Intervention Type: DRUG

Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions.

Acalabrutinib Treatment C

Intervention Type: DRUG

Participants will receive a single dose of 100-mg acalabrutinib capsule, under fasted conditions. The acalabrutinib capsule will be administered with 240 mL of water.

Treatment Sequence 2

Participants will receive Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 1, Treatment C (100 mg acalabrutinib capsule) in Period 2, and Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 3.

Group Type: EXPERIMENTAL

Acalabrutinib Treatment B

Intervention Type: DRUG

Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions.

Acalabrutinib Treatment C

Intervention Type: DRUG

Participants will receive a single dose of 100-mg acalabrutinib capsule, under fasted conditions. The acalabrutinib capsule will be administered with 240 mL of water.

Interventions

Acalabrutinib Treatment A

Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions. A single dose of 20 mg rabeprazole will be administered with 240 mL water, 2 hours prior to administration of acalabrutinib suspension. Treatment with rabeprazole 20 mg twice daily (with meals) will be started 3 days prior to the receiving the first dose of acalabrutinib suspension.

Intervention Type: DRUG

Acalabrutinib Treatment B

Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions.

Intervention Type: DRUG

Acalabrutinib Treatment C

Participants will receive a single dose of 100-mg acalabrutinib capsule, under fasted conditions. The acalabrutinib capsule will be administered with 240 mL of water.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated, written informed consent prior to any study-specific procedures.

2. Healthy adult male and female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.

3. Male subjects and their female partners/spouses must adhere to the contraception methods.

4. Female subjects must have a negative pregnancy test at screening, must not be lactating, and must be of non-childbearing potential.

5. Have a body mass index (BMI) between 18.5 and 30 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive, at screening.

Exclusion Criteria

1. History or presence of any clinically significant disease (including COVID-19) or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.

2. History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.

3. Any positive result on screening for serum hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

4. Plasma donation within 30 days of screening or any blood donation/loss more than 500 mL during the 90 days prior to screening.

5. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 90 days prior to screening.

6. Positive screen for drugs of abuse or cotinine at screening.

7. Known or suspected history of alcohol or drug abuse, or excessive intake of alcohol as judged by the Investigator.

8. Excessive intake of caffeine-containing drinks or food as judged by the Investigator.

9. Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

10. History of a disorder which would make NG tube placement contraindicated, eg, esophageal strictures, esophageal varices, or bleeding diathesis.

11. Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections). Subjects with localized cutaneous fungal infections are eligible.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Acerta Pharma, LLC

OTHER

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Han, M.D.

Role: PRINCIPAL_INVESTIGATOR

PAREXEL Early Phase Clinical Unit-Los Angeles

Locations

Research Site

Glendale, California, United States

Countries

United States

Other Identifiers

D822FC00004

Identifier Type: -

Identifier Source: org_study_id