A study of Acalabrutinib suspension to evaluate relative bioavailability and proton-pump inhibitor effect in healthy volunteers

Study identifier:D822FC00004

ClinicalTrials.gov identifier:NCT04435483

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Phase I, Open-label, Single-dose, Sequential, Randomized, Crossover Study of Acalabrutinib Suspension Delivered via Nasogastric Tube in Healthy Subjects to Evaluate Relative Bioavailability and Proton-pump Inhibitor (Rabeprazole) Effect

Medical condition

pharmacokinetics, Bioavailability

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Acalabrutinib Treatment A, Acalabrutinib Treatment B, Acalabrutinib Treatment C

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 22 May 2020

Primary Completion Date: 26 Jun 2020

Study Completion Date: 26 Jun 2020

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2021 by AstraZeneca

Collaborators

Acerta Pharma

Inclusion and exclusion 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.

No locations available

Arms	Assigned Interventions
Experimental: 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.	Drug: 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. Drug: Acalabrutinib Treatment B Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions. 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.
Experimental: 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.	Drug: Acalabrutinib Treatment B Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions. 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.

Arms

Assigned Interventions

Experimental: 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.

Drug: 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.

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

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.

Experimental: 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.

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

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.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

David Han

Parexel Early Phase Clinical Unit (Los Angeles)