A Study to Evaluate Relative Bioavailability, Proton Pump Inhibitor (PPI) (Rabeprazole) Effect, Food Effect and Particle Size Effect of New Acalabrutinib Tablet in Healthy Subjects

NCT04488016 | Completed Phase 1 FDA Drug

• 1 other identifier: D8220C00018
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be a 2-part, open-label, single-center relative bioavailability, PPI effect, food-effect and particle size effect randomized crossover study of acalabrutinib tablets in healthy subjects (males or females). The study will be divided in 2 study parts; following a review of the safety and Pharmacokinetics (PK) data from Part 1, the study is planned to be continued with Part 2.

Conditions

Bioavailability; B-cell Lymphoid Cancer

Keywords

Bruton tyrosine kinase (BTK) inhibitor; Proton Pump Inhibitor (Rabeprazole) Effect; Food Effect; Particle Size Effect

Outcome Measures

Primary Outcomes (3)

• Maximum observed plasma concentration (Cmax)-Acalabrutinib

  Part 1: To assess the relative bioavailability of the acalabrutinib tablet compared with acalabrutinib capsules in fasted state. Part 2: To assess the impact of drug substance particle size on the bioavailability of acalabrutinib tablets.

  Day 1 and Day 2

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

  Part 1: To assess the relative bioavailability of the acalabrutinib tablet compared with acalabrutinib capsules in fasted state. Part 2: To assess the impact of drug substance particle size on the bioavailability of acalabrutinib tablets.

  Day 1 and Day 2

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

  Part 1: To assess the relative bioavailability of the acalabrutinib tablet compared with acalabrutinib capsules in fasted state. Part 2: To assess the impact of drug substance particle size on the bioavailability of acalabrutinib tablets.

  Day 1 and Day 2

Secondary Outcomes (52)

• Cmax -ACP-5862

  Day 1 and Day 2

• AUClast-ACP-5862

  Day 1 and Day 2

• AUCinf-ACP-5862

  Day 1 and Day 2

• Area under the plasma concentration-time curve from time zero to 12 hours post-dose (AUC0-12) - Acalabrutinib and ACP-5862

  Day 1 and Day 2

• AUClast- Acalabrutinib and ACP-5862

  Day 1 and Day 2

Study Arms (6)

Cohort 1 -Part 1

EXPERIMENTAL

Subjects will be randomized to one of 4 sequences ABC, BAC, ABD, or BAD. Subjects will receive 100 mg acalabrutinib capsule, fasted state (\>10 h) in Treatment A , 100 mg acalabrutinib tablet (Variant 1), fasted state (\>10 h) in Treatment B, 100 mg acalabrutinib tablet (Variant 1), fed state in Treatment C, Rabeprazole 20 mg ×1 (fasted) at 2 hours before administration of 100 mg acalabrutinib tablet (Variant 1)\* and following prior administration of rabeprazole 20 mg BID (with meals) on Days -3, -2 and -1 in Treatment D.

Drug: Treatment A- Part 1; Drug: Treatment B- Part 1; Drug: Treatment C - Part 1

Cohort 2- Part 1

EXPERIMENTAL

Subjects will be randomized to one of 4 sequences ABC, BAC, ABD, or BAD. Subjects will receive 100 mg acalabrutinib capsule, fasted state (\>10 h) in Treatment A , 100 mg acalabrutinib tablet (Variant 1), fasted state (\>10 h) in Treatment B, 100 mg acalabrutinib tablet (Variant 1), fed state in Treatment C, Rabeprazole 20 mg ×1 (fasted) at 2 hours before administration of 100 mg acalabrutinib tablet (Variant 1)\* and following prior administration of rabeprazole 20 mg BID (with meals) on Days -3, -2 and -1 in Treatment D.

Drug: Treatment A- Part 1; Drug: Treatment B- Part 1; Drug: Treatment C - Part 1

Cohort 3- Part 1

EXPERIMENTAL

Subjects will be randomized to one of 4 sequences ABC, BAC, ABD, or BAD. Subjects will receive 100 mg acalabrutinib capsule, fasted state (\>10 h) in Treatment A , 100 mg acalabrutinib tablet (Variant 1), fasted state (\>10 h) in Treatment B, 100 mg acalabrutinib tablet (Variant 1), fed state in Treatment C, Rabeprazole 20 mg ×1 (fasted) at 2 hours before administration of 100 mg acalabrutinib tablet (Variant 1)\* and following prior administration of rabeprazole 20 mg BID (with meals) on Days -3, -2 and -1 in Treatment D.

Drug: Treatment A- Part 1; Drug: Treatment B- Part 1; Drug: Treatment C - Part 1; Drug: Treatment D- Part 1

Cohort 4 - Part 1

EXPERIMENTAL

Subjects will be randomized to one of 4 sequences: ABC, BAC, ABD, or BAD. Subjects will receive 100 mg acalabrutinib capsule, fasted state (\>10 h) in Treatment A , 100 mg acalabrutinib tablet (Variant 1), fasted state (\>10 h) in Treatment B, 100 mg acalabrutinib tablet (Variant 1), fed state in Treatment C, Rabeprazole 20 mg ×1 (fasted) at 2 hours before administration of 100 mg acalabrutinib tablet (Variant 1)\* and following prior administration of rabeprazole 20 mg BID (with meals) on Days -3, -2 and -1 in Treatment D.

Drug: Treatment A- Part 1; Drug: Treatment B- Part 1; Drug: Treatment C - Part 1; Drug: Treatment D- Part 1

Cohort 1- Part 2

EXPERIMENTAL

Subjects will be randomized to one of 2 sequences in a 2×4 crossover: ABCD or BADC. In Part 2, subjects will be receiving 100 mg acalabrutinib tablet (Variant 1), Variant 2, Variant 3, and 100 mg acalabrutinib solution.

Drug: Treatment A-Part 2; Drug: Treatment B - Part 2; Drug: Treatment C - Part 2; Drug: Treatment D - Part 2

Cohort 2 - Part 2

EXPERIMENTAL

Subjects will be randomized to one of 2 sequences in a 2×4 crossover: ABCD or BADC.In Part 2, subjects will be receiving 100 mg acalabrutinib tablet (Variant 1), Variant 2, Variant 3, and 100 mg acalabrutinib solution.

Drug: Treatment A-Part 2; Drug: Treatment B - Part 2; Drug: Treatment C - Part 2; Drug: Treatment D - Part 2

Interventions

Treatment A- Part 1 DRUG

Subjects will receive 100 mg acalabrutinib capsule, fasted state;

Cohort 1 -Part 1; Cohort 2- Part 1; Cohort 3- Part 1; Cohort 4 - Part 1

Treatment B- Part 1 DRUG

Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fasted state

Cohort 1 -Part 1; Cohort 2- Part 1; Cohort 3- Part 1; Cohort 4 - Part 1

Treatment C - Part 1 DRUG

Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fed state

Cohort 1 -Part 1; Cohort 2- Part 1; Cohort 3- Part 1; Cohort 4 - Part 1

Treatment D- Part 1 DRUG

Subjects will receive Rabeprazole 20 mg QD (fasted) at 2 hours before administration of 100 mg acalabrutinib tablet (Variant 1) and following prior administration of rabeprazole 20 mg Twice per day (BID) (with meals) on Days -3, -2 and -1.

Cohort 3- Part 1; Cohort 4 - Part 1

Treatment A-Part 2 DRUG

Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fasted state

Cohort 1- Part 2; Cohort 2 - Part 2

Treatment B - Part 2 DRUG

Subjects will receive 100 mg acalabrutinib tablet (Variant 2), fasted state

Cohort 1- Part 2; Cohort 2 - Part 2

Treatment C - Part 2 DRUG

Subjects will receive 100 mg acalabrutinib tablet (Variant 3), fasted state

Cohort 1- Part 2; Cohort 2 - Part 2

Treatment D - Part 2 DRUG

Subjects will receive 100 mg acalabrutinib solution, (Variant 4), fasted state

Cohort 1- Part 2; Cohort 2 - Part 2

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy adult male or female subjects aged 18 - 55 years with suitable veins for cannulation or repeated venipuncture.
• Male subject must adhere to the contraception methods.
• Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening.
• 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.
• Understands the study procedures in the Informed Consent Form (ICF) and willing and able to comply with the protocol.
• Willingness and ability to swallow study drugs, including the SmartPill.
• Willingness to consume a standardized, high- calorie, high-fat FDA breakfast.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Principal Investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• 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.
• Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections).
• Any clinically significant illness, medical/surgical procedure, or trauma within 30 days of the first administration of IMP.
• Any clinically significant abnormalities in clinical chemistry, hematology, coagulation, or urinalysis results, at screening and first admission to the study unit (first treatment period) as judged by the PI, and defined as: (1) Serum Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and serum bilirubin (total and direct)
• \> Upper limit of normal (ULN). (2) Hemoglobin \< ULN.
• Any clinically significant abnormal findings in vital signs at screening and first admission to the study unit (first treatment period), as judged by the PI.
• Any clinically significant abnormalities on 12-lead ECG at screening and first admission to the study unit (first treatment period), as judged by the PI.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis B core antibody (anti-HBc), hepatitis C antibody, and HIV antibody.
• Known or suspected history of drug abuse, as judged by the PI.
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 90 days of the first administration of IMP in this study.
• 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, as judged by the PI 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 (including e-cigarettes) within the 90 days prior to screening.
• Positive screen for drugs of abuse or cotinine at screening or on each admission to the study center or positive screen for alcohol on each admission to the study center.

Sponsors & Collaborators

• AstraZeneca: lead
• Acerta Pharma, LLC: collaborator

Study Sites (1)

Research Site

Baltimore, Maryland, 21225, United States

Location

Study Officials

• Ronald Goldwater,, MD

  PAREXEL Early Phase Clinical Unit Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: July 27, 2020
• Study Start: June 24, 2020
• Primary Completion: January 20, 2021
• Study Completion: January 20, 2021
• Last Updated: February 3, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)