NCT04488016

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

A 2-Part, Phase I, Open-label, Single-Dose, Sequential Randomized Crossover Study of New Acalabrutinib Tablet in Healthy Subjects to Evaluate Relative Bioavailability, Proton Pump Inhibitor (Rabeprazole) Effect, Food Effect and Particle Size Effect

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

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.

Detailed description

The study will be divided in 2 study parts; Part 1 of this study will be an open-label, 3-treatment-period, 4-treatment, single-center relative bioavailability, PPI effect, and food-effect randomized crossover study of a new acalabrutinib tablet in healthy subjects (males or females). The relative bioavailability part of Study Part 1 is designed to investigate the PK of the acalabrutinib tablet compared with the PK of acalabrutinib capsule, when administered as a single dose with water under the fasted condition (\>10 hours). The PPI effect part of Study Part 1 is designed to compare the PK of acalabrutinib tablet with or without coadministration of the PPI rabeprazole. The food-effect part of Study Part 1 is designed to compare the PK of acalabrutinib tablet under fed and fasted conditions. For each subject, a SmartPill will be administered with 120 mL of still water followed immediately by a single oral dose of acalabrutinib tablet (Treatment B, C or D) or acalabrutinib capsule (Treatment A) administered with 120 mL of still water. Study Part 1 will comprise: * A screening period of maximum 28 days; * Three treatment periods during which subjects will be resident from prior to the evening meal the night before dosing with Investigational medicinal product (IMP) (Day -1) until at least 48 hours after dosing; discharged on the morning of Day 3; and * A Follow-up Visit within 7 to 10 days. There will be a minimum washout period of at least 7 days between each acalabrutinib administration. A decision to continue with Study Part 2 will be made following a review of the preliminary data for relative bioavailability (acalabrutinib tablet versus acalabrutinib capsule), food effect, PPI effect, and safety observed in Part 1. Part 2 of this study will be an open-label, 4-treatment-period, 4-treatment, single-center relative bioavailability, randomized crossover study to determine the effect of particle size on the PK of a single dose of acalabrutinib tablet in healthy subjects (males or females). This relative bioavailability study is designed to investigate the PK of acalabrutinib tablets with various drug substance particle size distributions and the PK of acalabrutinib solution at a single oral dose of 100 mg under the fasted condition (\>10 hours). Study Part 2 will comprise: * A screening period of maximum 28 days; * Four treatment periods during which subjects will be resident prior to the evening meal the night before dosing with IMP (Day -1) until at least 48 hours after dosing; discharged on the morning of Day 3; and * A Follow-up Visit within 7 to 10 days. There will be a minimum washout period of at least 3 days between each acalabrutinib administration.

Conditions

• Bioavailability
• B-cell Lymphoid Cancer

Interventions

Type	Name	Description
DRUG	Treatment A- Part 1	Subjects will receive 100 mg acalabrutinib capsule, fasted state;
DRUG	Treatment B- Part 1	Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fasted state
DRUG	Treatment C - Part 1	Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fed state
DRUG	Treatment D- Part 1	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.
DRUG	Treatment A-Part 2	Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fasted state
DRUG	Treatment B - Part 2	Subjects will receive 100 mg acalabrutinib tablet (Variant 2), fasted state
DRUG	Treatment C - Part 2	Subjects will receive 100 mg acalabrutinib tablet (Variant 3), fasted state
DRUG	Treatment D - Part 2	Subjects will receive 100 mg acalabrutinib solution, (Variant 4), fasted state

Timeline

• Start date: 2020-06-24
• Primary completion: 2021-01-20
• Completion: 2021-01-20
• First posted: 2020-07-27
• Last updated: 2021-02-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study