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
Condition: Bioavailability; B-cell Lymphoid Cancer
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Treatment A- Part 1; Treatment B- Part 1; Treatment C - Part 1; Treatment D- Part 1; Treatment A-Part 2; Treatment B - Part 2; Treatment C - Part 2; Treatment D - Part 2
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Subjects will receive 100 mg acalabrutinib capsule, fasted state;; Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fasted state; Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fed state; 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.; Subjects will receive 100 mg acalabrutinib tablet (Variant 1), fasted state; Subjects will receive 100 mg acalabrutinib tablet (Variant 2), fasted state; Subjects will receive 100 mg acalabrutinib tablet (Variant 3), fasted state; Subjects will receive 100 mg acalabrutinib solution, (Variant 4), fasted state
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bruton tyrosine kinase (BTK) inhibitor; Proton Pump Inhibitor (Rabeprazole) Effect; Food Effect; Particle Size Effect