A Study in Healthy Subjects to Assess Bioavailability (Proportion of a Drug Which Enters the Circulation to Have an Active Effect) of Acalabrutinib Tablet and Protonpump Inhibitor Effect (Members of a Class of Medications That Inhibits in Gastric Acid Production) for Rabeprazole
Condition: Mantle Cell Lymphoma; COVID-19
MeSH terms: Lymphoma, Mantle-Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      This Phase 1 study is being conducted to support the clinical development of acalabrutinib in
      hospitalized patients who are unable to swallow acalabrutinib tablet or capsule due to
      respiratory failure, eg, they may require endotracheal intubation for ventilator support and
      nasogastric (NG) tube placement, and it is important to have a clinically acceptable method
      to administer acalabrutinib via NG tube.

      Part 1 of the study is designed to evaluate relative bioavailability by comparing the
      pharmacokinetic (PK) of AT suspension in water administered via NG tube with the PK of
      acalabrutinib capsule suspension in flat COCA-COLA administered via NG tube. Additionally,
      the PPI effect will be evaluated by comparing the PK of AT suspension in water administered
      via NG tube plus rabeprazole with the PK of AT suspension in water administered via NG tube.

      Part 2 of the study is designed to evaluate the effect of NG administration on AT by
      comparing the PK of AT suspension in water administered via NG tube with the PK of AT orally
      administered with water.
    

Detailed description: 
      Part 1 of the study comprises:

        -  A screening period of maximum 28 days.

        -  Three treatment periods during which subjects will reside in the Clinical Unit from Day
           -2, Treatment Period 1 until at least 48 hours after dosing on Day 1, Treatment Period
           3, ie, subjects will be discharged the morning of Day 3, Treatment Period 3.

        -  A Follow-up Visit within 7 to 10 days after the last dose of acalabrutinib.

      There will be a minimum washout period of 4 days between treatment periods. Up to 20 subjects
      will be included to ensure at least 16 subjects are evaluable. Subjects will be randomized to
      one of 2 treatment sequences (ABC, BAC) and each subject will receive single doses of 3
      treatments under fasted conditions.

      Part 2 of the study comprises:

        -  A screening period of maximum 28 days.

        -  Two treatment periods during which subjects will reside in the Clinical Unit from Day
           -2, Treatment Period 1 until at least 48 hours after dosing on Day 1, Treatment Period
           2, ie, subjects will be discharged the morning of Day 3, Treatment Period 2.

        -  A Follow-up Visit within 7 to 10 days after the last dose of acalabrutinib.

      There will be a minimum washout period of 4 days between treatment periods. Up to 20 subjects
      will be included to ensure at least 16 subjects are evaluable. Subjects will be randomized to
      one of 2 treatment sequences (DA, AD) and each subject will receive single doses of 2
      treatments under fasted conditions.
    

Intervention name(s): Acalabrutinib Treatment A; Acalabrutinib Treatment B; Acalabrutinib Treatment C; Acalabrutinib Treatment D
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Participants will receive 100 mg AT suspension in water via NG tube.; Participants will receive 100 mg acalabrutinib capsule suspension via NG tube.; Participants will receive 100 mg AT suspension in water via NG administration plus 20 mg rabeprazole.; Participants will receive 100 mg AT orally.
Other intervention name(s): AT; Acalabrutinib capsule; AT and Pariet® (raberprazole); AT
Intervention MeSH terms: Acalabrutinib
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sequential; Proton-pump Inhibitor; Relative Bioavailability; Bruton Tyrosine Kinase Inhibitor