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Acalabrutinib

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Part 1: Participants will receive Treatment A (100 mg AT suspension in water via NG administration) in Period 1, Treatment B (100 mg acalabrutinib capsule suspension via NG administration) in Period 2, and Treatment C (100 mg AT suspension in water via NG administration plus 20 mg rabeprazole) in Period 3.

Part 2: Participants will receive Treatment D (100 mg AT suspension in water via NG administration) in Period 1 and Treatment A in Period 2.

Part 1: Participants will receive Treatment B in Period 1, Treatment A in Period 2, and Treatment C in Period 3.

Part 2: Participants will receive Treatment A in Period 1 and Treatment D in Period 2.

Participants will receive 100 mg AT suspension in water via NG tube.

Acalabrutinib Treatment A

Participants will receive 100 mg acalabrutinib capsule suspension via NG tube.

Acalabrutinib Treatment B

Participants will receive 100 mg AT suspension in water via NG administration plus 20 mg rabeprazole.

Acalabrutinib Treatment C

Participants will receive 100 mg AT orally.

Acalabrutinib Treatment D

Dr. Rainard Fuhr

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.

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.

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

A 2-Part, Phase I, Open-label, Single-dose, Sequential, Randomized, Crossover Study of Acalabrutinib Tablet Suspension Delivered Via Nasogastric Tube in Healthy Subjects to Evaluate Relative Bioavailability and Proton-pump Inhibitor (Rabeprazole) Effect

Qualified researchers can request access to anonymized individual patient-level data from

AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Part 1: Comparison of AUCinf of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of AUCinf of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of AUClast of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of AUClast of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of Cmax of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of Cmax of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of AUC0-24 of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of AUC0-24 of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of tmax of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of tmax of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of t1/2 of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of t1/2 of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of MRT of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of MRT of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of λz of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of λz of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of CL/F of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of CL/F of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of Vz/F of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of Vz/F of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of M:P\[AUC\] of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of M:P\[AUC\] of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: Comparison of M:P\[Cmax\] of acalabrutinib and its metabolite (ACP-5862) following NG administration of AT suspension versus NG administration of acalabrutinib capsule suspension and to evaluate the effect of PPI (rabeprazole) on acalabrutinib and ACP-5862 PK profiles following NG administration of AT suspension.

Part 2: Comparison of M:P\[Cmax\] of acalabrutinib and ACP 5862 following NG administration of AT suspension versus oral administration of AT.

Part 1: To evaluate the safety and tolerability of AT suspension administered via NG tube and to evaluate the safety and tolerability of AT suspension via NG tube when co-administered with rabeprazole.

Part 2: To evaluate the safety and tolerability of AT, administered orally.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT04564040	Mantle Cell Lym... COVID-19	Acalabrutinib T... Acalabrutinib T... Acalabrutinib T... Acalabrutinib T...	18 Years - 55 Years	AstraZeneca
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	NCT04564040	Mantle Cell Lym... COVID-19	Acalabrutinib T... Acalabrutinib T... Acalabrutinib T... Acalabrutinib T...	18 Years - 55 Years	AstraZeneca

Spots Global Cancer Trial Database for acalabrutinib treatment b