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

Study identifier:D8220C00018

ClinicalTrials.gov identifier:NCT04488016

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

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

Medical condition

Bioavailability

Phase

Phase 1

Healthy volunteers

Yes

Study drug

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

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 24 Jun 2020

Primary Completion Date: 20 Jan 2021

Study Completion Date: 20 Jan 2021

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jun 2022 by AstraZeneca

Collaborators

Acerta Pharma

Inclusion and exclusion criteria

Inclusion Criteria

1 Provision of signed and dated, written informed consent prior to any study specific procedures.
2 Healthy adult male or female subjects aged 18 – 55 years with suitable veins for cannulation or repeated venipuncture.
3 Male subject must adhere to the contraception methods.
4 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.
5 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.
6 Understands the study procedures in the Informed Consent Form (ICF) and willing and able to comply with the protocol.
7 Willingness and ability to swallow study drugs, including the SmartPill.
8 Willingness to consume a standardized, high- calorie, high-fat FDA breakfast.

Exclusion Criteria

1 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.
2 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.
3 Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections).
4 Any clinically significant illness, medical/surgical procedure, or trauma within 30 days of
the first administration of IMP.
5 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.
6 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.
7 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.
8 Any positive result on screening for serum hepatitis B surface antigen, hepatitis B core antibody (anti-HBc), hepatitis C antibody, and HIV antibody.
9 Known or suspected history of drug abuse, as judged by the PI.
10 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.
The period of exclusion begins 90 days after the final dose or 30 days after the last visitwhichever is the longest.
11 Plasma donation within 30 days of screening or any blood donation/loss more than 500 mL during the 90 days prior to screening.
12 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.
13 Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 90 days prior to screening.
14 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.
15 Use of drugs with enzyme-inducing properties such as St John’s Wort within 3 weeks prior to the first administration of IMP.
16 Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life. Hormone replacement therapy will not be allowed.
17 Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI.
18 Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate) as judged by the PI. Excessive intake of caffeine defined as the regular consumption of more than 600 mg of caffeine per day (e.g., >5 cups of coffee) or would likely be unable to
refrain from the use of caffeine-containing beverages during confinement at the investigational site.
19 Part 1 only: Inability or unwillingness to swallow SmartPill, including:
Subject has any of the following contraindications for the SmartPill:
(1) A history of gastric bezoars
(2) Swallowing disorders
(3) Suspected or known strictures, fistulas or physiological/mechanical GI obstruction
(4) History of GI surgery within 90 days of administration
(5) Severe dysphagia to food or pills
(6) Crohn’s disease or diverticulitis
(7) Cardiac pacemakers or other implanted electromedical devices
20 Involvement of any AstraZeneca, Acerta Pharma, Parexel or study site employee or their
close relatives.
21 Subjects who have previously received acalabrutinib.
22 Judgment by the PI that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with
study procedures, restrictions, and requirements.
23 Subjects who cannot communicate reliably with the Investigator.
24 Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

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.

Location

Research Site

Baltimore, MD, United States, 21225

Arms	Assigned Interventions
Experimental: Cohort 1 -Part 1 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 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
Experimental: Cohort 2- Part 1 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 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
Experimental: Cohort 3- Part 1 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 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.
Experimental: Cohort 4 - Part 1 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 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.
Experimental: Cohort 1- Part 2 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 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
Experimental: Cohort 2 - Part 2 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 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

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted in approximately 28 subjects for Part 1 and 24 subjects for Part 2 at one study centers in the Parexel Early Phase Clinical Unit - Baltimore from 24 Jun 2020 (first subject first visit) to 20 Jan 2021 (last subject last visit).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The screening period was of 28 days. All the study assessments were performed as per the schedule of assessment.

Reporting Groups

	Description
Part 1: Treatment sequence ABC	Subjects received single oral dose of acalabrutinib on 3 occasions [Treatment A: SmartPill/ 100 mg acalabrutinib capsule, fasted state; Treatment B: SmartPill/ 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment C: 100 mg acalabrutinib maleate tablet (Variant 1), fed state], separated by at least 7 days washout, under fasted and fed conditions.
Part 1: Treatment sequence BAC	Subjects received single oral dose of acalabrutinib on 3 occasions [Treatment B: SmartPill/ 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment A: SmartPill/ 100 mg acalabrutinib capsule, fasted state; Treatment C: 100 mg acalabrutinib maleate tablet (Variant 1), fed state], separated by at least 7 days washout, under fasted and fed conditions.
Part 1: Treatment sequence ABD	Subjects received single oral dose of acalabrutinib on 3 occasions [Treatment A: SmartPill/ 100 mg acalabrutinib capsule, fasted state; Treatment B: SmartPill/ 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment D: 20 mg rabeprazole × 1 (fasted) at 2 hours before administration of 100 mg acalabrutinib maleate tablet (Variant 1) and following prior administration of 20 mg rabeprazole BID (with meals) on Days -3, -2, and -1], separated by at least 7 days washout, under fasted and fed conditions.
Part 1 : Treatment sequence BAD	Subjects received single oral dose of acalabrutinib on 3 occasions [Treatment B: SmartPill/ 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment A: SmartPill/ 100 mg acalabrutinib capsule, fasted state; Treatment D: 20 mg rabeprazole × 1 (fasted) at 2 hours before administration of 100 mg acalabrutinib maleate tablet (Variant 1) and following prior administration of 20 mg rabeprazole BID (with meals) on Days -3, -2, and -1], separated by at least 7 days washout, under fasted and fed conditions.
Part 2: Treatment sequence ABCD	Subjects received single oral dose of acalabrutinib on 4 occasions [Treatment A: 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment B: 100 mg acalabrutinib maleate tablet (Variant 2), fasted state; Treatment C: 100 mg acalabrutinib maleate tablet (Variant 3), fasted state; Treatment D: 100 mg acalabrutinib solution, fasted state], separated by at least 3 days washout, under fasted conditions.
Part 2: Treatment sequence BADC	Subjects received single oral dose of acalabrutinib on 4 occasions [Treatment B: 100 mg acalabrutinib maleate tablet (Variant 2), fasted state; Treatment A: 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment D: 100 mg acalabrutinib solution, fasted state; Treatment C: 100 mg acalabrutinib maleate tablet (Variant 3), fasted state], separated by at least 3 days washout, under fasted conditions.

Participant Flow: Overall Study

	Part 1: Treatment sequence ABC	Part 1: Treatment sequence BAC	Part 1: Treatment sequence ABD	Part 1 : Treatment sequence BAD	Part 2: Treatment sequence ABCD	Part 2: Treatment sequence BADC
STARTED	8	8	7	7	12	12
COMPLETED	7	8	7	7	12	10
NOT COMPLETED	1	0	0	0	0	2
Lost to Follow-up	1	0	0	0	0	2

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The randomized set consisted of all subjects randomized into the study.

Reporting Groups

	Description
Part 1: Treatment sequence ABC	Subjects received single oral dose of acalabrutinib on 3 occasions [Treatment A: SmartPill/ 100 mg acalabrutinib capsule, fasted state; Treatment B: SmartPill/ 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment C: 100 mg acalabrutinib maleate tablet (Variant 1), fed state], separated by at least 7 days washout, under fasted and fed conditions.
Part 1: Treatment sequence BAC	Subjects received single oral dose of acalabrutinib on 3 occasions [Treatment B: SmartPill/ 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment A: SmartPill/ 100 mg acalabrutinib capsule, fasted state; Treatment C: 100 mg acalabrutinib maleate tablet (Variant 1), fed state], separated by at least 7 days washout, under fasted and fed conditions.
Part 1: Treatment sequence ABD	Subjects received single oral dose of acalabrutinib on 3 occasions [Treatment A: SmartPill/ 100 mg acalabrutinib capsule, fasted state; Treatment B: SmartPill/ 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment D: 20 mg rabeprazole × 1 (fasted) at 2 hours before administration of 100 mg acalabrutinib maleate tablet (Variant 1) and following prior administration of 20 mg rabeprazole BID (with meals) on Days -3, -2, and -1], separated by at least 7 days washout, under fasted and fed conditions.
Part 1 : Treatment sequence BAD	Subjects received single oral dose of acalabrutinib on 3 occasions [Treatment B: SmartPill/ 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment A: SmartPill/ 100 mg acalabrutinib capsule, fasted state; Treatment D: 20 mg rabeprazole × 1 (fasted) at 2 hours before administration of 100 mg acalabrutinib maleate tablet (Variant 1) and following prior administration of 20 mg rabeprazole BID (with meals) on Days -3, -2, and -1], separated by at least 7 days washout, under fasted and fed conditions.
Part 2: Treatment sequence ABCD	Subjects received single oral dose of acalabrutinib on 4 occasions [Treatment A: 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment B: 100 mg acalabrutinib maleate tablet (Variant 2), fasted state; Treatment C: 100 mg acalabrutinib maleate tablet (Variant 3), fasted state; Treatment D: 100 mg acalabrutinib solution, fasted state], separated by at least 3 days washout, under fasted conditions.
Part 2: Treatment sequence BADC	Subjects received single oral dose of acalabrutinib on 4 occasions [Treatment B: 100 mg acalabrutinib maleate tablet (Variant 2), fasted state; Treatment A: 100 mg acalabrutinib maleate tablet (Variant 1), fasted state; Treatment D: 100 mg acalabrutinib solution, fasted state; Treatment C: 100 mg acalabrutinib maleate tablet (Variant 3), fasted state], separated by at least 3 days washout, under fasted conditions.

Baseline Measures

	Part 1: Treatment sequence ABC	Part 1: Treatment sequence BAC	Part 1: Treatment sequence ABD	Part 1 : Treatment sequence BAD	Part 2: Treatment sequence ABCD	Part 2: Treatment sequence BADC	Total
Number of Participants [units: Participants]	8	8	7	7	12	12	54
Sex: Female, Male [units: ]
Female	1	0	2	2	2	1	8
Male	7	8	5	5	10	11	46
Age Continuous [units: Years] Mean ± Standard Deviation	37.5 ± 10.2	44.0 ± 9.3	42.7 ± 9.1	41.4 ± 8.7	37.0 ± 8.3	40.9 ± 10.5	NA ± NA ^[1]
Race/Ethnicity, Customized [units: ]
White	3	4	5	3	3	6	24
Black or African American	5	3	2	4	9	6	29
Asian	0	1	0	0	0	0	1
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	1	5	0	2	2	3	13
Not Hispanic or Latino	7	3	7	5	10	9	41
Unknown or Not Reported	0	0	0	0	0	0	0

Outcome Measures

1. Primary Outcome Measure: Maximum observed plasma concentration (Cmax) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Primary
Measure Name	Maximum observed plasma concentration (Cmax)
Measure Description	The Cmax was assessed as Pharmakokinetics (PK) of Acalabrutinib. The relative bioavailability of the acalabrutinib maleate tablet compared with acalabrutinib capsules in fasted state was assessed. The impact of drug substance particle size on the bioavailability of acalabrutinib maleate tablets was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or Adverse events (AEs) considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Maximum observed plasma concentration (Cmax) [units: nanogram/milliliter (ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	541.6 (41.06%)	504.9 (49.88%)	255.6 (46.52%)	371.9 (81.44%)	596.5 (44.29%)	543.3 (56.12%)	602.2 (60.51%)	727.2 (44.90%)

Statistical Analysis 1 for Maximum observed plasma concentration (Cmax)

Groups^[1]	Part 1: Treatment A, Part 1: Treatment B
Method^[3]	ANOVA
Other^[5]	90.50
90% Confidence Interval	( 79.42 to 103.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	Geometric mean ratio and corresponding 90% CI are back-transformed and presented as percentages.

Statistical Analysis 2 for Maximum observed plasma concentration (Cmax)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment D
Method^[3]	ANOVA
Other^[5]	121.9
90% Confidence Interval	( 106.7 to 139.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Maximum observed plasma concentration (Cmax)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment B
Method^[3]	ANOVA
Other^[5]	91.08
90% Confidence Interval	( 79.35 to 104.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Maximum observed plasma concentration (Cmax)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment C
Method^[3]	ANOVA
Other^[5]	100.2
90% Confidence Interval	( 82.95 to 121.0 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Maximum observed plasma concentration (Cmax)

Groups^[1]	Part 2: Treatment B, Part 2: Treatment C
Method^[3]	ANOVA
Other^[5]	111.8
90% Confidence Interval	( 90.67 to 137.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Primary
Measure Name	Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)
Measure Description	The AUClast was assessed as PK of Acalabrutinib. The relative bioavailability of the acalabrutinib maleate tablet compared with acalabrutinib capsules in fasted state was assessed. The impact of drug substance particle size on the bioavailability of acalabrutinib maleate tablets was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) [units: hour.nanogram/milliliter (h·ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	565.7 (25.41%)	556.2 (34.73%)	525.7 (18.34%)	669.7 (40.54%)	662.9 (33.27%)	612.8 (33.21%)	628.7 (30.14%)	673.5 (36.99%)

Statistical Analysis 1 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Part 1: Treatment A, Part 1: Treatment B
Method^[3]	ANOVA
Other^[5]	98.05
90% Confidence Interval	( 91.77 to 104.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	Geometric mean ratio and corresponding 90% CI are back-transformed and presented as percentages.

Statistical Analysis 2 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment D
Method^[3]	ANOVA
Other^[5]	101.6
90% Confidence Interval	( 95.32 to 108.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment B
Method^[3]	ANOVA
Other^[5]	92.46
90% Confidence Interval	( 85.72 to 99.72 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment C
Method^[3]	ANOVA
Other^[5]	93.71
90% Confidence Interval	( 85.35 to 102.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)

Groups^[1]	Part 2: Treatment B, Part 2: Treatment C
Method^[3]	ANOVA
Other^[5]	101.3
90% Confidence Interval	( 94.08 to 109.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Primary Outcome Measure: Area under plasma concentration-time curve from time zero to infinity (AUCinf) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Primary
Measure Name	Area under plasma concentration-time curve from time zero to infinity (AUCinf)
Measure Description	The AUCinf was assessed as PK of Acalabrutinib. The relative bioavailability of the acalabrutinib maleate tablet compared with acalabrutinib capsules in fasted state was assessed. The impact of drug substance particle size on the bioavailability of acalabrutinib maleate tablets was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Area under plasma concentration-time curve from time zero to infinity (AUCinf) [units: hour.nanogram/milliliter (h·ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	569.9 (25.55%)	559.5 (34.63%)	528.7 (18.20%)	694.1 (39.74%)	667.2 (32.91%)	616.1 (33.01%)	632.7 (30.00%)	677.0 (36.84%)

Statistical Analysis 1 for Area under plasma concentration-time curve from time zero to infinity (AUCinf)

Groups^[1]	Part 1: Treatment A, Part 1: Treatment B
Method^[3]	ANOVA
Other^[5]	97.90
90% Confidence Interval	( 91.62 to 104.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Area under plasma concentration-time curve from time zero to infinity (AUCinf)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment D
Method^[3]	ANOVA
Other^[5]	101.5
90% Confidence Interval	( 95.30 to 108.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Area under plasma concentration-time curve from time zero to infinity (AUCinf)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment B
Method^[3]	ANOVA
Other^[5]	92.35
90% Confidence Interval	( 85.64 to 99.58 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Area under plasma concentration-time curve from time zero to infinity (AUCinf)

Groups^[1]	Part 2: Treatment A, Part 2: Treatment C
Method^[3]	ANOVA
Other^[5]	93.68
90% Confidence Interval	( 85.37 to 102.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 5 for Area under plasma concentration-time curve from time zero to infinity (AUCinf)

Groups^[1]	Part 2: Treatment B, Part 2: Treatment C
Method^[3]	ANOVA
Other^[5]	101.4
90% Confidence Interval	( 94.20 to 109.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Maximum observed plasma concentration (Cmax) for Acalabrutinib [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Maximum observed plasma concentration (Cmax) for Acalabrutinib
Measure Description	The Cmax was assessed as PK of Acalabrutinib. The effects of proton pump inhibitor rabeprazole on acalabrutinib PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed was assessed. The effect of food on acalabrutinib PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Maximum observed plasma concentration (Cmax) for Acalabrutinib [units: nanogram/milliliter (ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	541.6 (41.06%)	504.9 (49.88%)	255.6 (46.52%)	371.9 (81.44%)	596.5 (44.29%)	543.3 (56.12%)	602.2 (60.51%)	727.2 (44.90%)

Statistical Analysis 1 for Maximum observed plasma concentration (Cmax) for Acalabrutinib

Groups^[1]	Part 1: Treatment B, Part 1: Treatment D
Method^[3]	ANOVA
Other^[5]	76.39
90% Confidence Interval	( 54.88 to 106.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	Geometric mean ratio and corresponding 90% CI are back-transformed and presented as percentages.

Statistical Analysis 2 for Maximum observed plasma concentration (Cmax) for Acalabrutinib

Groups^[1]	Part 1: Treatment B, Part 1: Treatment C
Method^[3]	ANOVA
Other^[5]	46.01
90% Confidence Interval	( 35.92 to 58.95 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for Acalabrutinib [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for Acalabrutinib
Measure Description	The AUClast was assessed as PK of Acalabrutinib. The effects of proton pump inhibitor rabeprazole on acalabrutinib PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for Acalabrutinib [units: hour.nanogram/milliliter (h·ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	565.7 (25.41%)	556.2 (34.73%)	525.7 (18.34%)	669.7 (40.54%)	662.9 (33.27%)	612.8 (33.21%)	628.7 (30.14%)	673.5 (36.99%)

Statistical Analysis 1 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for Acalabrutinib

Groups^[1]	Part 1: Treatment B, Part 1: Treatment D
Method^[3]	ANOVA
Other^[5]	113.9
90% Confidence Interval	( 101.4 to 128.0 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	Geometric mean ratio and corresponding 90% CI are back-transformed and presented as percentages.

Statistical Analysis 2 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for Acalabrutinib

Groups^[1]	Part 1: Treatment B, Part 1: Treatment C
Method^[3]	ANOVA
Other^[5]	97.69
90% Confidence Interval	( 87.18 to 109.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Area under plasma concentration-time curve from time zero to infinity (AUCinf) for Acalabrutinib [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve from time zero to infinity (AUCinf) for Acalabrutinib
Measure Description	The AUCinf was assessed as PK of Acalabrutinib. The effects of proton pump inhibitor rabeprazole on acalabrutinib PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Area under plasma concentration-time curve from time zero to infinity (AUCinf) for Acalabrutinib [units: hour.nanogram/milliliter (h·ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	569.9 (25.55%)	559.5 (34.63%)	528.7 (18.20%)	694.1 (39.74%)	667.2 (32.91%)	616.1 (33.01%)	632.7 (30.00%)	677.0 (36.84%)

Statistical Analysis 1 for Area under plasma concentration-time curve from time zero to infinity (AUCinf) for Acalabrutinib

Groups^[1]	Part 1: Treatment B, Part 1: Treatment D
Method^[3]	ANOVA
Other^[5]	117.4
90% Confidence Interval	( 105.4 to 130.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Area under plasma concentration-time curve from time zero to infinity (AUCinf) for Acalabrutinib

Groups^[1]	Part 1: Treatment B, Part 1: Treatment C
Method^[3]	ANOVA
Other^[5]	97.69
90% Confidence Interval	( 87.19 to 109.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Maximum observed plasma concentration (Cmax) for ACP-5862 [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Maximum observed plasma concentration (Cmax) for ACP-5862
Measure Description	The Cmax was assessed as ACP-5862 PK profile of the acalabrutinib maleate tablet compared with acalabrutinib capsule in fasted state. The effects of proton pump inhibitor rabeprazole on acalabrutinib metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Maximum observed plasma concentration (Cmax) for ACP-5862 [units: nanogram/milliliter (ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	533.7 (37.21%)	538.5 (42.19%)	358.4 (33.19%)	365.3 (56.45%)	536.5 (39.38%)	532.8 (33.25%)	594.5 (33.65%)	662.6 (26.54%)

Statistical Analysis 1 for Maximum observed plasma concentration (Cmax) for ACP-5862

Groups^[1]	Part 1: Treatment B, Part 1: Treatment D
Method^[3]	ANOVA
Other^[5]	69.76
90% Confidence Interval	( 51.31 to 94.86 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Maximum observed plasma concentration (Cmax) for ACP-5862

Groups^[1]	Part 1: Treatment B, Part 1: Treatment C
Method^[3]	ANOVA
Other^[5]	63.94
90% Confidence Interval	( 54.15 to 75.49 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Maximum observed plasma concentration (Cmax) for ACP-5862

Groups^[1]	Part 1: Treatment A, Part 1: Treatment B
Method^[3]	ANOVA
Other^[5]	99.84
90% Confidence Interval	( 91.94 to 108.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Maximum observed plasma concentration (Cmax) for ACP-5862

Groups^[1]	Part 2: Treatment A, Part 2: Treatment D
Method^[3]	ANOVA
Other^[5]	123.5
90% Confidence Interval	( 109.9 to 138.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for ACP-5862 [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for ACP-5862
Measure Description	The AUClast was assessed as ACP-5862 PK profile of the acalabrutinib maleate tablet compared with acalabrutinib capsule in fasted state. The effects of proton pump inhibitor rabeprazole on acalabrutinib metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for ACP-5862 [units: hour.nanogram/milliliter (h·ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	1534 (24.58%)	1575 (25.87%)	1532 (17.36%)	1656 (29.58%)	1653 (24.97%)	1674 (25.69%)	1702 (26.03%)	1762 (27.08%)

Statistical Analysis 1 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for ACP-5862

Groups^[1]	Part 1: Treatment B, Part 1: Treatment D
Method^[3]	ANOVA
Other^[5]	99.40
90% Confidence Interval	( 90.81 to 108.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for ACP-5862

Groups^[1]	Part 1: Treatment B, Part 1: Treatment C
Method^[3]	ANOVA
Other^[5]	100.1
90% Confidence Interval	( 95.47 to 104.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for ACP-5862

Groups^[1]	Part 1: Treatment A, Part 1: Treatment B
Method^[3]	ANOVA
Other^[5]	103.3
90% Confidence Interval	( 99.86 to 106.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) for ACP-5862

Groups^[1]	Part 2: Treatment A, Part 2: Treatment D
Method^[3]	ANOVA
Other^[5]	106.6
90% Confidence Interval	( 103.2 to 110.2 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

9. Secondary Outcome Measure: Area under plasma concentration-time curve from time zero to infinity (AUCinf) for ACP-5862 [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve from time zero to infinity (AUCinf) for ACP-5862
Measure Description	The AUCinf was assessed as ACP-5862 PK profile of the acalabrutinib maleate tablet compared with acalabrutinib capsule in fasted state. The effects of proton pump inhibitor rabeprazole on acalabrutinib metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Area under plasma concentration-time curve from time zero to infinity (AUCinf) for ACP-5862 [units: hour.nanogram/milliliter (h·ng/mL)] Geometric Mean (Geometric Coefficient of Variation)	1625 (24.14%)	1672 (24.84%)	1644 (17.13%)	1783 (28.71%)	1746 (24.46%)	1775 (24.80%)	1792 (25.78%)	1845 (26.79%)

Statistical Analysis 1 for Area under plasma concentration-time curve from time zero to infinity (AUCinf) for ACP-5862

Groups^[1]	Part 1: Treatment B, Part 1: Treatment D
Method^[3]	ANOVA
Other^[5]	100.7
90% Confidence Interval	( 93.26 to 108.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Area under plasma concentration-time curve from time zero to infinity (AUCinf) for ACP-5862

Groups^[1]	Part 1: Treatment B, Part 1: Treatment C
Method^[3]	ANOVA
Other^[5]	101.7
90% Confidence Interval	( 96.90 to 106.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Area under plasma concentration-time curve from time zero to infinity (AUCinf) for ACP-5862

Groups^[1]	Part 1: Treatment A, Part 1: Treatment B
Method^[3]	ANOVA
Other^[5]	103.6
90% Confidence Interval	( 100.1 to 107.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, period, treatment as fixed effect, and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Area under plasma concentration-time curve from time zero to infinity (AUCinf) for ACP-5862

Groups^[1]	Part 2: Treatment A, Part 2: Treatment D
Method^[3]	ANOVA
Other^[5]	105.7
90% Confidence Interval	( 102.7 to 108.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Result based on linear mixed effect ANOVA of log transformed PK parameter with sequence, treatment as fixed effect; and subject nested within sequence as random effect.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

10. Secondary Outcome Measure: Area under the plasma concentration-time curve from time zero to 12 hours post-dose (AUC0-12) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve from time zero to 12 hours post-dose (AUC0-12)
Measure Description	The AUC0-12 was assessed as PK profile of Acalabrutinib and ACP-5862. The effects of proton pump inhibitor rabeprazole on acalabrutinib and its metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib and its metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Area under the plasma concentration-time curve from time zero to 12 hours post-dose (AUC0-12) [units: hournanogram/milliliter (hng/mL)] Mean (Standard Deviation)
Acalabrutinib	583.9 (144.5)	589.8 (205.0)	535.3 (97.69)	713.7 (289.4)	698.5 (227.8)	647.3 (226.0)	659.8 (227.6)	718.8 (271.0)
ACP-5862	1427 (333.1)	1475 (369.7)	1356 (235.1)	1503 (498.7)	1532 (436.5)	1553 (425.3)	1582 (447.5)	1665 (474.2)

No statistical analysis provided for Area under the plasma concentration-time curve from time zero to 12 hours post-dose (AUC0-12)

11. Secondary Outcome Measure: Extrapolated area under the curve from tlast to infinity, expressed as percentage of AUCinf (AUCextrap) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Extrapolated area under the curve from tlast to infinity, expressed as percentage of AUCinf (AUCextrap)
Measure Description	The AUCextrap was assessed as PK profile of Acalabrutinib and ACP-5862. The effects of proton pump inhibitor rabeprazole on acalabrutinib and its metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib and its metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Extrapolated area under the curve from tlast to infinity, expressed as percentage of AUCinf (AUCextrap) [units: Percentage (%)] Mean (Standard Deviation)
Acalabrutinib	0.7355 (0.7531)	0.5834 (0.2413)	0.5671 (0.2516)	3.073 (8.611)	0.6465 (0.6413)	0.5335 (0.2446)	0.6262 (0.3222)	0.5278 (0.2728)
ACP-5862	5.607 (1.385)	5.826 (1.893)	6.783 (2.648)	7.095 (3.050)	5.298 (1.527)	5.633 (2.466)	4.975 (1.439)	4.500 (1.038)

No statistical analysis provided for Extrapolated area under the curve from tlast to infinity, expressed as percentage of AUCinf (AUCextrap)

12. Secondary Outcome Measure: Half-life associated with terminal slope of a semi-logarithmic concentration-time curve (t½) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Half-life associated with terminal slope of a semi-logarithmic concentration-time curve (t½)
Measure Description	The t½ was assessed as PK profile of Acalabrutinib and ACP-5862. The effects of proton pump inhibitor rabeprazole on acalabrutinib and its metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib and its metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Half-life associated with terminal slope of a semi-logarithmic concentration-time curve (t½) [units: hour (h)] Mean (Standard Deviation)
Acalabrutinib	1.954 (2.031)	1.515 (0.6280)	1.347 (0.3991)	2.863 (2.313)	1.768 (0.7369)	1.364 (0.4352)	1.794 (0.7305)	1.685 (0.7755)
ACP-5862	7.824 (1.558)	8.152 (1.287)	7.945 (1.439)	7.848 (1.579)	7.668 (1.035)	7.856 (1.755)	7.406 (1.005)	7.130 (1.145)

No statistical analysis provided for Half-life associated with terminal slope of a semi-logarithmic concentration-time curve (t½)

13. Secondary Outcome Measure: Time to reach maximum observed concentration (tmax) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Time to reach maximum observed concentration (tmax)
Measure Description	The tmax was assessed as PK profile of Acalabrutinib and ACP-5862. The effects of proton pump inhibitor rabeprazole on acalabrutinib and its metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib and its metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Time to reach maximum observed concentration (tmax) [units: hour (h)] Median (Full Range)
Acalabrutinib	0.75 (0.48 to 2.02)	0.73 (0.25 to 1.53)	2.00 (0.25 to 4.00)	1.01 (0.23 to 3.00)	0.50 (0.25 to 1.50)	0.75 (0.25 to 3.00)	0.50 (0.25 to 2.00)	0.50 (0.25 to 1.00)
ACP-5862	1.00 (0.73 to 3.00)	0.80 (0.50 to 2.98)	2.98 (0.98 to 4.02)	1.75 (0.52 to 6.00)	0.77 (0.48 to 2.02)	0.88 (0.50 to 3.00)	0.75 (0.48 to 3.50)	0.74 (0.48 to 1.52)

No statistical analysis provided for Time to reach maximum observed concentration (tmax)

14. Secondary Outcome Measure: Apparent total body clearance of drug from plasms after extravascular administration (acalabrutinib only) (CL/F) (parent only) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Apparent total body clearance of drug from plasms after extravascular administration (acalabrutinib only) (CL/F) (parent only)
Measure Description	The CL/F was assessed as PK profile of Acalabrutinib. The effects of proton pump inhibitor rabeprazole on acalabrutinib PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Apparent total body clearance of drug from plasms after extravascular administration (acalabrutinib only) (CL/F) (parent only) [units: Liter/hour (L/h)] Mean (Standard Deviation)	180.9 (46.45)	188.7 (64.41)	192.0 (34.22)	154.4 (61.75)	157.4 (49.95)	170.4 (54.44)	164.1 (42.61)	156.9 (57.76)

No statistical analysis provided for Apparent total body clearance of drug from plasms after extravascular administration (acalabrutinib only) (CL/F) (parent only)

15. Secondary Outcome Measure: Apparent volume of distribution during the terminal phase after extravascular administration (acalabrutinib only) (Vz/F) (parent only) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	Apparent volume of distribution during the terminal phase after extravascular administration (acalabrutinib only) (Vz/F) (parent only)
Measure Description	The Vz/F was assessed as PK profile of Acalabrutinib. The effects of proton pump inhibitor rabeprazole on acalabrutinib PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
Apparent volume of distribution during the terminal phase after extravascular administration (acalabrutinib only) (Vz/F) (parent only) [units: Liter (L)] Mean (Standard Deviation)	469.3 (332.5)	386.8 (135.9)	373.9 (134.8)	583.6 (456.9)	400.8 (245.8)	334.8 (193.1)	414.6 (191.8)	378.8 (222.5)

No statistical analysis provided for Apparent volume of distribution during the terminal phase after extravascular administration (acalabrutinib only) (Vz/F) (parent only)

16. Secondary Outcome Measure: ACP-5862 metabolite to parent ratio (M/P) based on AUC (MPAUC) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	ACP-5862 metabolite to parent ratio (M/P) based on AUC (MPAUC)
Measure Description	The MPAUC was assessed as PK profile of ACP-5862. The effects of proton pump inhibitor rabeprazole on acalabrutinib metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
ACP-5862 metabolite to parent ratio (M/P) based on AUC (MPAUC) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	2.756 (21.06%)	2.890 (25.32%)	3.007 (17.89%)	2.484 (22.32%)	2.529 (25.04%)	2.785 (24.62%)	2.738 (25.00%)	2.635 (23.30%)

No statistical analysis provided for ACP-5862 metabolite to parent ratio (M/P) based on AUC (MPAUC)

17. Secondary Outcome Measure: ACP-5862 metabolite to parent ratio (M/P) based on Cmax (MPCmax) [ Time Frame: Part 1 and Part 2: Day 1 and Day 2 of each treatment period ]

Measure Type	Secondary
Measure Name	ACP-5862 metabolite to parent ratio (M/P) based on Cmax (MPCmax)
Measure Description	The MPCmax was assessed as PK profile of ACP-5862. The effects of proton pump inhibitor rabeprazole on acalabrutinib metabolite (ACP-5862) PK profiles obtained after dosing the acalabrutinib maleate tablet was assessed. The effect of food on acalabrutinib metabolite (ACP-5862) PK obtained after dosing the acalabrutinib maleate tablet was assessed.
Time Frame	Part 1 and Part 2: Day 1 and Day 2 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who had at least one quantifiable post dose concentration with no important protocol deviations or AEs considered to have impacted on the analysis of the PK data.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	23	24
ACP-5862 metabolite to parent ratio (M/P) based on Cmax (MPCmax) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	0.9526 (27.67%)	1.031 (32.12%)	1.356 (30.17%)	0.9496 (37.94%)	0.8695 (29.87%)	0.9480 (39.18%)	0.9544 (36.26%)	0.8809 (25.13%)

No statistical analysis provided for ACP-5862 metabolite to parent ratio (M/P) based on Cmax (MPCmax)

18. Secondary Outcome Measure: Number of Subjects with Adverse events (AEs) [ Time Frame: Part 1 and Part 2: From screening (Starting on Day -28) until follow up/ early termination [Part 1: approximately 7 to 8 weeks and Part 2: approximately 6 to 7 weeks] ]

Measure Type	Secondary
Measure Name	Number of Subjects with Adverse events (AEs)
Measure Description	AEs as variables of safety and tolerability of single doses of acalabrutinib maleate tablet in healthy subjects was assesed.
Time Frame	Part 1 and Part 2: From screening (Starting on Day -28) until follow up/ early termination [Part 1: approximately 7 to 8 weeks and Part 2: approximately 6 to 7 weeks]
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set: the safety analysis set for each study part included all subjects who received the dose in Treatment Period 1 and for whom any safety post-dose data were available.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Measured Values

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Number of Participants Analyzed [units:participants]	30	29	14	14	24	24	24	24
Number of Subjects with Adverse events (AEs) [units: Participants]
Any AE	2	5	1	1	0	4	1	4
Any AE with outcome = death	0	0	0	0	0	0	0	0
Any serious adverse event (SAE) (including events with outcome = death)	0	0	0	0	0	0	0	0
Any AE leading to discontinuation of Investigational Medicinal Product (IMP)	1	1	0	0	0	0	0	0
Any AE leading to withdrawal from the study	0	0	0	0	0	0	0	0

No statistical analysis provided for Number of Subjects with Adverse events (AEs)

Serious Adverse Events

Time Frame	Part 1 and Part 2: From screening (Starting on Day -28) until follow up/ early termination [Part 1: approximately 7 to 8 weeks and Part 2: approximately 6 to 7 weeks]
Additional Description	No text entered.

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Serious Adverse Events

	Part 1: Treatment A	Part 1: Treatment B	Part 1: Treatment C	Part 1: Treatment D	Part 2: Treatment A	Part 2: Treatment B	Part 2: Treatment C	Part 2: Treatment D
Total, serious adverse events
# participants affected / at risk	0/30 (0.00%)	0/29 (0.00%)	0/14 (0.00%)	0/14 (0.00%)	0/24 (0.00%)	0/24 (0.00%)	0/24 (0.00%)	0/24 (0.00%)

Other Adverse Events

Time Frame	Part 1 and Part 2: From screening (Starting on Day -28) until follow up/ early termination [Part 1: approximately 7 to 8 weeks and Part 2: approximately 6 to 7 weeks]
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Part 1: Treatment A	Subjects will receive single oral dose of acalabrutinib capsule in fasted condition.
Part 1: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 1: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fed condition.
Part 1: Treatment D	Subjects will receive rabeprazole × 1 (fasted) at 2 hours before administration of acalabrutinib maleate tablet (Variant 1) and following prior administration of rabeprazole twice a daily (with meals) on Days -3, -2, and -1.
Part 2: Treatment A	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment B	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 1) in fasted condition.
Part 2: Treatment C	Subjects will receive single oral dose of acalabrutinib maleate tablet (Variant 3) in fasted condition.
Part 2: Treatment D	Subjects will receive single oral dose of acalabrutinib solution in fasted condition.

Other Adverse Events

Part 1: Treatment A

Part 1: Treatment B

Part 1: Treatment C

Part 1: Treatment D

Part 2: Treatment A

Part 2: Treatment B

Part 2: Treatment C

Part 2: Treatment D

Total, other (not including serious) adverse events

# participants affected / at risk

2/30 (6.67%)

5/29 (17.24%)

1/14 (7.14%)

0/24 (0.00%)

4/24 (16.67%)

1/24 (4.17%)

4/24 (16.67%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

1/14 (7.14%)

0/24 (0.00%)

1/24 (4.17%)

Gastrointestinal disorders

Gastrooesophageal reflux disease¹

# participants affected / at risk

0/30 (0.00%)

1/29 (3.45%)

0/14 (0.00%)

0/24 (0.00%)

Nervous system disorders

Headache¹

# participants affected / at risk

0/30 (0.00%)

2/29 (6.90%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

Respiratory, thoracic and mediastinal disorders

Throat irritation¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

1/14 (7.14%)

0/14 (0.00%)

0/24 (0.00%)

Respiratory, thoracic and mediastinal disorders

Upper-airway cough syndrome¹

# participants affected / at risk

1/30 (3.33%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

0/30 (0.00%)

1/29 (3.45%)

0/14 (0.00%)

0/24 (0.00%)

Skin and subcutaneous tissue disorders

Rash pruritic¹

# participants affected / at risk

1/30 (3.33%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

Injury, poisoning and procedural complications

Traumatic haematoma¹

# participants affected / at risk

0/30 (0.00%)

1/29 (3.45%)

0/14 (0.00%)

0/24 (0.00%)

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

0/30 (0.00%)

1/29 (3.45%)

0/14 (0.00%)

0/24 (0.00%)

Gastrointestinal disorders

Gingival pain¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

General disorders

Catheter site pain¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

General disorders

Catheter site swelling¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

General disorders

Vessel puncture site bruise¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

General disorders

Vessel puncture site pain¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

Ear and labyrinth disorders

Tinnitus¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

Skin and subcutaneous tissue disorders

Dermatitis contact¹

# participants affected / at risk

0/30 (0.00%)

0/29 (0.00%)

0/14 (0.00%)

0/24 (0.00%)

1/24 (4.17%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 23.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: This confidential document is the property of AstraZeneca AB. No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca Clinical study Information Center
Phone	1-877-240-94 79
E-mail:	[email protected]

Documents available

Redacted CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Ronald Goldwater,

Parexel Early Phase Clinical Unit Baltimore

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Redacted CSR Synopsis

Trial Results Summaries