Study to Assess the Bioequivalence of Acalabrutinib Tablet and Acalabrutinib Capsule

Study identifier:D8223C00013

ClinicalTrials.gov identifier:NCT04768985

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, Open-Label, Randomized, 2-Treatment, 2-Period, Crossover Study in Healthy Subjects to Assess the Bioequivalence of Acalabrutinib Tablet and Acalabrutinib Capsule

Medical condition

bioequivalence

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Treatment A: Acalabrutinib tablet, Treatment B: Acalabrutinib capsule

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 25 Feb 2021

Primary Completion Date: 10 May 2021

Study Completion Date: 10 May 2021

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Crossover Assignment
Masking: -
Primary Purpose: Other

Verification:

Verified 01 Mar 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

• Females must have a negative pregnancy test at Screening and on admission to the study center, must not be lactating, and must be of non-childbearing potential, confirmed at Screening, by fulfilling protocol defined criteria
• Have a body mass index between 18.5 and 30 kg/m^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive, at Screening
• Non-smokers and those participants who have not smoked (including e cigarettes) or used nicotine products (cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or any other nicotine containing products) within the 90 days prior to Screening
• Calculated creatinine clearance (CrCl) ≥ 90 mL/min as determined by Cockcroft-Gault method (using actual body weight)
Males:
CrCl = Weight (kg) × (140 - Age)/72 × serum creatinine (mg/dL) in mL/min
Females:
CrCl = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL) in (mL/min)

Exclusion Criteria

• History or presence of any clinically significant disease (including active coronavirus disease 2019 [COVID-19] infection) or disorder
• History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• Any clinically significant illness, medical/surgical procedure, or trauma within 30 days of the first administration of study drug
• Any clinically significant abnormalities in hematology, coagulation, clinical chemistry, or urinalysis results, at Screening and prior to first dose, as judged by the Investigator and defined as:
(i) Hemoglobin less than lower limit of normal
(ii) Absolute neutrophils less than lower limit of normal
(iii) Platelets less than lower limit of normal
(iv) Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase or serum bilirubin (total bilirubin and direct bilirubin) > upper limit of normal
• Any clinically significant abnormal findings in vital signs at Screening or on Day 1 (eg, systolic BP < 90 mmHg or > 140 mmHg; diastolic BP < 50 mmHg or > 90 mmHg; pulse < 45 or > 90 bpm)
• Any clinically significant abnormalities on standard 12-lead ECG at Screening or on Day 1
• Any positive result for HBsAg, hepatitis C antibody, and HIV testing, at Screening
• Has received a new chemical entity (defined as a compound which has not been approved for marketing) within 90 days of the first administration of study drug in this study. The period of exclusion begins 90 days after the final dose or 30 days after the last visit whichever is the longest
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to acalabrutinib
• Positive screen for drugs of abuse or cotinine and alcohol, at Screening and on admission to the study center
• Treatment with prescription or non-prescription drugs or other products known to be strong CYP3A, P-gp, or breast cancer resistance protein (BCRP) inhibitors or substrates of BCRP or MATE1 (within 14 days before first administration of study drug or longer if the medication has a long half life) and strong CYP3A inducers (within 28 days before first administration of study drug or longer if the medication has a long half life)
• 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 14 days prior to the first administration of study drug or longer if the medication has a long half life
• Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by the Investigator
• Inability to swallow acalabrutinib tablets or acalabrutinib capsules
• Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections)
• Participant has a positive test result for severe acute respiratory syndrome coronavirus 2 reverse transcriptase polymerase chain reaction before randomization
• Participant has clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening or on admission
• History of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated)
• Participants who are regularly exposed to COVID-19 as part of their daily life (eg, health care professionals working in COVID-19 wards or at emergency departments)

Location

Research Site

Brooklyn, MD, United States, 21225

Location

Research Site

Glendale, CA, United States, 91206

Location

Research Site

Salt Lake City, UT, United States, 84107

Arms	Assigned Interventions
Experimental: Treatment sequence 1: Treatment AB Participants will be randomized to receive one of the two different treatment sequences. In each treatment sequence participant will receive fixed single doses of 100 mg acalabrutinib orally (Treatment A; Treatment B) in 2 treatment periods, under fasted conditions. Treatment A will include acalabrutinib tablet and Treatment B will include acalabrutinib capsule.	Drug: Treatment A: Acalabrutinib tablet Participants will receive fixed single doses of acalabrutinib tablet in 2 treatment periods, under fasted conditions. Other Name: CALQUENCE Drug: Treatment B: Acalabrutinib capsule Participants will receive fixed single doses of acalabrutinib capsule in 2 treatment periods, under fasted conditions. Other Name: CALQUENCE
Experimental: Treament sequence 2: Treatment BA Participants will be randomized to receive one of the two different treatment sequences. In each treatment sequence participant will receive fixed single doses of 100 mg acalabrutinib orally (Treatment B; Treatment A) in 2 treatment periods, under fasted conditions. Treatment A will include acalabrutinib tablet and Treatment B will include acalabrutinib capsule.	Drug: Treatment A: Acalabrutinib tablet Participants will receive fixed single doses of acalabrutinib tablet in 2 treatment periods, under fasted conditions. Other Name: CALQUENCE Drug: Treatment B: Acalabrutinib capsule Participants will receive fixed single doses of acalabrutinib capsule in 2 treatment periods, under fasted conditions. Other Name: CALQUENCE

Arms

Assigned Interventions

Experimental: Treatment sequence 1: Treatment AB
Participants will be randomized to receive one of the two different treatment sequences. In each treatment sequence participant will receive fixed single doses of 100 mg acalabrutinib orally (Treatment A; Treatment B) in 2 treatment periods, under fasted conditions. Treatment A will include acalabrutinib tablet and Treatment B will include acalabrutinib capsule.

Drug: Treatment A: Acalabrutinib tablet
Participants will receive fixed single doses of acalabrutinib tablet in 2 treatment periods, under fasted conditions.

Other Name: CALQUENCE

Drug: Treatment B: Acalabrutinib capsule
Participants will receive fixed single doses of acalabrutinib capsule in 2 treatment periods, under fasted conditions.

Other Name: CALQUENCE

Experimental: Treament sequence 2: Treatment BA
Participants will be randomized to receive one of the two different treatment sequences. In each treatment sequence participant will receive fixed single doses of 100 mg acalabrutinib orally (Treatment B; Treatment A) in 2 treatment periods, under fasted conditions. Treatment A will include acalabrutinib tablet and Treatment B will include acalabrutinib capsule.

Drug: Treatment A: Acalabrutinib tablet
Participants will receive fixed single doses of acalabrutinib tablet in 2 treatment periods, under fasted conditions.

Other Name: CALQUENCE

Drug: Treatment B: Acalabrutinib capsule
Participants will receive fixed single doses of acalabrutinib capsule in 2 treatment periods, under fasted conditions.

Other Name: CALQUENCE

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 between 25-February-2021 and 10-May-2021 in three sites in the United States (US).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.

Reporting Groups

	Description
Experimental: Treatment sequence 1: Treatment AB	Participants were randomized to receive one of the two different treatment sequences. In each treatment sequence, participant received fixed single doses of 100 mg acalabrutinib orally (Treatment A; Treatment B) in 2 treatment periods under fasted conditions. Treatment A included acalabrutinib tablet and Treatment B included acalabrutinib capsule.
Experimental: Treament sequence 2: Treatment BA	Participants were randomized to receive one of the two different treatment sequences. In each treatment sequence, participant received fixed single doses of 100 mg acalabrutinib orally (Treatment B; Treatment A) in 2 treatment periods under fasted conditions. Treatment A included acalabrutinib tablet and Treatment B included acalabrutinib capsule.

Participant Flow: Overall Study

	Experimental: Treatment sequence 1: Treatment AB	Experimental: Treament sequence 2: Treatment BA
STARTED	35	31
COMPLETED	34	30
NOT COMPLETED	1	1
Withdrawal by Subject	0	1
Lost to Follow-up	1	0

Baseline Characteristics

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

The Randomized Set included all participants randomized into the study.

Reporting Groups

	Description
Experimental: Treatment sequence 1: Treatment AB	Participants were randomized to receive one of the two different treatment sequences. In each treatment sequence, participant received fixed single doses of 100 mg acalabrutinib orally (Treatment A; Treatment B) in 2 treatment periods under fasted conditions. Treatment A included acalabrutinib tablet and Treatment B included acalabrutinib capsule.
Experimental: Treament sequence 2: Treatment BA	Participants were randomized to receive one of the two different treatment sequences. In each treatment sequence, participant received fixed single doses of 100 mg acalabrutinib orally (Treatment B; Treatment A) in 2 treatment periods under fasted conditions. Treatment A included acalabrutinib tablet and Treatment B included acalabrutinib capsule.

Baseline Measures

	Experimental: Treatment sequence 1: Treatment AB	Experimental: Treament sequence 2: Treatment BA	Total
Number of Participants [units: Participants]	35	31	66
Age Continuous [units: years] Mean ± Standard Deviation	35.9 ± 10.4	36.6 ± 10.7	36.2 ± 10.4
Sex: Female, Male [units: Participants]
Female	2	2	4
Male	33	29	62
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0
Asian	2	1	3
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	16	13	29
White	16	17	33
More than one race	0	0	0
Unknown or Not Reported	1	0	1
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	5	9	14
Not Hispanic or Latino	30	22	52
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: Area under plasma concentration-time curve from zero to infinity (AUCinf) of acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Primary
Measure Name	Area under plasma concentration-time curve from zero to infinity (AUCinf) of acalabrutinib
Measure Description	Comparison of AUCinf for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for Acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or adverse events (AEs) considered to impact the analysis of the pharmacokinetic (PK) data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Area under plasma concentration-time curve from zero to infinity (AUCinf) of acalabrutinib [units: h·ng/mL] Geometric Mean (Geometric Coefficient of Variation)	567.8 (36.90%)	572.2 (38.16%)

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

Groups^[1]	All groups
Method^[3]	ANOVA
Other^[5]	98.56
90% Confidence Interval	( 93.44 to 103.96 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise Comparison (A/B)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimation method with estimation parameter as geometric mean ratio and confidence intervals from linear mixed effect analysis of variance (ANOVA).
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Area under plasma concentration-time curve from zero to the last quantifiable concentration (AUClast) of acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Primary
Measure Name	Area under plasma concentration-time curve from zero to the last quantifiable concentration (AUClast) of acalabrutinib
Measure Description	Comparison of AUClast for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for Acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Area under plasma concentration-time curve from zero to the last quantifiable concentration (AUClast) of acalabrutinib [units: h·ng/mL] Geometric Mean (Geometric Coefficient of Variation)	563.9 (36.89%)	566.8 (38.60%)

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

Groups^[1]	All groups
Method^[3]	ANOVA
Other^[5]	98.78
90% Confidence Interval	( 93.61 to 104.24 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise Comparison (A/B)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimation method with estimation parameter as geometric mean ratio and confidence intervals from linear mixed effect analysis of variance (ANOVA).
[5]	Other relevant estimation information:
	No text entered.

3. Primary Outcome Measure: Maximum observed plasma (peak) drug concentration (Cmax) of acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Primary
Measure Name	Maximum observed plasma (peak) drug concentration (Cmax) of acalabrutinib
Measure Description	Comparison of Cmax for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for Acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Maximum observed plasma (peak) drug concentration (Cmax) of acalabrutinib [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	537.2 (42.61%)	535.7 (58.43%)

Statistical Analysis 1 for Maximum observed plasma (peak) drug concentration (Cmax) of acalabrutinib

Groups^[1]	All groups
Method^[3]	ANOVA
Other^[5]	100.36
90% Confidence Interval	( 90.78 to 110.96 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise Comparison (A/B)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimation method with estimation parameter as geometric mean ratio and confidence intervals from linear mixed effect analysis of variance (ANOVA).
[5]	Other relevant estimation information:
	No text entered.

4. Primary Outcome Measure: Time to reach peak or maximum concentration (tmax) following drug administration for acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Primary
Measure Name	Time to reach peak or maximum concentration (tmax) following drug administration for acalabrutinib
Measure Description	Comparison of tmax for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for Acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Time to reach peak or maximum concentration (tmax) following drug administration for acalabrutinib [units: hour (h)] Median (Full Range)	0.52 (0.23 to 2.97)	0.58 (0.47 to 3.98)

No statistical analysis provided for Time to reach peak or maximum concentration (tmax) following drug administration for acalabrutinib

5. Primary Outcome Measure: Half‑life associated with terminal slope (λz) of a semi‑logarithmic concentration‑time curve (t1/2λz) for acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Primary
Measure Name	Half‑life associated with terminal slope (λz) of a semi‑logarithmic concentration‑time curve (t1/2λz) for acalabrutinib
Measure Description	Comparison of t1/2λz for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for Acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Half‑life associated with terminal slope (λz) of a semi‑logarithmic concentration‑time curve (t1/2λz) for acalabrutinib [units: hour (h)] Mean (Standard Deviation)	1.643 (1.179)	2.237 (2.823)

No statistical analysis provided for Half‑life associated with terminal slope (λz) of a semi‑logarithmic concentration‑time curve (t1/2λz) for acalabrutinib

6. Primary Outcome Measure: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Primary
Measure Name	Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for acalabrutinib
Measure Description	Comparison of MRT for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for Acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for acalabrutinib [units: hour (h)] Mean (Standard Deviation)	1.526 (0.4818)	1.852 (1.156)

No statistical analysis provided for Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for acalabrutinib

7. Primary Outcome Measure: Terminal rate constant estimated by log linear least squares regression of terminal part of concentration time curve (λz) for acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Primary
Measure Name	Terminal rate constant estimated by log linear least squares regression of terminal part of concentration time curve (λz) for acalabrutinib
Measure Description	Comparison of λz for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for Acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Terminal rate constant estimated by log linear least squares regression of terminal part of concentration time curve (λz) for acalabrutinib [units: 1/hour] Mean (Standard Deviation)	0.5295 (0.2032)	0.4844 (0.2404)

No statistical analysis provided for Terminal rate constant estimated by log linear least squares regression of terminal part of concentration time curve (λz) for acalabrutinib

8. Secondary Outcome Measure: Area under plasma concentration-time curve from zero to infinity (AUCinf) of ACP-5862 [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve from zero to infinity (AUCinf) of ACP-5862
Measure Description	Comparison of AUCinf for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	63	63
Area under plasma concentration-time curve from zero to infinity (AUCinf) of ACP-5862 [units: h·ng/mL] Geometric Mean (Geometric Coefficient of Variation)	1488 (28.56%)	1460 (30.03%)

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

Groups^[1]	All groups
Method^[3]	ANOVA
Other^[5]	101.54
90% Confidence Interval	( 98.23 to 104.96 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise Comparison (A/B)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimation method with estimation parameter as geometric mean ratio and confidence intervals from linear mixed effect analysis of variance (ANOVA).
[5]	Other relevant estimation information:
	No text entered.

9. Secondary Outcome Measure: Area under the plasma concentration-time curve from zero to the last quantifiable concentration (AUClast) of ACP-5862 [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve from zero to the last quantifiable concentration (AUClast) of ACP-5862
Measure Description	Comparison of AUClast for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Area under the plasma concentration-time curve from zero to the last quantifiable concentration (AUClast) of ACP-5862 [units: h·ng/mL] Geometric Mean (Geometric Coefficient of Variation)	1396 (29.44%)	1374 (31.63%)

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

Groups^[1]	All groups
Method^[3]	ANOVA
Other^[5]	101.76
90% Confidence Interval	( 98.16 to 105.48 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise Comparison (A/B)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimation method with estimation parameter as geometric mean ratio and confidence intervals from linear mixed effect analysis of variance (ANOVA).
[5]	Other relevant estimation information:
	No text entered.

10. Secondary Outcome Measure: Maximum observed plasma (peak) drug concentration (Cmax) of ACP-5862 [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Maximum observed plasma (peak) drug concentration (Cmax) of ACP-5862
Measure Description	Comparison of Cmax for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Maximum observed plasma (peak) drug concentration (Cmax) of ACP-5862 [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)	476.6 (29.80%)	459.9 (45.10%)

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

Groups^[1]	All groups
Method^[3]	ANOVA
Other^[5]	103.68
90% Confidence Interval	( 95.70 to 112.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Pairwise Comparison (A/B)
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Estimation method with estimation parameter as geometric mean ratio and confidence intervals from linear mixed effect analysis of variance (ANOVA).
[5]	Other relevant estimation information:
	No text entered.

11. Secondary Outcome Measure: Time to reach peak or maximum concentration (tmax) following drug administration for ACP-5862 [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Time to reach peak or maximum concentration (tmax) following drug administration for ACP-5862
Measure Description	Comparison of tmax for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Time to reach peak or maximum concentration (tmax) following drug administration for ACP-5862 [units: hour (h)] Median (Full Range)	0.75 (0.48 to 3.98)	0.95 (0.47 to 3.98)

No statistical analysis provided for Time to reach peak or maximum concentration (tmax) following drug administration for ACP-5862

12. Secondary Outcome Measure: Half‑life associated with terminal slope (λz) of a semi‑logarithmic concentration‑time curve (t1/2λz) for ACP-5862 [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Half‑life associated with terminal slope (λz) of a semi‑logarithmic concentration‑time curve (t1/2λz) for ACP-5862
Measure Description	Comparison of t1/2λz for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	63	63
Half‑life associated with terminal slope (λz) of a semi‑logarithmic concentration‑time curve (t1/2λz) for ACP-5862 [units: hour (h)] Mean (Standard Deviation)	6.890 (1.732)	6.970 (1.870)

No statistical analysis provided for Half‑life associated with terminal slope (λz) of a semi‑logarithmic concentration‑time curve (t1/2λz) for ACP-5862

13. Secondary Outcome Measure: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for ACP-5862 [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for ACP-5862
Measure Description	Comparison of MRT for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	63	63
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for ACP-5862 [units: hour (h)] Mean (Standard Deviation)	6.018 (1.092)	6.391 (1.643)

No statistical analysis provided for Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for ACP-5862

14. Secondary Outcome Measure: Terminal rate constant estimated by log linear least squares regression of terminal part of concentration time curve (λz) for ACP-5862 [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Terminal rate constant estimated by log linear least squares regression of terminal part of concentration time curve (λz) for ACP-5862
Measure Description	Comparison of λz for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Terminal rate constant estimated by log linear least squares regression of terminal part of concentration time curve (λz) for ACP-5862 [units: 1/hour] Mean (Standard Deviation)	0.1106 (0.04289)	0.1096 (0.04112)

No statistical analysis provided for Terminal rate constant estimated by log linear least squares regression of terminal part of concentration time curve (λz) for ACP-5862

15. Secondary Outcome Measure: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for acalabrutinib
Measure Description	Comparison of CL/F for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) for acalabrutinib [units: Litre per hour (L/h)] Mean (Standard Deviation)	188.1 (76.46)	187.2 (73.61)

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

16. Secondary Outcome Measure: Volume of distribution (apparent) at steady state following extravascular administration [based on terminal phase] (Vz/F) for acalabrutinib [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Volume of distribution (apparent) at steady state following extravascular administration [based on terminal phase] (Vz/F) for acalabrutinib
Measure Description	Comparison of Vz/F for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for acalabrutinib.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Volume of distribution (apparent) at steady state following extravascular administration [based on terminal phase] (Vz/F) for acalabrutinib [units: Litre (L)] Mean (Standard Deviation)	408.2 (235.9)	605.4 (933.0)

No statistical analysis provided for Volume of distribution (apparent) at steady state following extravascular administration [based on terminal phase] (Vz/F) for acalabrutinib

17. Secondary Outcome Measure: Metabolite (ACP-5862) to parent (acalabrutinib) ratio based on AUCinf and/or AUClast (M:P[AUC]) [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Metabolite (ACP-5862) to parent (acalabrutinib) ratio based on AUCinf and/or AUClast (M:P[AUC])
Measure Description	Comparison of M:P[AUC] for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data. Here, overall number of participants analyzed signifies only the participants with available data for the outcome measure.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	63	63
Metabolite (ACP-5862) to parent (acalabrutinib) ratio based on AUCinf and/or AUClast (M:P[AUC]) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	2.554 (26.60%)	2.467 (30.55%)

No statistical analysis provided for Metabolite (ACP-5862) to parent (acalabrutinib) ratio based on AUCinf and/or AUClast (M:P[AUC])

18. Secondary Outcome Measure: Metabolite (ACP-5862) to parent [acalabrutinib] ratio based on Cmax (M:P [Cmax]) [ Time Frame: Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose). ]

Measure Type	Secondary
Measure Name	Metabolite (ACP-5862) to parent [acalabrutinib] ratio based on Cmax (M:P [Cmax])
Measure Description	Comparison of M:P [Cmax] for treatment A (Acalabrutinib Maleate Tablet, 100 mg, fasted state) vs. treatment B (Acalabrutinib capsule, 100 mg, fasted state) for ACP-5862.
Time Frame	Day 1 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 h post-dose); Day 2 (24 h post-dose), Day 3 (48 h post-dose).
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 Pharmacokinetic Analysis Set included all participants in the safety analysis set who had at least 1 quantifiable post-dose acalabrutinib concentration with no important protocol deviations or AEs considered to impact the analysis of the PK data.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Metabolite (ACP-5862) to parent [acalabrutinib] ratio based on Cmax (M:P [Cmax]) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	0.8577 (32.34%)	0.8301 (42.95%)

No statistical analysis provided for Metabolite (ACP-5862) to parent [acalabrutinib] ratio based on Cmax (M:P [Cmax])

19. Secondary Outcome Measure: Number of participants with adverse events and serious adverse events [ Time Frame: From screening day (Day -28) until Follow-up/end of treatment visit (at 7 to 10 days after last study drug administration). ]

Measure Type	Secondary
Measure Name	Number of participants with adverse events and serious adverse events
Measure Description	Comparison of the safety and tolerability of single doses of AMT and acalabrutinib capsule.
Time Frame	From screening day (Day -28) until Follow-up/end of treatment visit (at 7 to 10 days after last study drug administration).
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.
The Safety Analysis Set included all participants who received at least 1 dose of drug in Treatment Period 1 and for whom any post dose safety data were available.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received fixed single doses of AMT in 2 treatment periods under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received fixed single doses of acalabrutinib capsule in 2 treatment periods under fasted conditions.

Measured Values

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Number of Participants Analyzed [units:participants]	65	63
Number of participants with adverse events and serious adverse events [units: Participants]
Any AE	10	3
Any AE with outcome = death	0	0
Any SAE (including events with outcome = death)	0	0
Any AE leading to discontinuation of Investigational Medicinal Product (IMP)	0	0
Any AE leading to dose interruption	0	0
Any AE leading to dose reduction	0	0
Any AE leading to withdrawal from study	0	0

No statistical analysis provided for Number of participants with adverse events and serious adverse events

Serious Adverse Events

Time Frame	From screening day (Day 28) until follow-up/end of treatment visit (7 to 10 days after last study drug administration)
Additional Description	No text entered.

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received a fixed single dose of 100 mg AMT under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received a fixed single dose of 100 mg acalabrutinib capsule under fasted conditions.

Serious Adverse Events

	Treatment A: AMT, 100 mg, fasted state	Treament B: Acalabrutinib capsule, 100mg, fasted state
Total, serious adverse events
# participants affected / at risk	0/65 (0.00%)	0/63 (0.00%)

Other Adverse Events

Time Frame	From screening day (Day 28) until follow-up/end of treatment visit (7 to 10 days after last study drug administration)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Treatment A: AMT, 100 mg, fasted state	Participants received a fixed single dose of 100 mg AMT under fasted conditions.
Treament B: Acalabrutinib capsule, 100mg, fasted state	Participants received a fixed single dose of 100 mg acalabrutinib capsule under fasted conditions.