Study of Acalabrutinib in Chinese Adult Subjects With Rel... | NCT03932331

ID	Type	Description	Link
2018L02939	Registry Identifier	CFDA/ NMPA

Label	Type	Description	Intervention Names
Acalabrutinib	Experimental	Acalabrutinib will be orally administered until disease progression or unacceptable toxicity.	Drug: Acalabrutinib

Name	Type	Description	Arm Group Labels	Other Names
Acalabrutinib	Drug	Acalabrutinib 100 mg orally twice daily	Acalabrutinib

Measure	Description	Time Frame
Phase I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A SAE is an AE occurring during any study phase, that fulfils 1 or more of the following criteria: death, life-threatening, in-participant hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital abnormality or birth defect, and an important medical event that may jeopardize the participant or may require medical treatment to prevent 1 of the outcomes listed above. AEs leading to discontinuation of acalabrutinib were those with action taken was 'Drug Permanently Discontinued' for acalabrutinib.	From the first dose administration up to 30 days following the date of last dose of study treatment, approximately 25 months.
Phase I: Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUCinf) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib	Blood samples were collected to determine the AUCinf of acalabrutinib and ACP-5862 in plasma. The AUCinf was determined using non-compartmental method.	Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1
Phase I: Area Under the Plasma Concentration-Time Curve From Zero to 12 Hours (AUC0-12) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib	Blood samples were collected to determine the AUC0-12 of acalabrutinib and ACP-5862 in plasma. The AUC0-12 was determined using non-compartmental method.	Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 12 hours postdose on Cycle 0 Day 1
Phase I: Area Under the Plasma Concentration-Time Curve From Zero to the Time of the Last Quantifiable Concentration (AUClast) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib	Blood samples were collected to determine the AUClast of acalabrutinib and ACP-5862 in plasma. The AUClast was determined using non-compartmental method.

Measure	Description	Time Frame
Phase I: Best Overall Response (BOR) Assessed by Investigator in Participants With R/R CLL	The BOR is best response a participant has had following first dose date but prior to starting any subsequent anticancer therapy up to and including progression or last evaluable assessment in absence of progression. The CR: No lymph nodes >=1.5 centimeters. The CRi: Participants who fulfill all criteria for CR but have a persistent anemia, thrombocytopenia or neutropenia apparently unrelated to CLL but related to drug toxicity. The nPR: Participants who were in a complete remission but bone marrow nodules can be identified histologically. The PR: Disease >=50% from baseline. Partial response with lymphocytosis (PRL): Presence of lymphocytosis plus >=50% reduction in lymphadenopathy and/or in spleen or liver enlargement plus 1 of PR criteria for platelets or hemoglobin must be met. Stable disease (SD): Change of -49% to +49% in lymph nodes. PD: Increase >=50% from baseline or from response.

Name	Affiliation	Role
Jun Zhu, Prof	Peking University Cancer Hospital & Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Beijing		100044	China
Research Site

PubMed Identifier	Type	Citation	Retractions
39271521	Derived	Yang S, Huang H, Zhou K, Zhao X, Han Y, Li L, Wang Y, Liu X, Li J. Acalabrutinib in Chinese patients with relapsed/refractory chronic lymphocytic leukemia: Primary analysis from an open-label, multicenter phase 1/2 trial. Ann Hematol. 2025 Jan;104(1):701-712. doi: 10.1007/s00277-024-05978-4. Epub 2024 Sep 14.
38557285	Derived

Label	URL
Related Info	View source

ID	Title	Description
FG000	Phase I	Participants received single dose of acalabrutinib 100 milligram (mg) capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 7, 2023	Aug 25, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase I: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A SAE is an AE occurring during any study phase, that fulfils 1 or more of the following criteria: death, life-threatening, in-participant hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital abnormality or birth defect, and an important medical event that may jeopardize the participant or may require medical treatment to prevent 1 of the outcomes listed above. AEs leading to discontinuation of acalabrutinib were those with action taken was 'Drug Permanently Discontinued' for acalabrutinib.

The Safety analysis set included all participants who received at least 1 dose of acalabrutinib.

Posted

Count of Participants

Participants

From the first dose administration up to 30 days following the date of last dose of study treatment, approximately 25 months.

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG00012

Title

Denominators

Categories

Any AE

Title	Measurements
	OG00012

Any SAE

Title	Measurements
	OG0002

Any AE leading to discontinuation of Acalabrutinib

Primary

Phase I: Area Under the Plasma Concentration-Time Curve From Zero to Infinity (AUCinf) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

Blood samples were collected to determine the AUCinf of acalabrutinib and ACP-5862 in plasma. The AUCinf was determined using non-compartmental method.

The Pharmacokinetics (PK) analysis set included all participants who received at least 1 dose of acalabrutinib with reportable acalabrutinib plasma concentration and PK parameter data with no important protocol deviations that may impact PK.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour*nanogram per milliliter (h*ng/mL)

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Area Under the Plasma Concentration-Time Curve From Zero to 12 Hours (AUC0-12) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

Blood samples were collected to determine the AUC0-12 of acalabrutinib and ACP-5862 in plasma. The AUC0-12 was determined using non-compartmental method.

The PK analysis set included all participants who received at least 1 dose of acalabrutinib with reportable acalabrutinib plasma concentration and PK parameter data with no important protocol deviations that may impact PK.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 12 hours postdose on Cycle 0 Day 1

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Area Under the Plasma Concentration-Time Curve From Zero to the Time of the Last Quantifiable Concentration (AUClast) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

Blood samples were collected to determine the AUClast of acalabrutinib and ACP-5862 in plasma. The AUClast was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Maximum Observed Plasma Drug Concentration (Cmax) of Acalabrutinib and ACP-5862 Post Single and Multiple Dose of Acalabrutinib

Blood samples were collected to determine the Cmax of acalabrutinib and ACP-5862 in plasma. The Cmax was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Single dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 12 hours postdose on Cycle 0 Day 1; Multiple dose: Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Time to Reach Maximum Observed Concentration (Tmax) of Acalabrutinib and ACP-5862 Post Single and Multiple Dose of Acalabrutinib

Blood samples were collected to determine the tmax of acalabrutinib and ACP-5862 in plasma. The tmax was determined using non-compartmental method.

Posted

Median

Full Range

hour

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Apparent Total Body Clearance of Drug (CL/F) of Acalabrutinib Post Single and Multiple Dose of Acalabrutinib

Urine samples were collected to determine the CL/F of acalabrutinib. The CL/F was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

liter per hour

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Apparent Volume of Distribution (Vz/F) of Acalabrutinib Post Single Dose of Acalabrutinib

Blood samples were collected to determine the Vz/F of acalabrutinib in plasma. The Vz/F was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

liter

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Terminal Elimination Rate Constant (λz) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

Blood samples were collected to determine the λz of acalabrutinib and ACP-5862 in plasma. The λz was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

1/hour

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Terminal Phase Half-Life (t1/2λz) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

Blood samples were collected to determine the t1/2λz of acalabrutinib and ACP-5862 in plasma. The t1/2λz was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Metabolite/Parent Drug Cmax Ratio (MRCmax) of Acalabrutinib and ACP-5862 Post Single and Multiple Dose of Acalabrutinib

Blood samples were collected to determine the MRCmax of acalabrutinib and ACP-5862 in plasma. The MRCmax was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Metabolite/Parent Drug AUC Ratio (MRAUCinf) of Acalabrutinib and ACP-5862 Post Single Dose of Acalabrutinib

Blood samples were collected to determine the MRAUCinf of acalabrutinib in plasma. The MRAUCinf was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 0 Day 1

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Area Under the Plasma Concentration-Time Curve Across the Dosing Interval (AUCτ) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

Blood samples were collected to determine the AUCτ of acalabrutinib and ACP-5862 in plasma. The AUCτ was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Minimum Observed Plasma Drug Concentration (Cmin) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

Blood samples were collected to determine the Cmin of acalabrutinib and ACP-5862 in plasma. The Cmin was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Metabolite/Parent Drug AUCτ Ratio (MRAUCτ) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

Blood samples were collected to determine the MRAUCτ of acalabrutinib and ACP-5862 in plasma. The MRAUCτ was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Temporal Change Parameter (TCP) in Systemic Exposure of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

Blood samples were collected to determine the TCP of acalabrutinib and ACP-5862 in plasma. The TCP in systemic exposure was calculated as AUCτ (steady state)/AUCinf (first dose). The TCP was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Accumulation Ratio of AUCτ (Rac AUC) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

Blood samples were collected to determine the Rac AUC of acalabrutinib and ACP-5862 in plasma. The Rac AUC was calculated as AUCτ (steady state)/AUCτ (first dose). The Rac AUC was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase I: Accumulation Ratio of Cmax (Rac Cmax) of Acalabrutinib and ACP-5862 Post Multiple Dose of Acalabrutinib

Blood samples were collected to determine the Rac Cmax of acalabrutinib and ACP-5862 in plasma. The Rac Cmax was calculated as Cmax (steady state)/Cmax (first dose). The Rac Cmax was determined using non-compartmental method.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

Pre-dose and 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24 and 48 hours postdose on Cycle 1 Day 8

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Primary

Phase II: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR)

The ORR [based on International workshop on chronic lymphocytic leukemia (iwCLL) 2018 criteria as assessed by the BICR] was defined as the percentage of participants who achieved a complete response (CR), CR with incomplete marrow recovery (CRi), nodular partial response (nPR), and partial response (PR). The ORR and the corresponding 95% 2-sided confidence interval (CI) of ORR were presented based on Clopper-Pearson exact method.

Tumour response analysis set included all participants who received at least 1 dose of acalabrutinib with an available baseline tumour assessment. One participant from Phase I rolled over to Phase II MCL reporting group.

Posted

Number

95% Confidence Interval

percentage of participants

Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

ID	Title	Description
OG000	Phase II MCL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
OG001	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Secondary

Phase I: Best Overall Response (BOR) Assessed by Investigator in Participants With R/R CLL

The BOR is best response a participant has had following first dose date but prior to starting any subsequent anticancer therapy up to and including progression or last evaluable assessment in absence of progression. The CR: No lymph nodes >=1.5 centimeters. The CRi: Participants who fulfill all criteria for CR but have a persistent anemia, thrombocytopenia or neutropenia apparently unrelated to CLL but related to drug toxicity. The nPR: Participants who were in a complete remission but bone marrow nodules can be identified histologically. The PR: Disease >=50% from baseline. Partial response with lymphocytosis (PRL): Presence of lymphocytosis plus >=50% reduction in lymphadenopathy and/or in spleen or liver enlargement plus 1 of PR criteria for platelets or hemoglobin must be met. Stable disease (SD): Change of -49% to +49% in lymph nodes. PD: Increase >=50% from baseline or from response.

Tumour response analysis set included all participants who received at least 1 dose of acalabrutinib with an available baseline tumour assessment. Only participants with R/R CLL are analyzed in this outcome measure.

Posted

Count of Participants

Participants

Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days thereafter or more frequently at the investigator's discretion, approximately 25 months

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Secondary

Phase I: Best Overall Response Assessed by Investigator in Participants With R/R MCL

The BOR is best response a participant has had following first dose date but prior to starting any subsequent anticancer therapy up to and including progression or last evaluable assessment in absence of progression. CR: No lymph nodes >=1.5 centimeters. PR: Disease >=50% from baseline. SD: Change of -49% to +49% in lymph nodes. PD: Increase >=50% from baseline or from response.

Tumour response analysis set included all participants who received at least 1 dose of acalabrutinib with an available baseline tumour assessment. Only participants with R/R MCL are analyzed in this outcome measure.

Posted

Count of Participants

Participants

Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days thereafter or more frequently at the investigator's discretion, approximately 25 months

ID	Title	Description
OG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants

Secondary

Phase II: ORR Assessed by Investigator

The ORR (based on iwCLL 2018 criteria as assessed by the Investigator) was defined as the percentage of participants who achieved a CR, CRi, nPR, and PR. The ORR and the corresponding 95% 2-sided CI of ORR were presented based on Clopper-Pearson exact method.

Posted

Number

95% Confidence Interval

percentage of participants

Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

ID	Title	Description
OG000	Phase II MCL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
OG001	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts

Secondary

Phase II: Duration of Response (DoR) Assessed by BICR and Investigator

The DoR (based on iwCLL 2018 criteria as assessed by the BICR and Investigator) was defined as the interval from the first documentation of objective response to the earlier of the first documentation of objective PD or death from any cause. The DoR was calculated using Kaplan-Meier technique.

Tumour response analysis set included all participants who received at least 1 dose of acalabrutinib with an available baseline tumour assessment. Only participants who achieved PR or above were analyzed.

Posted

Median

Inter-Quartile Range

months

Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

ID	Title	Description
OG000	Phase II MCL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
OG001	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units

Secondary

Phase II: Progression-Free Survival (PFS) Assessed by BICR and Investigator

The PFS (based on iwCLL 2018 criteria as assessed by the BICR and Investigator) was defined as the interval from the start of acalabrutinib therapy to the earlier of the first documentation of objective PD or death from any cause. The PFS was calculated using Kaplan-Meier technique.

Posted

Median

95% Confidence Interval

months

Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

ID	Title	Description
OG000	Phase II MCL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
OG001	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units

Secondary

Phase II: Time to Response (TTR) Assessed by BICR and Investigator

The TTR (based on iwCLL 2018 criteria as assessed by the BICR and Investigator) was defined as the interval between the date of first dose and the date of initial documentation of a response.

Tumour response analysis set included all participants who received at least 1 dose of acalabrutinib with an available baseline tumour assessment. Only participants with response were analyzed.

Posted

Median

Full Range

months

Response evaluations performed at the end of Cycles 2, 4 and 6; and then every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

ID	Title	Description
OG000	Phase II MCL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
OG001	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants

Secondary

Phase II CLL Only: Time to Next Treatment (TTNT)

The TTNT was defined as the interval from the start of acalabrutinib therapy to institution of non-protocol specified anticancer treatment for CLL or death due to any cause, whichever came first. The TTNT was calculated using Kaplan-Meier technique.

Tumour response analysis set included all participants who received at least 1 dose of acalabrutinib with an available baseline tumour assessment.

Posted

Median

95% Confidence Interval

months

Response evaluations performed every 12 weeks +/- 7 days through Cycle 25, and then every 24 weeks +/- 7 days thereafter. Assessed until 18 December 2023.

ID	Title	Description
OG000	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Secondary

Phase II CLL Only: Percentage of Participants With Minimal Residual Disease (MRD) Negativity

The MRD negative rate was defined as the percentage of participants with MRD-negativity (<1 CLL cell per 10000 leukocytes) measured in the peripheral blood by flow cytometry.

Tumour response analysis set included all participants who received at least 1 dose of acalabrutinib with an available baseline tumour assessment.

Posted

Number

percentage of participants

At screening (-28 days) and end of treatment visit. Assessed until 18 December 2023.

ID	Title	Description
OG000	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Secondary

Phase II: Percentage of Participants With Overall Survival (OS) at Month 6

The OS was defined as the interval from the start of acalabrutinib therapy to death from any cause. The OS was calculated using Kaplan-Meier technique.

Posted

Number

95% Confidence Interval

percentage of participants

From the first dose administration up to Month 6

ID	Title	Description
OG000	Phase II MCL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
OG001	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants

Secondary

Phase II: Plasma Concentration of Acalabrutinib

Blood samples were collected to determine the plasma concentration of acalabrutinib.

The pharmacokinetics (PK) analysis set included all participants who received at least 1 dose of acalabrutinib with reportable acalabrutinib plasma concentration and PK parameter data with no important protocol deviations that may impact PK.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter

At 1, 2 and 4 hours post-dose on Day 8, 15 and 22 of Cycle 1

ID	Title	Description
OG000	Phase II MCL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
OG001	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected12 at risk EG0016 events3 affected34 at risk EG0028 events6 affected60 at risk
Mastoiditis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Nasal herpes	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events2 affected60 at risk
Pelvic inflammatory disease	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Periodontitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Pharyngitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Pneumonia	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0013 events3 affected34 at risk EG00217 events12 affected60 at risk
Pneumonia fungal	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Pneumonia viral	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Rash pustular	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Angina pectoris	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Skin infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Suspected covid-19	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0006 events3 affected12 at risk EG0019 events8 affected34 at risk EG00215 events11 affected60 at risk
Urethritis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected12 at risk EG0012 events1 affected34 at risk EG0029 events8 affected60 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0021 events1 affected60 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Arrhythmia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0020 events0 affected60 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected12 at risk EG00111 events6 affected34 at risk EG00210 events8 affected60 at risk
Alpha hydroxybutyrate dehydrogenase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0019 events7 affected34 at risk EG0028 events8 affected60 at risk
Band neutrophil count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Basophil count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events2 affected60 at risk
Beta 2 microglobulin increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Bilirubin conjugated increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0022 events2 affected60 at risk
Blood albumin decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events3 affected34 at risk EG0023 events2 affected60 at risk
Blood bicarbonate increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood bilirubin increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG00114 events6 affected34 at risk EG0025 events5 affected60 at risk
Blood cholesterol increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0025 events3 affected60 at risk
Blood creatinine increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0024 events4 affected60 at risk
Blood fibrinogen decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood fibrinogen increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events1 affected60 at risk
Blood glucose increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Blood immunoglobulin a decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Blood immunoglobulin g decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Blood immunoglobulin g increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events1 affected60 at risk
Blood immunoglobulin m decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0022 events2 affected60 at risk
Blood immunoglobulin m increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected34 at risk EG0029 events5 affected60 at risk
Blood magnesium increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood phosphorus decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events1 affected60 at risk
Blood phosphorus increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood potassium decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood sodium increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood triglycerides increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events1 affected34 at risk EG0024 events3 affected60 at risk
Blood urea increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Bundle branch block right	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Blood uric acid increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0027 events5 affected60 at risk
Blood urine present	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0022 events1 affected60 at risk
C-reactive protein increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Cd19 lymphocytes decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Cd19 lymphocytes increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Cd4 lymphocytes increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Cd8 lymphocytes increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Cell marker decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Complement factor c3 decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events1 affected60 at risk
Complement factor c4 increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Electrocardiogram p wave abnormal	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Electrocardiogram pr shortened	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Electrocardiogram q waves	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Electrocardiogram qrs complex abnormal	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Electrocardiogram qt prolonged	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Electrocardiogram st segment abnormal	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Electrocardiogram st segment depression	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0026 events2 affected60 at risk
Electrocardiogram st-t change	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events1 affected60 at risk
Electrocardiogram st-t segment abnormal	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Electrocardiogram t wave abnormal	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Cardiac failure	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Electrocardiogram high voltage	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Eosinophil count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0023 events3 affected60 at risk
Globulins decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0029 events4 affected60 at risk
Glucose urine present	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Haematocrit decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG00210 events9 affected60 at risk
Haemoglobin decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG00220 events14 affected60 at risk
Helicobacter test positive	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Hepatitis b dna increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Hepatitis b core antibody positive	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Conduction disorder	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
High density lipoprotein decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
High density lipoprotein increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0024 events2 affected60 at risk
International normalised ratio increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Lipoprotein increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Low density lipoprotein increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0025 events2 affected60 at risk
Lymphocyte count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0004 events2 affected12 at risk EG0012 events1 affected34 at risk EG0020 events0 affected60 at risk
Lymphocyte count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0019 events8 affected34 at risk EG00212 events6 affected60 at risk
Lymphocyte percentage increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0022 events2 affected60 at risk
Monocyte count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Monocyte count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0024 events2 affected60 at risk
Natural killer cell count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Neutrophil count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0008 events4 affected12 at risk EG00110 events7 affected34 at risk EG00248 events28 affected60 at risk
Neutrophil count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0025 events3 affected60 at risk
Non-high-density lipoprotein cholesterol increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Platelet count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0007 events4 affected12 at risk EG00119 events14 affected34 at risk EG00233 events24 affected60 at risk
Protein total decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0029 events4 affected60 at risk
Protein urine present	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Prothrombin level increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Prothrombin time prolonged	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Qrs axis abnormal	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG00011 events4 affected12 at risk EG0018 events8 affected34 at risk EG00220 events14 affected60 at risk
Defect conduction intraventricular	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Red blood cell count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG00210 events8 affected60 at risk
Red blood cells urine positive	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events1 affected34 at risk EG0024 events2 affected60 at risk
Sars-cov-2 test positive	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
T-lymphocyte count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Urinary occult blood positive	Investigations	MedDRA 26.1	Systematic Assessment	EG0004 events2 affected12 at risk EG0011 events1 affected34 at risk EG0024 events4 affected60 at risk
Weight decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Weight increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
White blood cell count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0007 events5 affected12 at risk EG0013 events3 affected34 at risk EG0027 events3 affected60 at risk
White blood cell count increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0025 events4 affected60 at risk
White blood cells urine positive	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0024 events3 affected60 at risk
Palpitations	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0021 events1 affected60 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events1 affected34 at risk EG0021 events1 affected60 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected34 at risk EG0025 events4 affected60 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0013 events2 affected34 at risk EG0027 events3 affected60 at risk
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0026 events2 affected60 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0015 events4 affected34 at risk EG0023 events2 affected60 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0006 events4 affected12 at risk EG00111 events5 affected34 at risk EG00216 events8 affected60 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events2 affected34 at risk EG0020 events0 affected60 at risk
Pericardial effusion	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0005 events2 affected12 at risk EG0015 events5 affected34 at risk EG0028 events4 affected60 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0024 events3 affected60 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0024 events1 affected60 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0012 events2 affected34 at risk EG0021 events1 affected60 at risk
Magnesium metabolism disorder	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Bone disorder	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0024 events2 affected60 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0014 events1 affected34 at risk EG0020 events0 affected60 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0020 events0 affected60 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0021 events1 affected60 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0014 events2 affected34 at risk EG0022 events2 affected60 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0021 events1 affected60 at risk
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0020 events0 affected60 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Cerebral infarction	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Dizziness	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0017 events3 affected34 at risk EG0023 events3 affected60 at risk
Dysgeusia	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Headache	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0004 events3 affected12 at risk EG00116 events7 affected34 at risk EG00210 events10 affected60 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Insomnia	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0022 events2 affected60 at risk
Haematuria	Renal and urinary disorders	MedDRA 26.1	Systematic Assessment	EG0006 events3 affected12 at risk EG0013 events3 affected34 at risk EG0026 events4 affected60 at risk
Oliguria	Renal and urinary disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected12 at risk EG0014 events2 affected34 at risk EG0023 events3 affected60 at risk
Proteinuria	Renal and urinary disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Renal impairment	Renal and urinary disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0020 events0 affected60 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Gynaecomastia	Reproductive system and breast disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Scrotal inflammation	Reproductive system and breast disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events1 affected60 at risk
Vulvovaginal inflammation	Reproductive system and breast disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected34 at risk EG0026 events4 affected60 at risk
Tachycardia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events1 affected34 at risk EG0020 events0 affected60 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Nasal mucosal erosion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Nasal obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0024 events4 affected60 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0020 events0 affected60 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0021 events1 affected60 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0012 events1 affected34 at risk EG0023 events2 affected60 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Small airways disease	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Thoracic haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0024 events4 affected60 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0021 events1 affected60 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events1 affected34 at risk EG0022 events1 affected60 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected12 at risk EG0011 events1 affected34 at risk EG0025 events4 affected60 at risk
Haemorrhage subcutaneous	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG00212 events8 affected60 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events2 affected34 at risk EG0025 events3 affected60 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0005 events4 affected12 at risk EG0010 events0 affected34 at risk EG0022 events1 affected60 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0016 events6 affected34 at risk EG00211 events8 affected60 at risk
Skin haemorrhage	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Skin mass	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Ventricular hypertrophy	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Haematoma	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Haemorrhage	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Hypertension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Hypotension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0023 events3 affected60 at risk
Peripheral venous disease	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Wandering pacemaker	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Deafness	Ear and labyrinth disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Otolithiasis	Ear and labyrinth disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Thyroid mass	Endocrine disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Cataract	Eye disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Dacryostenosis acquired	Eye disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Dry eye	Eye disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Eczema eyelids	Eye disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Eyelid function disorder	Eye disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Retinal haemorrhage	Eye disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0020 events0 affected60 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0015 events2 affected34 at risk EG0022 events2 affected60 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0024 events3 affected60 at risk
Abdominal wall haemorrhage	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Abnormal faeces	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Ascites	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events3 affected34 at risk EG0022 events2 affected60 at risk
Hypoglobulinaemia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Dental caries	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0016 events6 affected34 at risk EG00211 events9 affected60 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected34 at risk EG0022 events2 affected60 at risk
Eructation	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0025 events3 affected60 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Loose tooth	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0014 events4 affected34 at risk EG0024 events3 affected60 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0021 events1 affected60 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Rectal prolapse	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Toothache	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0013 events3 affected34 at risk EG0025 events5 affected60 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected34 at risk EG0021 events1 affected60 at risk
Asthenia	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0012 events2 affected34 at risk EG0020 events0 affected60 at risk
Chest discomfort	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0021 events1 affected60 at risk
Face oedema	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Fatigue	General disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0015 events5 affected34 at risk EG0026 events5 affected60 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0002 events1 affected12 at risk EG0015 events3 affected34 at risk EG0021 events1 affected60 at risk
Influenza like illness	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Oedema peripheral	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0017 events5 affected34 at risk EG0021 events1 affected60 at risk
Pain	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Peripheral swelling	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Pyrexia	General disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0015 events2 affected34 at risk EG0028 events8 affected60 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0003 events2 affected12 at risk EG0011 events1 affected34 at risk EG0025 events4 affected60 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0026 events4 affected60 at risk
Lymphadenitis	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Liver injury	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0021 events1 affected60 at risk
Bronchitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0010 events0 affected34 at risk EG0023 events3 affected60 at risk
Covid-19	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG00219 events16 affected60 at risk
Covid-19 pneumonia	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0025 events5 affected60 at risk
Conjunctivitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Coronavirus infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Dermatophytosis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Eye infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Folliculitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG0005 events3 affected12 at risk EG0016 events2 affected34 at risk EG0021 events1 affected60 at risk
Fungal infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Gastroenteritis shigella	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Gingivitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0022 events2 affected60 at risk
Hepatitis b reactivation	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Herpes virus infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0020 events0 affected60 at risk
Herpes zoster	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0011 events1 affected34 at risk EG0022 events2 affected60 at risk
Influenza	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk
Lymph gland infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected12 at risk EG0010 events0 affected34 at risk EG0021 events1 affected60 at risk

ID	Term
D020522	Lymphoma, Mantle-Cell
D015451	Leukemia, Lymphocytic, Chronic, B-Cell

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
D006402	Hematologic Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
BG001	Phase II MCL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
BG002	Phase II CLL	Participants received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase I	Participants received single dose of acalabrutinib 100 mg capsule orally on Day 1 Cycle 0 and followed by 2 days washout period and then received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.	0	12	2	12	12	12
EG001	Phase II MCL	Participants with MCL received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.	7	34	6	34	28	34
EG002	Phase II CLL	Participants with CLL received acalabrutinib 100 mg capsule orally twice daily in 28-day cycle until PD or specific treatment discontinuation criteria were met.	2	60	21	60	56	60