A Study of Ibrutinib in Combination With Bendamustine and... | NCT01611090

NCT01611090

ID	Type	Description
PCI-32765CLL3001	Other Identifier	Janssen Research & Development, LLC
2012-000600-15	EudraCT Number
U1111-1135-3745	Other Identifier	Universal Trial Number

Status Module

Name	Class
Pharmacyclics LLC.	INDUSTRY

Description Module

Detailed Description

This is a randomized (patients will be assigned by chance to study treatments), double-blind (patients and study personnel will not know the identity of study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study to determine the benefits and risks of combining ibrutinib with bendamustine and rituximab (BR) in patients with relapsed or refractory CLL/SLL following at least 1 line of prior systemic therapy. Approximately 580 patients will be randomized in a 1:1 ratio to either treatment arm A (placebo) or treatment arm B (ibrutinib 420 mg).

Study medication will be administered orally once daily on a continuous schedule. All patients will receive BR as the background therapy plus either ibrutinib or placebo for a maximum of 6 cycles, after which treatment with ibrutinib or placebo will continue until disease progression or unacceptable toxicity.

A treatment cycle will be defined as 28 days. The study will include a screening phase, a treatment phase, and a follow-up phase. Study end is defined as when either 80% of the patients have died or 5 years after the last patient is randomized into the study, whichever occurs first.

Patients in treatment arm A (placebo) who complete the treatment phase, with disease progression or (after interim analysis) meet International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for treatment, may crossover to ibrutinib treatment (as in treatment arm B), at the investigators discretion. This open-label, next-line treatment with ibrutinib will continue until disease progression, unacceptable toxicity, withdrawal from study, or until the study end, whichever occurs earlier. One interim analysis is planned for the study. Efficacy evaluations will include computed tomography scans, laboratory testing, focused physical examinations, bone marrow biopsy and aspirate, and assessment of patient-reported outcomes. In both treatment arms, samples for the development of a population-based pharmacokinetic (PK; study of what the body does to a drug) approach will be collected. Safety will be assessed throughout the study.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ibrutinib + BR	Experimental	Ibrutinib 420 mg will be administered orally once daily on a continuous schedule. All subjects will receive background therapy with bendamustine and rituximab (BR) for a maximum of 6 cycles (a cycle is defined as 28 days, with the exception of Cycle 1, which will be 29 days to allow for rituximab dosing prior to bendamustine and study medication).	Drug: Ibrutinib Drug: Bendamustine hydrochloride Drug: Rituximab
Placebo + BR	Placebo Comparator	Matching placebo will be administered orally once daily on a continuous schedule. All subjects will receive background therapy with BR for a maximum of 6 cycles (a cycle is defined as 28 days, with the exception of Cycle 1, which will be 29 days to allow for rituximab dosing prior to bendamustine and study medication).	Drug: Bendamustine hydrochloride Drug: Rituximab Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Ibrutinib	Drug	Type=exact number, unit=mg, number=420 , form=capsule, route=oral use. Capsule is taken once daily continuously.	Ibrutinib + BR

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the interval between the date of randomization and the date of disease progression or death, whichever was first reported. IWCLL 2008 criteria for PD: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other new organ infiltrates, bone lesion, ascites, or pleural effusion confirmed due to chronic lymphocytic leukemia (CLL); >=50% increase in existing lymph nodes; >=50% increase in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) or >=50% increase from nadir count confirmed on >=2 serial assessments if absolute lymphocyte count (ALC) >=30,000 per microliter and lymphocyte doubling time is rapid, unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b [Hgb] or platelets) attributable to CLL; and transformation to a more aggressive histology.	Up to 5 years

Secondary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	ORR defined as number of participants achieving a complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR) or partial response (PR). IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.510^9/liter (L), platelets >10010^9/L, Hgb >11 gram per deciliter (g/dL) and absolute lymphocyte count <4000/microliter (mcL); CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR-2 of the following when abnormal at baseline: >=50% decrease in ALC, >=50% decrease in sum products of up to 6 lymph nodes, >=50% decrease in enlargement of spleen or liver; and 1 of the following: neutrophils >1.510^9/L, Platelets >10010^9/L and Hgb>11 g/dL or >=50% improvement over baseline in any of these; no new enlarged nodes or new hepatosplenomegaly.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
Active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for requiring treatment
Measurable nodal disease by computed tomography
Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy consisting of at least 2 cycles of a chemotherapy-containing regimen
Eastern Cooperative Oncology Group Performance Status score of 0 or 1
Hematology and biochemical values within protocol-defined limits
Agrees to protocol-defined use of effective contraception
Women of childbearing potential must have negative blood or urine pregnancy test at screening

Exclusion Criteria:

Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks (immunotherapy)
Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior randomization in any other clinical study evaluating ibrutinib
The presence of deletion of the short arm of chromosome 17
Patients previously treated with a bendamustine-containing regimen who did not achieve a response or who relapsed and required treatment within 24 months of treatment with that regimen
Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
Received a hematopoietic stem cell transplant
Known central nervous system leukemia/lymphoma or Richter's transformation
Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
Chronic use of corticosteroids
History of prior malignancy, except: malignancy treated with curative intent and with no known active disease present for >=3 years before randomization; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease
History of stroke or intracranial hemorrhage within 6 months prior to randomization; or clinically significant cardiovascular disease
Requires anticoagulation with warfarin or equivalent vitamin K antagonists or treatment with strong CYP3A4/5 inhibitors
Known history of human immunodeficiency virus or hepatitis C, or active infection with hepatitis B or C
Any uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
A woman who is pregnant or breast feeding, or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug

Name	Affiliation	Role
Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
40266025	Derived	Abuhelwa AY, Almansour SA, Brown JR, Al-Shamsi HO, Abuhelwa Z, Kharaba Z, Bustanji Y, Semreen MH, Ali S, Alhuraiji A, McKinnon RA, Sorich MJ, Alzoubi KH, Hopkins AM. Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials. Blood Adv. 2025 Jul 22;9(14):3566-3575. doi: 10.1182/bloodadvances.2024015287.
32762271

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 21, 2017	Jan 23, 2020

Arm/Group Information

ID	Title	Description
BG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
BG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00063.7± 9.82 BG00163.3± 9.3 BG00263.5± 9.56

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00096 BG001100 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00013 BG00121 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG000264 BG001264 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

ARGENTINA

Title	Measurements
	BG0003 BG0013 BG002

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

Progression-free Survival (PFS)

PFS was defined as the interval between the date of randomization and the date of disease progression or death, whichever was first reported. IWCLL 2008 criteria for PD: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other new organ infiltrates, bone lesion, ascites, or pleural effusion confirmed due to chronic lymphocytic leukemia (CLL); >=50% increase in existing lymph nodes; >=50% increase in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) or >=50% increase from nadir count confirmed on >=2 serial assessments if absolute lymphocyte count (ALC) >=30,000 per microliter and lymphocyte doubling time is rapid, unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b [Hgb] or platelets) attributable to CLL; and transformation to a more aggressive histology.

Intent to treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Posted

Median

95% Confidence Interval

Months

Up to 5 years

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Units	Counts
Participants	OG000289 OG001289

Title

Denominators

Categories

Title	Measurements
	OG00065.12(55.43 to NA)Here, NA indicates upper limit of confidence interval (CI) was not estimable due to insufficient number of events. OG00114.32(13.86 to 16.62)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		< 0.0001		Hazard Ratio (HR)	0.229			2-Sided	95	0.183	0.286					Superiority

Secondary

Overall Response Rate (ORR)

ORR defined as number of participants achieving a complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR) or partial response (PR). IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 gram per deciliter (g/dL) and absolute lymphocyte count <4000/microliter (mcL); CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR-2 of the following when abnormal at baseline: >=50% decrease in ALC, >=50% decrease in sum products of up to 6 lymph nodes, >=50% decrease in enlargement of spleen or liver; and 1 of the following: neutrophils >1.5*10^9/L, Platelets >100*10^9/L and Hgb>11 g/dL or >=50% improvement over baseline in any of these; no new enlarged nodes or new hepatosplenomegaly.

Intent to treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Posted

Number

Percentage of participants

Up to 5 years

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001

Secondary

Overall Survival (OS)

OS was defined as the interval between the date of randomization and the date of death from any cause.

Intent to treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Posted

Median

95% Confidence Interval

Months

Up to 5 years

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Units	Counts
Participants

Secondary

Percentage of Participants With Minimal Residual Disease (MRD)-Negative Response

MRD-negative response was defined as the percentage of participants who reach MRD negative disease status (less than 1 chronic lymphocytic leukemia [CLL] cell per 10,000 leukocytes) in either bone marrow or peripheral blood. All randomized participants were included in this analysis. Participants with missing MRD data were considered non-responders.

Intent to treat (ITT) population included all participants randomized into the study regardless of treatment actually received.

Posted

Number

Percentage of participants

Up to 5 years

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Secondary

Percentage of Participants With Sustained Hematologic Improvement

Sustained hematologic improvement was defined as hematological improvement that was sustained continuously for greater than or equal to (>=) 56 days without blood transfusion or growth factors: 1) Platelet counts greater than (>)100* 109/liter (L) if baseline less than or equal to (<=) 100*109/L or increase >= 50 percent (%) over baseline; 2) Hemoglobin >11 gram per deciliters (g/dL) if baseline <= 11 g/dL or increase >= 2 g/dL over baseline.

ITT population included all participants randomized into the study regardless of treatment actually received.

Posted

Number

Percentage of Participants

Up to 5 years

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Secondary

Median Time to Clinically Meaningful Improvement in FACIT-Fatigue Scale

Time to improvement is defined as the time interval (months) from randomization to the first observation of improvement. FACIT-Fatigue is an instrument for use as a measure of the effect of fatigue in patients with cancer and other chronic diseases. Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

ITT population included all participants randomized into the study regardless of treatment actually received.

Posted

Number

95% Confidence Interval

Months

Up to 2 years

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Secondary

Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms

The disease-related symptoms included fatigue, weight loss, fevers, night sweats, abdominal discomfort/splenomegaly and anorexia.

ITT population included all participants randomized into the study regardless of treatment actually received.

Posted

Count of Participants

Participants

From the date of randomization to disease progression (Up to 2 years)

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Units	Counts

Secondary

Number of Participants Who Received Subsequent Antineoplastic Therapy

Number of participants who received subsequent antineoplastic therapy was reported.

Safety analysis set included all the randomized participants who received at least 1 dose of study drug or placebo.

Posted

Count of Participants

Participants

Up to 5 years

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Units	Counts
Participants

Secondary

Change From Baseline in Beta2 Microglobulin at End of Treatment (EOT)

Change from baseline in beta2 microglobulin at end of treatment at time of primary analysis was reported.

ITT population included all participants randomized into the study regardless of treatment actually received. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this endpoint.

Posted

Mean

Standard Deviation

milligram per liter (mg/L)

Baseline to EOT (Up to 2 years)

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Units	Counts

Secondary

Change From Baseline in FACIT-Fatigue Scale at End of Treatment

FACIT-Fatigue is an instrument for use as a measure of the effect of fatigue in patients with cancer and other chronic diseases. Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

Posted

Mean

Standard Deviation

Units on a scale

Baseline to EOT (up to 2 years)

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Secondary

Change From Baseline in EORTC QLQ-C30 Physical Functioning Score at End of Treatment

EORTC QLQ-C30 Physical Functioning Score is a questionnaire to assess quality of life of cancer patients. It is composed of 30 items, multi-item measure (28 items) and 2 single-item measures. For the multiple item measure, 4-point scale is used and the score for each item range from "1 = not at all" to "4 = very much". Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which was rated on a 7-point scale ranging from "1 = very poor" to "7 = excellent". Lower scores indicate worsening. All scale and item scores were linearly transformed to be in range from 0-100. A higher score represents a higher (better) level of functioning, or a higher (worse) level of symptoms.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to EOT (up to 2 years)

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR

Secondary

Change From Baseline in EORTC QLQ-CLL 16 Domain Scores at End of Treatment

The EORTC QLQ-CLL 16 is a 16-item disease specific module that comprises 5 domains of patient-reported health status important in CLL. There are three multi-item scales that include fatigue (2 items), treatment side effects and disease symptoms (8 items), and infection (4 items), and 2 single-item scales on social activities and future health worries. Responses are measured on a 4 point scale ranging from 1 (not at all) to 4 (very much).

Posted

Mean

Standard Deviation

Units on the scale

Baseline to EOT (up to 2 years)

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Secondary

Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Visual Analog Scale at End of Treatment

The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).

Posted

Mean

Standard Deviation

Units on a scale

Baseline to EOT (up to 2 years)

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Secondary

Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Utility Score Scale at End of Treatment

The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1. High score indicating a high level of utility.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to EOT (up to 2 years)

ID	Title	Description
OG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.
OG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ibrutinib+BR	Participants received ibrutinib 420 milligram (mg) (3 * 140 mg capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles ibrutinib alone was administered until disease progression or unacceptable toxicity.	74	287	198	287	268	287
EG001	Placebo+BR	Participants received placebo (3 capsules) orally once daily starting on Cycle 1 Day 2 for a maximum of 6 cycles (each cycle of 28 days except Cycle 1 which was of 29 days) along with BR. After 6 cycles placebo alone was administered until disease progression or unacceptable toxicity.	107	287	127	287	271	287
EG002	Crossover to Ibrutinib	Participants in the placebo+BR treatment group could cross over to receive next-line ibrutinib treatment (420 mg [3 * 140 mg capsules] orally once daily on a 28-day cycle) at the discretion of the investigator at the time of disease progression or if International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for treatment were met.	57	183	105	183	157	183

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0017 affected287 at risk EG0022 affected183 at risk
Aplasia Pure Red Cell	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Aplastic Anaemia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Autoimmune Haemolytic Anaemia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0015 affected287 at risk EG0020 affected183 at risk
Bone Marrow Failure	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cytopenia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00030 affected287 at risk EG00122 affected287 at risk EG0022 affected183 at risk
Haemolytic Anaemia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Immune Thrombocytopenic Purpura	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0007 affected287 at risk EG0016 affected287 at risk EG0020 affected183 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0004 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Acute Coronary Syndrome	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0013 affected287 at risk EG0021 affected183 at risk
Angina Pectoris	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0004 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Angina Unstable	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Arrhythmia Supraventricular	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00016 affected287 at risk EG0012 affected287 at risk EG0026 affected183 at risk
Atrial Flutter	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Atrioventricular Block	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cardiac Arrest	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0023 affected183 at risk
Cardiac Failure	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cardio-Respiratory Arrest	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cardiopulmonary Failure	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Cardiovascular Insufficiency	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Carditis	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Coronary Artery Occlusion	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Myocardial Infarction	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0012 affected287 at risk EG0022 affected183 at risk
Myocarditis	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pericardial Effusion	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Sinus Node Dysfunction	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Sinus Tachycardia	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Tachycardia	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Ventricular Fibrillation	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Ventricular Flutter	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Ventricular Tachycardia	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Addison's Disease	Endocrine disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Goitre	Endocrine disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cataract	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Maculopathy	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Retinal Haemorrhage	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Scleral Disorder	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Vitreous Adhesions	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Vitreous Haemorrhage	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Abdominal Hernia	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Abdominal Incarcerated Hernia	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0023 affected183 at risk
Anal Fistula	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Ascites	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Colitis	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Colitis Ischaemic	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0004 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Duodenal Ulcer Haemorrhage	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Dysphagia	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Gastric Haemorrhage	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Gastric Ulcer Perforation	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Gastritis	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Gastrointestinal Disorder	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Gastrointestinal Inflammation	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Haematemesis	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Haematochezia	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Inguinal Hernia	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0004 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Intestinal Obstruction	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Intra-Abdominal Haemorrhage	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Large Intestine Perforation	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Lower Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Mouth Ulceration	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Oesophageal Ulcer	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Pancreatitis Acute	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Proctitis	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Small Intestinal Obstruction	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Stomatitis	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Volvulus	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0012 affected287 at risk EG0021 affected183 at risk
Asthenia	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Chest Pain	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Chills	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Complication Associated with Device	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Condition Aggravated	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Death	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Disease Progression	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Fatigue	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
General Physical Health Deterioration	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Hernia	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Influenza Like Illness	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Infusion Site Extravasation	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Malaise	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Mucosal Inflammation	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Multiple Organ Dysfunction Syndrome	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0013 affected287 at risk EG0023 affected183 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Oedema Peripheral	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pneumatosis	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pyrexia	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00011 affected287 at risk EG0017 affected287 at risk EG0024 affected183 at risk
Sudden Cardiac Death	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Sudden Death	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Systemic Inflammatory Response Syndrome	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cholangitis	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Cholecystitis Acute	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Cholecystitis Chronic	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Cholestasis	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Gallbladder Obstruction	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Hepatic Cirrhosis	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Hepatitis Toxic	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Hepatocellular Injury	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Hepatosplenomegaly	Hepatobiliary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Anaphylactic Reaction	Immune system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Abscess Jaw	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Actinomycotic Pulmonary Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Acute Sinusitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Appendicitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Arthritis Bacterial	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Ascariasis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Atypical Pneumonia	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Bacteraemia	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Brain Abscess	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Breast Abscess	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Breast Cellulitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Bronchitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0008 affected287 at risk EG0015 affected287 at risk EG0021 affected183 at risk
Bronchopulmonary Aspergillosis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0022 affected183 at risk
Campylobacter Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cellulitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0004 affected287 at risk EG0012 affected287 at risk EG0021 affected183 at risk
Cellulitis Staphylococcal	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Central Nervous System Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Chronic Sinusitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Clostridium Difficile Colitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Clostridium Difficile Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Conjunctivitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Cystitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Cytomegalovirus Colitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Cytomegalovirus Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Dacryocystitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Dermo-Hypodermitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Disseminated Cryptococcosis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Epstein-Barr Virus Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Erysipelas	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0023 affected183 at risk
Escherichia Sepsis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Escherichia Urinary Tract Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Fungal Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Gastroenteritis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Gastroenteritis Viral	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Gastrointestinal Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Haemophilus Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Hepatitis B Reactivation	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Herpes Zoster	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0012 affected287 at risk EG0021 affected183 at risk
Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Infectious Pleural Effusion	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Influenza	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Laryngitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0012 affected287 at risk EG0022 affected183 at risk
Lung Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0013 affected287 at risk EG0020 affected183 at risk
Lymphadenitis Bacterial	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Muscle Abscess	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Neutropenic Sepsis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Nocardiosis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Oral Candidiasis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Osteomyelitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Otitis Media	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Periodontitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Periorbital Cellulitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Peritonsillar Abscess	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Pharyngeal Abscess	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Pharyngitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Pharyngitis Streptococcal	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pneumocystis Jirovecii Pneumonia	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pneumonia	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00048 affected287 at risk EG00126 affected287 at risk EG00234 affected183 at risk
Pneumonia Bacterial	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Pneumonia Haemophilus	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pneumonia Pneumococcal	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Pneumonia Streptococcal	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0022 affected183 at risk
Progressive Multifocal Leukoencephalopathy	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Pseudomembranous Colitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pulmonary Tuberculoma	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pulmonary Tuberculosis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pyelonephritis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Rash Pustular	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Respiratory Syncytial Virus Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0005 affected287 at risk EG0012 affected287 at risk EG0025 affected183 at risk
Sepsis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0008 affected287 at risk EG0014 affected287 at risk EG0024 affected183 at risk
Septic Shock	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0006 affected287 at risk EG0012 affected287 at risk EG0025 affected183 at risk
Sinusitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0012 affected287 at risk EG0022 affected183 at risk
Skin Candida	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Skin Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Soft Tissue Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Splenic Abscess	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Staphylococcal Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Staphylococcal Skin Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Subcutaneous Abscess	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Tooth Abscess	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Tuberculosis of Central Nervous System	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0013 affected287 at risk EG0020 affected183 at risk
Urinary Tract Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0006 affected287 at risk EG0011 affected287 at risk EG0022 affected183 at risk
Urosepsis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Varicella	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Varicella Zoster Virus Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Viral Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Abdominal Injury	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Ankle Fracture	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Femoral Neck Fracture	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Femur Fracture	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Hip Fracture	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Incision Site Haemorrhage	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Infusion Related Reaction	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0004 affected287 at risk EG0015 affected287 at risk EG0020 affected183 at risk
Pelvic Fracture	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pneumoconiosis	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pneumothorax Traumatic	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Post Procedural Haemorrhage	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Post Procedural Swelling	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Subdural Haematoma	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Thoracic Vertebral Fracture	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Biopsy	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Blood Creatinine Increased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Body Temperature Increased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Neutrophil Count Decreased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Prostatic Specific Antigen Increased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Weight Decreased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Diabetes Mellitus	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Tumour Lysis Syndrome	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0006 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Chondrocalcinosis Pyrophosphate	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Femoroacetabular Impingement	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Groin Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Lumbar Spinal Stenosis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Muscle Haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Acute Lymphocytic Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Adenosquamous Cell Lung Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Anal Squamous Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Basal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0005 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Bladder Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Bronchioloalveolar Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Chronic Myelomonocytic Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Intestinal Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Intraductal Papilloma of Breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Lung Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Malignant Melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Malignant Melanoma in Situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Maxillofacial Sinus Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Metastases to Central Nervous System	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Metastatic Renal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Myelodysplastic Syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Myeloproliferative Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Neuroendocrine Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0022 affected183 at risk
Renal Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Renal Cancer Stage I	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Renal Oncocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Squamous Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0011 affected287 at risk EG0022 affected183 at risk
Squamous Cell Carcinoma of Skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Superficial Spreading Melanoma Stage Unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Transitional Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Carotid Sinus Syndrome	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cerebral Disorder	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Cerebral Infarction	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Cerebral Ischaemia	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Cognitive Disorder	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Depressed Level of Consciousness	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Encephalopathy	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Facial Paresis	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Haemorrhage Intracranial	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Haemorrhagic Stroke	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Headache	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Loss of Consciousness	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Meningism	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Peripheral Sensory Neuropathy	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Post Herpetic Neuralgia	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Radiculopathy	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Syncope	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Transient Global Amnesia	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Vascular Encephalopathy	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Acute Stress Disorder	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Alcoholic Psychosis	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Completed Suicide	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Confusional State	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Delirium	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Mental Status Changes	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Acute Kidney Injury	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Calculus Bladder	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Dysuria	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Haematuria	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Nephropathy	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Nephropathy Toxic	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Renal Failure	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0022 affected183 at risk
Renal Impairment	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Ureteric Stenosis	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Urge Incontinence	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Urinary Incontinence	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Urinary Retention	Renal and urinary disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Benign Prostatic Hyperplasia	Reproductive system and breast disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Fibrocystic Breast Disease	Reproductive system and breast disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Genital Rash	Reproductive system and breast disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pelvic Floor Muscle Weakness	Reproductive system and breast disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Penile Dysplasia	Reproductive system and breast disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Uterine Haemorrhage	Reproductive system and breast disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Uterine Prolapse	Reproductive system and breast disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0013 affected287 at risk EG0020 affected183 at risk
Dyspnoea Exertional	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Lung Infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0003 affected287 at risk EG0012 affected287 at risk EG0022 affected183 at risk
Pleuritic Pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0021 affected183 at risk
Pulmonary Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pulmonary Mass	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Pulmonary Sarcoidosis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0023 affected183 at risk
Respiratory Tract Oedema	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Sleep Apnoea Syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Acute Febrile Neutrophilic Dermatosis	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Cellulitis	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Drug Eruption	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Excessive Granulation Tissue	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Hypersensitivity Vasculitis	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Pemphigoid	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Pemphigus	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0012 affected287 at risk EG0020 affected183 at risk
Rash Erythematous	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Skin Necrosis	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Aortic Aneurysm Rupture	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Arterial Stenosis	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0013 affected287 at risk EG0020 affected183 at risk
Haematoma	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Hypertension	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0021 affected183 at risk
Hypertensive Crisis	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Hypotension	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0002 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Jugular Vein Thrombosis	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Lymphoedema	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Peripheral Arterial Occlusive Disease	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Peripheral Artery Occlusion	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Peripheral Artery Thrombosis	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Peripheral Ischaemia	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Thrombophlebitis	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk
Thrombosis	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0001 affected287 at risk EG0010 affected287 at risk EG0020 affected183 at risk
Vasculitis	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0000 affected287 at risk EG0011 affected287 at risk EG0020 affected183 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00073 affected287 at risk EG00179 affected287 at risk EG00233 affected183 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00015 affected287 at risk EG00118 affected287 at risk EG0022 affected183 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG000170 affected287 at risk EG001159 affected287 at risk EG00240 affected183 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00090 affected287 at risk EG00169 affected287 at risk EG00224 affected183 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00023 affected287 at risk EG0015 affected287 at risk EG00219 affected183 at risk
Cataract	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00020 affected287 at risk EG0013 affected287 at risk EG0028 affected183 at risk
Dry Eye	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00015 affected287 at risk EG0019 affected287 at risk EG0026 affected183 at risk
Vision Blurred	Eye disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00019 affected287 at risk EG00119 affected287 at risk EG0023 affected183 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00039 affected287 at risk EG00124 affected287 at risk EG0023 affected183 at risk
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00023 affected287 at risk EG00116 affected287 at risk EG00211 affected183 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00061 affected287 at risk EG00150 affected287 at risk EG00215 affected183 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG000115 affected287 at risk EG00168 affected287 at risk EG00247 affected183 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00024 affected287 at risk EG00121 affected287 at risk EG0028 affected183 at risk
Gastroesophageal Reflux Disease	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00015 affected287 at risk EG00112 affected287 at risk EG0024 affected183 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG000108 affected287 at risk EG001101 affected287 at risk EG00216 affected183 at risk
Toothache	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00015 affected287 at risk EG0015 affected287 at risk EG0023 affected183 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00042 affected287 at risk EG00145 affected287 at risk EG00215 affected183 at risk
Asthenia	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00026 affected287 at risk EG00124 affected287 at risk EG0025 affected183 at risk
Chills	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00033 affected287 at risk EG00131 affected287 at risk EG0025 affected183 at risk
Fatigue	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00069 affected287 at risk EG00166 affected287 at risk EG00232 affected183 at risk
Influenza Like Illness	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG0009 affected287 at risk EG00110 affected287 at risk EG00212 affected183 at risk
Mucosal Inflammation	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00015 affected287 at risk EG0017 affected287 at risk EG0023 affected183 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00017 affected287 at risk EG00113 affected287 at risk EG0023 affected183 at risk
Oedema Peripheral	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00049 affected287 at risk EG00134 affected287 at risk EG00221 affected183 at risk
Pyrexia	General disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00074 affected287 at risk EG00160 affected287 at risk EG00222 affected183 at risk
Bronchitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00051 affected287 at risk EG00129 affected287 at risk EG00219 affected183 at risk
Cellulitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00016 affected287 at risk EG0018 affected287 at risk EG00210 affected183 at risk
Conjunctivitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00020 affected287 at risk EG00115 affected287 at risk EG00210 affected183 at risk
Herpes Zoster	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00024 affected287 at risk EG00117 affected287 at risk EG0027 affected183 at risk
Influenza	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00022 affected287 at risk EG00116 affected287 at risk EG0027 affected183 at risk
Oral Herpes	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00015 affected287 at risk EG00118 affected287 at risk EG0027 affected183 at risk
Pharyngitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00018 affected287 at risk EG00113 affected287 at risk EG0022 affected183 at risk
Pneumonia	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00040 affected287 at risk EG00125 affected287 at risk EG00221 affected183 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00019 affected287 at risk EG00110 affected287 at risk EG00215 affected183 at risk
Sinusitis	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00038 affected287 at risk EG00124 affected287 at risk EG00225 affected183 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00069 affected287 at risk EG00150 affected287 at risk EG00236 affected183 at risk
Urinary Tract Infection	Infections and infestations	MedDRA Version 20.0	Non-systematic Assessment	EG00028 affected287 at risk EG00115 affected287 at risk EG00226 affected183 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG00030 affected287 at risk EG0019 affected287 at risk EG00215 affected183 at risk
Infusion Related Reaction	Injury, poisoning and procedural complications	MedDRA Version 20.0	Non-systematic Assessment	EG00045 affected287 at risk EG00164 affected287 at risk EG0021 affected183 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG00015 affected287 at risk EG00112 affected287 at risk EG0023 affected183 at risk
Blood Creatinine Increased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG00017 affected287 at risk EG0017 affected287 at risk EG0026 affected183 at risk
Neutrophil Count Decreased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG00021 affected287 at risk EG00116 affected287 at risk EG0023 affected183 at risk
Platelet Count Decreased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG00017 affected287 at risk EG0019 affected287 at risk EG0022 affected183 at risk
Weight Decreased	Investigations	MedDRA Version 20.0	Non-systematic Assessment	EG00018 affected287 at risk EG00118 affected287 at risk EG0025 affected183 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00042 affected287 at risk EG00142 affected287 at risk EG00216 affected183 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00036 affected287 at risk EG00120 affected287 at risk EG0027 affected183 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00024 affected287 at risk EG00112 affected287 at risk EG0028 affected183 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00047 affected287 at risk EG00129 affected287 at risk EG00225 affected183 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00041 affected287 at risk EG00122 affected287 at risk EG00223 affected183 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00044 affected287 at risk EG00114 affected287 at risk EG00217 affected183 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00028 affected287 at risk EG00115 affected287 at risk EG0029 affected183 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00021 affected287 at risk EG00115 affected287 at risk EG00212 affected183 at risk
Dysgeusia	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00015 affected287 at risk EG00115 affected287 at risk EG0023 affected183 at risk
Headache	Nervous system disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00049 affected287 at risk EG00147 affected287 at risk EG00218 affected183 at risk
Anxiety	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00022 affected287 at risk EG00111 affected287 at risk EG0029 affected183 at risk
Depression	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00018 affected287 at risk EG0018 affected287 at risk EG0024 affected183 at risk
Insomnia	Psychiatric disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00027 affected287 at risk EG00121 affected287 at risk EG00210 affected183 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00074 affected287 at risk EG00175 affected287 at risk EG00227 affected183 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00022 affected287 at risk EG00129 affected287 at risk EG00211 affected183 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00022 affected287 at risk EG00110 affected287 at risk EG00215 affected183 at risk
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00016 affected287 at risk EG0019 affected287 at risk EG0024 affected183 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00030 affected287 at risk EG00120 affected287 at risk EG0028 affected183 at risk
Productive Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00021 affected287 at risk EG00118 affected287 at risk EG0029 affected183 at risk
Viral Upper Respiratory Tract Infection	Respiratory, thoracic and mediastinal disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00030 affected287 at risk EG00120 affected287 at risk EG00213 affected183 at risk
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00027 affected287 at risk EG00117 affected287 at risk EG0027 affected183 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00014 affected287 at risk EG0012 affected287 at risk EG00210 affected183 at risk
Onychoclasis	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00010 affected287 at risk EG0010 affected287 at risk EG00210 affected183 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00034 affected287 at risk EG00133 affected287 at risk EG0029 affected183 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00063 affected287 at risk EG00135 affected287 at risk EG00215 affected183 at risk
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00017 affected287 at risk EG00111 affected287 at risk EG0027 affected183 at risk
Skin Lesion	Skin and subcutaneous tissue disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00030 affected287 at risk EG0015 affected287 at risk EG00211 affected183 at risk
Haematoma	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00026 affected287 at risk EG0013 affected287 at risk EG00214 affected183 at risk
Hypertension	Vascular disorders	MedDRA Version 20.0	Non-systematic Assessment	EG00047 affected287 at risk EG00114 affected287 at risk EG00227 affected183 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Birmingham	Alabama		United States

ID	Term
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D012008	Recurrence

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

ID	Term
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Term
C551803	ibrutinib
D000069461	Bendamustine Hydrochloride
D000069283	Rituximab