Decitabine With or Without Bortezomib in Treating Older P... | NCT01420926

ID	Type	Description	Link
NCI-2011-02987	Registry Identifier	CTRP (Clinical Trial Reporting Program)
CDR0000709218
CALGB-11002	Other Identifier	Alliance for Clinical Trials in Oncology
CALGB-11002	Other Identifier	CTEP
U10CA180821	U.S. NIH Grant/Contract		View source
U10CA031946	U.S. NIH Grant/Contract		View source

Description Module

Detailed Description

PRIMARY OBJECTIVE:

I. To determine if treatment of older acute myeloid leukemia (AML) patients with decitabine and bortezomib significantly improves the overall survival times of older AML patients compared with decitabine alone.

SECONDARY OBJECTIVES:

I. To determine the rate of complete remission (CR and CR + incomplete blood count recovery [CRi]) for each of the 2 treatment regimens in the proposal.

II. To determine the overall survival, progression-free survival, disease-free survival and for each of the treatment regimens on this study.

III. To determine whether ongoing treatment with these regimens prolongs overall survival even in the absence of complete remission.

IV. To describe the frequency and severity of adverse events, as well as the tolerability of each of these regimens in patients treated on this study.

V. To describe the interaction of pretreatment disease and patient characteristics including morphology, cytogenetics, molecular genetics, white blood cell (WBC) count, blood and bone marrow blast count, age, performance status and comprehensive geriatric assessment on clinical outcomes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: REMISSION INDUCTION THERAPY: Patients receive decitabine intravenously (IV) over 1 hour once daily (QD) on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CR with CRi proceed to continuation therapy. Patients achieving CR or CR with CRi proceed to maintenance therapy.

CONTINUATION THERAPY: Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: REMISSION INDUCTION THERAPY: Patients receive decitabine IV over 1 hour QD on days 2-11 and bortezomib subcutaneously (SC) on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CR with CRi proceed to maintenance therapy.

CONTINUATION THERAPY: Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive bortezomib SC on day 1 and decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 2 years, every 3 months for 2 years, and then once a year for a maximum of 10 years from study entry.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A (decitabine)	Experimental	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Decitabine Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Quality-of-Life Assessment Other: Questionnaire Administration
Arm B (decitabine and bortezomib)	Experimental	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Bortezomib Drug: Decitabine Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Quality-of-Life Assessment Other: Questionnaire Administration

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bortezomib	Drug	Given SC	Arm B (decitabine and bortezomib)	[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid

Measure	Description	Time Frame
Overall Survival (OS) Time	Overall survival (OS) was defined as the time from study entry to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.	48 months

Measure	Description	Time Frame
Complete Remission Rate (CR and CRi)	Defined as the number of patients who achieve a CR or CRi divided by the total number of evaluable patients. A Complete remission (CR) requires: <5% marrow blast, > 200 nucleated cells, no blasts with auer rods, no extramedullary disease, ANC >1,000/mm^3 and platelets > 100,000/mm^3. A CR with incomplete blood count recovery (CRi) is defined as CR with exception of ANC < 1,000/mm^3 or platelets < 100,000/mm^3.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Unequivocal pathologic diagnosis of AML (>= 20% blasts in the bone marrow based on World Health Organization [WHO] criteria) EXCLUDING:
- Acute promyelocytic leukemia t(15;17)(q22;q12); PML-RARA
- Acute myeloid leukemia with t(8;21)(q22;q22); RUNX1-RUNXT1 as determined by the Ohio State University (OSU) Molecular Reference Laboratory, per Cancer and Leukemia Group B (CALGB) 20202; however patients who (1) are >= 75 years; and/or (2) have an ejection fraction of < 40%; and/or (3) have a performance status of > 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and core-binding factor (CBF) molecular screening results from CALGB 20202
- Acute myeloid leukemia with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11 as determined by the OSU Molecular Reference Laboratory, per CALGB 20202; however patients who (1) are >= 75 years; and/or (2) have an ejection fraction of < 40%; and/or (3) have a performance status of > 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and CBF molecular screening results from CALGB 20202
Absence of FLT3 mutation (ITD or point mutation) determined by the OSU Molecular Reference Laboratory, per CALGB 20202; however patients who (1) are >= 75 years; and/or (2) have an ejection fraction of < 40%; and/or (3) have a performance status of > 2, may be registered to CALGB 20202 and registered and treated on CALGB 11002 prior to receiving the FLT3 mutation and CBF molecular screening results from CALGB 20202
No prior treatment for AML except:
- Emergency leukapheresis
- Emergency treatment for hyperleukocytosis with hydroxyurea
- Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis (one dose only)
- Growth factor/cytokine support
AML patients with an antecedent hematologic disorder (AHD) or myelodysplastic syndrome (MDS) are eligible for this trial provided that they have not received treatment for their AHD or MDS with cytotoxic chemotherapy (e.g., cytarabine, daunorubicin, etc.), decitabine, or bortezomib; patients may have been previously treated with azacitidine if their last dose was >= 90 days prior to starting 11002
AML patients with therapy-related myeloid neoplasms (t-MN) are eligible if they have not received radiation therapy or chemotherapy (not including hormonal therapy) for their primary malignancy or disorder for > 6 months

Name	Affiliation	Role
Gail J Roboz	Alliance for Clinical Trials in Oncology	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Palo Alto Medical Foundation-Camino Division		Mountain View	California	94040	United States
Hartford Hospital

PubMed Identifier	Type	Citation	Retractions
36184192	Derived	Seffernick AE, Mrozek K, Nicolet D, Stone RM, Eisfeld AK, Byrd JC, Archer KJ. High-dimensional genomic feature selection with the ordered stereotype logit model. Brief Bioinform. 2022 Nov 19;23(6):bbac414. doi: 10.1093/bib/bbac414.
35420672	Derived	Ritchie EK, Klepin HD, Storrick E, Major B, Le-Rademacher J, Wadleigh M, Walker A, Larson RA, Roboz GJ. Geriatric assessment for older adults receiving less-intensive therapy for acute myeloid leukemia: report of CALGB 361101. Blood Adv. 2022 Jun 28;6(12):3812-3820. doi: 10.1182/bloodadvances.2021006872.

ID	Title	Description
FG000	Arm I (Decitabine)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Overall Survival (OS) Time

Overall survival (OS) was defined as the time from study entry to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.

Posted

Median

95% Confidence Interval

months

48 months

ID	Title	Description
OG000	Arm I (Decitabine)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
OG001	Arm II (Decitabine and Bortezomib)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Units	Counts
Participants	OG00082 OG00181

Title

Denominators

Categories

Title	Measurements
	OG0009.3(5.8 to 12.2) OG0018.8(3.8 to 14.3)

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		Stratified 1-sided log-rank		0.30														Superiority or Other (legacy)

Secondary

Complete Remission Rate (CR and CRi)

Defined as the number of patients who achieve a CR or CRi divided by the total number of evaluable patients. A Complete remission (CR) requires: <5% marrow blast, > 200 nucleated cells, no blasts with auer rods, no extramedullary disease, ANC >1,000/mm^3 and platelets > 100,000/mm^3. A CR with incomplete blood count recovery (CRi) is defined as CR with exception of ANC < 1,000/mm^3 or platelets < 100,000/mm^3.

Posted

Number

95% Confidence Interval

percentage of participants

48 months

ID	Title	Description
OG000	Arm I (Decitabine)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
OG001	Arm II (Decitabine and Bortezomib)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Secondary

Disease-free Survival (DFS)

Disease free survival (DFS) was defined as the time from CR to relapse or death. Relapse free and surviving patients were censored at the date of last follow-up. The median DFS with 95% CI was estimated using the Kaplan Meier method. Relapse is defined as the reappearance of blood blasts or >= 5% marrow blasts after achieving a CR or CRi.

Only participants who achieved a CR are included in this analysis.

Posted

Median

95% Confidence Interval

months

48 months

ID	Title	Description
OG000	Arm I (Decitabine)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
OG001	Arm II (Decitabine and Bortezomib)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Secondary

Progression-free Survival

Progression free survival (PFS) was defined as the time from study entry to progression or death. Progression free and surviving patients were censored at the date of last follow-up. The median DFS with 95% CI was estimated using the Kaplan Meier method.

Posted

Median

95% Confidence Interval

months

48 months

ID	Title	Description
OG000	Arm I (Decitabine)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
OG001	Arm II (Decitabine and Bortezomib)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Secondary

Adverse Events

Adverse Events: Incidence of adverse events, assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events were collected every cycle during treatment and up to one month after treatment. Adverse events were summarized using summary statistics and frequency tables for each separate cohort. Per protocol, analysis was descriptive in nature. In this section, the number of patients that reported a grade 4 or higher event are summarized. A complete listing of Adverse Events is provided in the Adverse Events section below.

The 4 participants were not evaluated for adverse events were excluded from this analysis.

Posted

Number

participants

48 months

ID	Title	Description
OG000	Arm I (Decitabine)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
OG001	Arm II (Decitabine and Bortezomib)

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG00051 events40 affected80 at risk EG00152 events39 affected79 at risk
Blood and lymphatic system disorders	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected79 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0004 events2 affected80 at risk EG0013 events3 affected79 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG00023 events20 affected80 at risk EG00124 events23 affected79 at risk
Thrombotic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0009 events8 affected80 at risk EG0012 events2 affected79 at risk
Atrial flutter	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Cardiac arrest	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0013 events3 affected79 at risk
Cardiac disorders - Other	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0013 events3 affected79 at risk
Chest pain - cardiac	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0013 events2 affected79 at risk
Conduction disorder	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Heart failure	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0013 events3 affected79 at risk
Left ventricular systolic dysfunction	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Myocardial infarction	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Palpitations	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Paroxysmal atrial tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Pericardial effusion	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Pericardial tamponade	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0011 events1 affected79 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG00012 events9 affected80 at risk EG00110 events7 affected79 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0006 events3 affected80 at risk EG0014 events4 affected79 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Congenital, familial and genetic disorders - Other	Congenital, familial and genetic disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hypothyroidism	Endocrine disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Blurred vision	Eye disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Eye disorders - Other	Eye disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0010 events0 affected79 at risk
Eye pain	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Floaters	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Watering eyes	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00010 events10 affected80 at risk EG0014 events4 affected79 at risk
Anal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Ascites	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Bloating	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Colitis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Colonic fistula	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Colonic perforation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Constipation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00020 events17 affected80 at risk EG00119 events16 affected79 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00017 events14 affected80 at risk EG00124 events22 affected79 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0014 events4 affected79 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Esophageal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Fecal incontinence	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Flatulence	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Gastric hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0009 events7 affected80 at risk EG0012 events2 affected79 at risk
Gastrointestinal disorders - Other	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0017 events5 affected79 at risk
Hemorrhoidal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0013 events3 affected79 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0013 events2 affected79 at risk
Ileus	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0013 events3 affected79 at risk
Intra-abdominal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Lip pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Mucositis oral	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0017 events7 affected79 at risk
Nausea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00025 events21 affected80 at risk EG00124 events21 affected79 at risk
Oral hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Oral pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0014 events4 affected79 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Toothache	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Typhlitis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00018 events16 affected80 at risk EG00117 events14 affected79 at risk
Chills	General disorders	MedDRA 12	Systematic Assessment	EG00011 events9 affected80 at risk EG0019 events8 affected79 at risk
Death NOS	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Edema face	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Edema limbs	General disorders	MedDRA 12	Systematic Assessment	EG00019 events17 affected80 at risk EG00128 events23 affected79 at risk
Edema trunk	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG00038 events29 affected80 at risk EG00135 events27 affected79 at risk
Fever	General disorders	MedDRA 12	Systematic Assessment	EG00010 events7 affected80 at risk EG00112 events9 affected79 at risk
Flu like symptoms	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
General disorders and administration site conditions - Other	General disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0013 events3 affected79 at risk
Hypothermia	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events3 affected79 at risk
Infusion related reaction	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Injection site reaction	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Localized edema	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Malaise	General disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0013 events2 affected79 at risk
Multi-organ failure	General disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0011 events1 affected79 at risk
Non-cardiac chest pain	General disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0018 events6 affected79 at risk
Pain	General disorders	MedDRA 12	Systematic Assessment	EG0008 events8 affected80 at risk EG0019 events8 affected79 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Hepatobiliary disorders - Other	Hepatobiliary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Allergic reaction	Immune system disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Abdominal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Catheter related infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0015 events5 affected79 at risk
Cecal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Esophageal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Eye infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Gum infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Infections and infestations - Other	Infections and infestations	MedDRA 12	Systematic Assessment	EG0009 events8 affected80 at risk EG00111 events11 affected79 at risk
Joint infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Lip infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Lung infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG00018 events14 affected80 at risk EG00116 events13 affected79 at risk
Mucosal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0005 events3 affected80 at risk EG0012 events2 affected79 at risk
Papulopustular rash	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Penile infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Pharyngitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events1 affected79 at risk
Pleural infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Sepsis	Infections and infestations	MedDRA 12	Systematic Assessment	EG00013 events12 affected80 at risk EG0019 events9 affected79 at risk
Sinusitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Skin infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0014 events4 affected79 at risk
Tooth infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Upper respiratory infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Urinary tract infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0013 events3 affected79 at risk
Wound infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Bruising	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0008 events8 affected80 at risk EG0014 events4 affected79 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0007 events6 affected80 at risk EG0014 events4 affected79 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Injury, poisoning and procedural complications - Other	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA 12	Systematic Assessment	EG0006 events6 affected80 at risk EG0018 events8 affected79 at risk
Alanine aminotransferase increased	Investigations	MedDRA 12	Systematic Assessment	EG00015 events13 affected80 at risk EG00119 events15 affected79 at risk
Alkaline phosphatase increased	Investigations	MedDRA 12	Systematic Assessment	EG00011 events8 affected80 at risk EG00114 events12 affected79 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 12	Systematic Assessment	EG00017 events15 affected80 at risk EG00122 events20 affected79 at risk
Blood bilirubin increased	Investigations	MedDRA 12	Systematic Assessment	EG00024 events21 affected80 at risk EG00110 events10 affected79 at risk
Cardiac troponin I increased	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0014 events4 affected79 at risk
Cholesterol high	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Creatinine increased	Investigations	MedDRA 12	Systematic Assessment	EG00017 events17 affected80 at risk EG00126 events19 affected79 at risk
Ejection fraction decreased	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Electrocardiogram QT corrected interval prolonged	Investigations	MedDRA 12	Systematic Assessment	EG0007 events6 affected80 at risk EG0016 events6 affected79 at risk
GGT increased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
INR increased	Investigations	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0017 events7 affected79 at risk
Investigations - Other	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0015 events5 affected79 at risk
Lipase increased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Lymphocyte count decreased	Investigations	MedDRA 12	Systematic Assessment	EG00018 events14 affected80 at risk EG00125 events17 affected79 at risk
Lymphocyte count increased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Neutrophil count decreased	Investigations	MedDRA 12	Systematic Assessment	EG00047 events37 affected80 at risk EG00151 events38 affected79 at risk
Platelet count decreased	Investigations	MedDRA 12	Systematic Assessment	EG00047 events39 affected80 at risk EG00148 events37 affected79 at risk
Urine output decreased	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Weight gain	Investigations	MedDRA 12	Systematic Assessment	EG0005 events4 affected80 at risk EG0016 events5 affected79 at risk
Weight loss	Investigations	MedDRA 12	Systematic Assessment	EG00012 events7 affected80 at risk EG00112 events8 affected79 at risk
White blood cell decreased	Investigations	MedDRA 12	Systematic Assessment	EG00027 events20 affected80 at risk EG00125 events18 affected79 at risk
Acidosis	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0015 events5 affected79 at risk
Alkalosis	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0011 events1 affected79 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00021 events16 affected80 at risk EG00124 events18 affected79 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0014 events4 affected79 at risk
Hypercalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00033 events24 affected80 at risk EG00133 events25 affected79 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0006 events4 affected80 at risk EG0014 events4 affected79 at risk
Hypermagnesemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0007 events5 affected80 at risk EG0014 events4 affected79 at risk
Hypernatremia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0011 events1 affected79 at risk
Hypertriglyceridemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hyperuricemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events3 affected79 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00028 events21 affected80 at risk EG00132 events26 affected79 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00021 events19 affected80 at risk EG00123 events19 affected79 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0017 events7 affected79 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00024 events17 affected80 at risk EG00129 events21 affected79 at risk
Hypomagnesemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00021 events16 affected80 at risk EG0018 events7 affected79 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00025 events20 affected80 at risk EG00122 events19 affected79 at risk
Hypophosphatemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00011 events8 affected80 at risk EG0019 events8 affected79 at risk
Iron overload	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Metabolism and nutrition disorders - Other	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected79 at risk
Tumor lysis syndrome	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0007 events6 affected80 at risk EG0012 events2 affected79 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0013 events2 affected79 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0007 events7 affected80 at risk EG0017 events7 affected79 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Buttock pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0010 events0 affected79 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0011 events1 affected79 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00016 events11 affected80 at risk EG00114 events9 affected79 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Muscle weakness upper limb	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Musculoskeletal and connective tissue disorder - Other	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0015 events5 affected79 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0011 events1 affected79 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0011 events1 affected79 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0007 events6 affected80 at risk EG0018 events8 affected79 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0016 events4 affected79 at risk
Treatment related secondary malignancy	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Ataxia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Cognitive disturbance	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0004 events1 affected80 at risk EG0010 events0 affected79 at risk
Dizziness	Nervous system disorders	MedDRA 12	Systematic Assessment	EG00010 events9 affected80 at risk EG00111 events10 affected79 at risk
Dysarthria	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Dysgeusia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0015 events4 affected79 at risk
Dysphasia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Headache	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0007 events6 affected80 at risk EG00112 events11 affected79 at risk
Intracranial hemorrhage	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0013 events3 affected79 at risk
Lethargy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected80 at risk EG0012 events2 affected79 at risk
Memory impairment	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Nervous system disorders - Other	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0014 events4 affected79 at risk
Paresthesia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events1 affected79 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG00114 events9 affected79 at risk
Presyncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Reversible posterior leukoencephalopathy syndrome	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Seizure	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events2 affected79 at risk
Sinus pain	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Somnolence	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0012 events2 affected79 at risk
Stroke	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Syncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0013 events3 affected79 at risk
Agitation	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0011 events1 affected79 at risk
Anxiety	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0007 events7 affected80 at risk EG0017 events7 affected79 at risk
Confusion	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00012 events7 affected80 at risk EG0019 events9 affected79 at risk
Delirium	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0006 events6 affected80 at risk EG0014 events4 affected79 at risk
Delusions	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Depression	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0006 events6 affected80 at risk EG0019 events6 affected79 at risk
Hallucinations	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Insomnia	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00011 events10 affected80 at risk EG00111 events10 affected79 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0016 events6 affected79 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0009 events7 affected80 at risk EG00112 events7 affected79 at risk
Hematuria	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected79 at risk
Proteinuria	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0007 events5 affected80 at risk EG0018 events8 affected79 at risk
Renal and urinary disorders - Other	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Renal calculi	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Urinary frequency	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0006 events6 affected80 at risk EG0010 events0 affected79 at risk
Urinary retention	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0013 events3 affected79 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Urinary tract pain	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Urinary urgency	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Penile pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Vaginal discharge	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Adult respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0009 events7 affected80 at risk EG0015 events4 affected79 at risk
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00024 events20 affected80 at risk EG00114 events13 affected79 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00020 events18 affected80 at risk EG00129 events23 affected79 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0015 events5 affected79 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0009 events8 affected80 at risk EG0018 events8 affected79 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0012 events2 affected79 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0009 events8 affected80 at risk EG00114 events12 affected79 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0015 events5 affected79 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Postnasal drip	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected79 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0005 events3 affected80 at risk EG0013 events3 affected79 at risk
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected80 at risk EG0015 events5 affected79 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0013 events3 affected79 at risk
Respiratory, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0014 events4 affected79 at risk
Sleep apnea	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events1 affected79 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0012 events2 affected79 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0006 events6 affected80 at risk EG0015 events3 affected79 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Erythroderma	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Nail loss	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Periorbital edema	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0014 events4 affected79 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0012 events2 affected79 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG00010 events10 affected80 at risk EG00111 events10 affected79 at risk
Skin and subcutaneous tissue disorders - Other	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0009 events6 affected80 at risk EG00112 events11 affected79 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Skin induration	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0010 events0 affected79 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Hematoma	Vascular disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Hot flashes	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hypertension	Vascular disorders	MedDRA 12	Systematic Assessment	EG0006 events5 affected80 at risk EG00112 events11 affected79 at risk
Hypotension	Vascular disorders	MedDRA 12	Systematic Assessment	EG00017 events16 affected80 at risk EG00119 events17 affected79 at risk
Superficial thrombophlebitis	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Thromboembolic event	Vascular disorders	MedDRA 12	Systematic Assessment	EG0006 events6 affected80 at risk EG0013 events3 affected79 at risk
Vascular disorders - Other	Vascular disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0010 events0 affected79 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG000253 events63 affected80 at risk EG001239 events59 affected79 at risk
Blood and lymphatic system disorders - Other	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG00013 events3 affected80 at risk EG0012 events2 affected79 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0007 events6 affected80 at risk EG0013 events3 affected79 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG00053 events34 affected80 at risk EG00145 events33 affected79 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0008 events4 affected80 at risk EG0016 events3 affected79 at risk
Thrombotic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0017 events6 affected79 at risk
Atrial flutter	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events1 affected79 at risk
Cardiac arrest	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events2 affected79 at risk
Cardiac disorders - Other	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Chest pain - cardiac	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0018 events3 affected79 at risk
Conduction disorder	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Heart failure	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0016 events4 affected79 at risk
Left ventricular systolic dysfunction	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Myocardial infarction	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Palpitations	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0013 events2 affected79 at risk
Pericardial effusion	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0017 events5 affected79 at risk
Right ventricular dysfunction	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0015 events5 affected79 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG00011 events9 affected80 at risk EG00114 events6 affected79 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Ventricular arrhythmia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0016 events6 affected79 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Ear and labyrinth disorders - Other	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0014 events1 affected79 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Endocrine disorders - Other	Endocrine disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Hyperparathyroidism	Endocrine disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hypothyroidism	Endocrine disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0016 events3 affected79 at risk
Blurred vision	Eye disorders	MedDRA 12	Systematic Assessment	EG00024 events4 affected80 at risk EG00112 events6 affected79 at risk
Conjunctivitis	Eye disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0010 events0 affected79 at risk
Dry eye	Eye disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Eye disorders - Other	Eye disorders	MedDRA 12	Systematic Assessment	EG0005 events2 affected80 at risk EG0014 events4 affected79 at risk
Eye pain	Eye disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0019 events1 affected79 at risk
Retinal vascular disorder	Eye disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Vitreous hemorrhage	Eye disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Watering eyes	Eye disorders	MedDRA 12	Systematic Assessment	EG0004 events1 affected80 at risk EG0010 events0 affected79 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0013 events2 affected79 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00010 events8 affected80 at risk EG00123 events15 affected79 at risk
Anal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0006 events5 affected80 at risk EG0010 events0 affected79 at risk
Ascites	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Bloating	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0018 events4 affected79 at risk
Colitis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Colonic hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Constipation	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00078 events38 affected80 at risk EG00165 events34 affected79 at risk
Dental caries	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00060 events34 affected80 at risk EG00148 events33 affected79 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0006 events5 affected80 at risk EG0019 events7 affected79 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0008 events7 affected80 at risk EG0018 events4 affected79 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0008 events7 affected80 at risk EG0011 events1 affected79 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Esophagitis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Fecal incontinence	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Flatulence	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0011 events1 affected79 at risk
Gastric hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00018 events7 affected80 at risk EG0016 events5 affected79 at risk
Gastrointestinal disorders - Other	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected80 at risk EG00110 events7 affected79 at risk
Gingival pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0015 events2 affected79 at risk
Hemorrhoidal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0007 events6 affected80 at risk EG0017 events7 affected79 at risk
Ileus	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected79 at risk
Lower gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Mucositis oral	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00019 events14 affected80 at risk EG00116 events13 affected79 at risk
Nausea	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00067 events34 affected80 at risk EG00195 events34 affected79 at risk
Oral hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected79 at risk
Oral pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00011 events8 affected80 at risk EG0014 events4 affected79 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Peritoneal necrosis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Rectal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Rectal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Stomach pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Typhlitis	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Upper gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG00017 events13 affected80 at risk EG00136 events20 affected79 at risk
Chills	General disorders	MedDRA 12	Systematic Assessment	EG00019 events9 affected80 at risk EG00121 events16 affected79 at risk
Edema face	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0014 events4 affected79 at risk
Edema limbs	General disorders	MedDRA 12	Systematic Assessment	EG00058 events32 affected80 at risk EG00151 events25 affected79 at risk
Edema trunk	General disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Facial pain	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0014 events2 affected79 at risk
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG000173 events53 affected80 at risk EG001170 events51 affected79 at risk
Fever	General disorders	MedDRA 12	Systematic Assessment	EG00016 events15 affected80 at risk EG00110 events8 affected79 at risk
Flu like symptoms	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0015 events2 affected79 at risk
Gait disturbance	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
General disorders and administration site conditions - Other	General disorders	MedDRA 12	Systematic Assessment	EG0009 events8 affected80 at risk EG00110 events8 affected79 at risk
Infusion related reaction	General disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0010 events0 affected79 at risk
Infusion site extravasation	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Injection site reaction	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events1 affected79 at risk
Localized edema	General disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0012 events2 affected79 at risk
Malaise	General disorders	MedDRA 12	Systematic Assessment	EG0006 events5 affected80 at risk EG0014 events3 affected79 at risk
Non-cardiac chest pain	General disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0018 events7 affected79 at risk
Pain	General disorders	MedDRA 12	Systematic Assessment	EG00023 events10 affected80 at risk EG00114 events10 affected79 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hepatobiliary disorders - Other	Hepatobiliary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Allergic reaction	Immune system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events1 affected79 at risk
Anaphylaxis	Immune system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Bronchial infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Catheter related infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected79 at risk
Conjunctivitis infective	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0013 events3 affected79 at risk
Gallbladder infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Gum infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Hepatitis viral	Infections and infestations	MedDRA 12	Systematic Assessment	EG0005 events1 affected80 at risk EG0010 events0 affected79 at risk
Infections and infestations - Other	Infections and infestations	MedDRA 12	Systematic Assessment	EG0007 events7 affected80 at risk EG00114 events11 affected79 at risk
Joint infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Lip infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Lung infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG00023 events14 affected80 at risk EG00114 events12 affected79 at risk
Mucosal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0011 events1 affected79 at risk
Nail infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Otitis externa	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Paronychia	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events1 affected79 at risk
Pharyngitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Phlebitis infective	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events1 affected79 at risk
Salivary gland infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Sepsis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0014 events3 affected79 at risk
Sinusitis	Infections and infestations	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0016 events3 affected79 at risk
Skin infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG00011 events9 affected80 at risk EG00117 events10 affected79 at risk
Small intestine infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Tooth infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Upper respiratory infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0006 events6 affected80 at risk EG0012 events1 affected79 at risk
Urinary tract infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0007 events7 affected80 at risk EG00110 events8 affected79 at risk
Wound infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0005 events3 affected80 at risk EG0011 events1 affected79 at risk
Bruising	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG00023 events12 affected80 at risk EG0015 events4 affected79 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0005 events3 affected80 at risk EG00112 events10 affected79 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Injury, poisoning and procedural complications - Other	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0006 events5 affected80 at risk EG0013 events3 affected79 at risk
Vascular access complication	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events1 affected79 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA 12	Systematic Assessment	EG0007 events5 affected80 at risk EG00117 events9 affected79 at risk
Alanine aminotransferase increased	Investigations	MedDRA 12	Systematic Assessment	EG00038 events22 affected80 at risk EG00144 events19 affected79 at risk
Alkaline phosphatase increased	Investigations	MedDRA 12	Systematic Assessment	EG00034 events17 affected80 at risk EG00129 events15 affected79 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 12	Systematic Assessment	EG00040 events28 affected80 at risk EG00154 events27 affected79 at risk
Blood bilirubin increased	Investigations	MedDRA 12	Systematic Assessment	EG00044 events20 affected80 at risk EG00116 events12 affected79 at risk
Blood prolactin abnormal	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Cardiac troponin I increased	Investigations	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events2 affected79 at risk
Cholesterol high	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Creatinine increased	Investigations	MedDRA 12	Systematic Assessment	EG00026 events15 affected80 at risk EG00162 events20 affected79 at risk
Ejection fraction decreased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events1 affected79 at risk
Electrocardiogram QT corrected interval prolonged	Investigations	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0018 events5 affected79 at risk
GGT increased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Haptoglobin decreased	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Hemoglobin increased	Investigations	MedDRA 12	Systematic Assessment	EG0007 events2 affected80 at risk EG0012 events2 affected79 at risk
INR increased	Investigations	MedDRA 12	Systematic Assessment	EG00025 events10 affected80 at risk EG00123 events13 affected79 at risk
Investigations - Other	Investigations	MedDRA 12	Systematic Assessment	EG00020 events5 affected80 at risk EG00126 events5 affected79 at risk
Lymphocyte count decreased	Investigations	MedDRA 12	Systematic Assessment	EG00045 events19 affected80 at risk EG00154 events18 affected79 at risk
Lymphocyte count increased	Investigations	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Neutrophil count decreased	Investigations	MedDRA 12	Systematic Assessment	EG000266 events62 affected80 at risk EG001224 events56 affected79 at risk
Platelet count decreased	Investigations	MedDRA 12	Systematic Assessment	EG000233 events62 affected80 at risk EG001236 events59 affected79 at risk
Weight gain	Investigations	MedDRA 12	Systematic Assessment	EG0007 events4 affected80 at risk EG0014 events3 affected79 at risk
Weight loss	Investigations	MedDRA 12	Systematic Assessment	EG00031 events14 affected80 at risk EG00136 events12 affected79 at risk
White blood cell decreased	Investigations	MedDRA 12	Systematic Assessment	EG000125 events30 affected80 at risk EG00198 events29 affected79 at risk
Acidosis	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0010 events0 affected79 at risk
Alkalosis	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00056 events32 affected80 at risk EG00178 events30 affected79 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0006 events3 affected80 at risk EG00111 events4 affected79 at risk
Hypercalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0012 events2 affected79 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG000114 events40 affected80 at risk EG001122 events38 affected79 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG00110 events7 affected79 at risk
Hypermagnesemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0015 events3 affected79 at risk
Hypernatremia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0007 events4 affected80 at risk EG0012 events1 affected79 at risk
Hypertriglyceridemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hyperuricemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0006 events3 affected80 at risk EG0012 events2 affected79 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00089 events33 affected80 at risk EG00194 events37 affected79 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00056 events27 affected80 at risk EG00166 events25 affected79 at risk
Hypoglycemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG00115 events5 affected79 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00040 events25 affected80 at risk EG00146 events26 affected79 at risk
Hypomagnesemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00033 events14 affected80 at risk EG00119 events13 affected79 at risk
Hyponatremia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00063 events24 affected80 at risk EG00148 events26 affected79 at risk
Hypophosphatemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG00016 events14 affected80 at risk EG00114 events11 affected79 at risk
Metabolism and nutrition disorders - Other	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0007 events3 affected80 at risk EG00119 events4 affected79 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00026 events13 affected80 at risk EG00125 events4 affected79 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0008 events4 affected80 at risk EG00111 events4 affected79 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00018 events12 affected80 at risk EG00126 events16 affected79 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0005 events3 affected80 at risk EG0018 events8 affected79 at risk
Chest wall pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events3 affected79 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected80 at risk EG0012 events2 affected79 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00039 events22 affected80 at risk EG00140 events14 affected79 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Muscle weakness left-sided	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0012 events2 affected79 at risk
Muscle weakness upper limb	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0015 events1 affected79 at risk
Musculoskeletal and connective tissue disorder - Other	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00018 events8 affected80 at risk EG0017 events5 affected79 at risk
Musculoskeletal deformity	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0009 events7 affected80 at risk EG00124 events7 affected79 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0013 events2 affected79 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG00018 events10 affected80 at risk EG00117 events9 affected79 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0011 events1 affected79 at risk
Treatment related secondary malignancy	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Acoustic nerve disorder NOS	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Arachnoiditis	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Cognitive disturbance	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0005 events1 affected80 at risk EG0013 events2 affected79 at risk
Dizziness	Nervous system disorders	MedDRA 12	Systematic Assessment	EG00022 events13 affected80 at risk EG00137 events22 affected79 at risk
Dysgeusia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0007 events3 affected80 at risk EG00113 events6 affected79 at risk
Headache	Nervous system disorders	MedDRA 12	Systematic Assessment	EG00022 events15 affected80 at risk EG00130 events22 affected79 at risk
Intracranial hemorrhage	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Lethargy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0012 events2 affected79 at risk
Nervous system disorders - Other	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0008 events5 affected80 at risk EG0019 events4 affected79 at risk
Neuralgia	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0018 events2 affected79 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0019 events3 affected79 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG00160 events19 affected79 at risk
Presyncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG00110 events6 affected79 at risk
Seizure	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Sinus pain	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0011 events1 affected79 at risk
Somnolence	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Stroke	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Syncope	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0017 events4 affected79 at risk
Tremor	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0013 events2 affected79 at risk
Agitation	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0012 events1 affected79 at risk
Anxiety	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00024 events9 affected80 at risk EG00115 events9 affected79 at risk
Confusion	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00010 events8 affected80 at risk EG0018 events7 affected79 at risk
Delirium	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Depression	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00023 events13 affected80 at risk EG00124 events9 affected79 at risk
Hallucinations	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Insomnia	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG00032 events15 affected80 at risk EG00123 events12 affected79 at risk
Psychiatric disorders - Other	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0013 events2 affected79 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG00014 events6 affected80 at risk EG00128 events5 affected79 at risk
Cystitis noninfective	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Hematuria	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0006 events5 affected80 at risk EG0019 events6 affected79 at risk
Hemoglobinuria	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0010 events0 affected79 at risk
Proteinuria	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0018 events6 affected79 at risk
Renal and urinary disorders - Other	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0006 events4 affected80 at risk EG0013 events2 affected79 at risk
Renal calculi	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0004 events1 affected80 at risk EG0011 events1 affected79 at risk
Urinary frequency	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0013 events3 affected79 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected80 at risk EG0013 events3 affected79 at risk
Urinary retention	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0004 events3 affected80 at risk EG0015 events4 affected79 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Urinary tract pain	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events3 affected79 at risk
Urinary urgency	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0010 events0 affected79 at risk
Breast pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected80 at risk EG0010 events0 affected79 at risk
Genital edema	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Penile pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Perineal pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Reproductive system and breast disorders - Other	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0014 events3 affected79 at risk
Scrotal pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Vaginal pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0007 events5 affected80 at risk EG0011 events1 affected79 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0012 events2 affected79 at risk
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0006 events5 affected80 at risk EG0010 events0 affected79 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00045 events28 affected80 at risk EG00136 events16 affected79 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00075 events40 affected80 at risk EG00163 events33 affected79 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0008 events7 affected80 at risk EG00110 events8 affected79 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hoarseness	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0012 events2 affected79 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0014 events4 affected79 at risk
Laryngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Laryngeal mucositis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Mediastinal hemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0008 events7 affected80 at risk EG00110 events5 affected79 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0008 events6 affected80 at risk EG0018 events6 affected79 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Postnasal drip	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0006 events6 affected80 at risk EG0012 events2 affected79 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0012 events2 affected79 at risk
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0018 events6 affected79 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Respiratory, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00021 events10 affected80 at risk EG00110 events8 affected79 at risk
Sinus disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Sleep apnea	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00010 events8 affected80 at risk EG00111 events8 affected79 at risk
Tracheal mucositis	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0012 events2 affected79 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0006 events2 affected80 at risk EG0015 events3 affected79 at risk
Bullous dermatitis	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0013 events2 affected79 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0013 events3 affected79 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0006 events5 affected80 at risk EG0012 events2 affected79 at risk
Erythroderma	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Nail loss	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0003 events2 affected80 at risk EG0010 events0 affected79 at risk
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Periorbital edema	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0012 events2 affected79 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0004 events4 affected80 at risk EG0019 events5 affected79 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0007 events6 affected80 at risk EG0019 events6 affected79 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG00035 events25 affected80 at risk EG00132 events21 affected79 at risk
Scalp pain	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected80 at risk EG0011 events1 affected79 at risk
Skin and subcutaneous tissue disorders - Other	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG00029 events16 affected80 at risk EG00125 events16 affected79 at risk
Skin induration	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0003 events1 affected80 at risk EG0011 events1 affected79 at risk
Skin ulceration	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0011 events1 affected79 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0015 events1 affected79 at risk
Surgical and medical procedures - Other	Surgical and medical procedures	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Flushing	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk
Hematoma	Vascular disorders	MedDRA 12	Systematic Assessment	EG0005 events4 affected80 at risk EG0012 events2 affected79 at risk
Hypertension	Vascular disorders	MedDRA 12	Systematic Assessment	EG00021 events11 affected80 at risk EG00117 events12 affected79 at risk
Hypotension	Vascular disorders	MedDRA 12	Systematic Assessment	EG00020 events16 affected80 at risk EG00141 events26 affected79 at risk
Phlebitis	Vascular disorders	MedDRA 12	Systematic Assessment	EG0003 events3 affected80 at risk EG0010 events0 affected79 at risk
Superficial thrombophlebitis	Vascular disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected80 at risk EG0011 events1 affected79 at risk
Thromboembolic event	Vascular disorders	MedDRA 12	Systematic Assessment	EG0005 events5 affected80 at risk EG0014 events3 affected79 at risk
Vascular disorders - Other	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected80 at risk EG0010 events0 affected79 at risk

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Term
D001897	Boronic Acids
D000148	Acids, Noncarboxylic
D000143	Acids
D007287	Inorganic Chemicals
D001896	Boron Compounds
D009930	Organic Chemicals
D011719	Pyrazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001374	Azacitidine
D001372	Aza Compounds
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012263	Ribonucleosides
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics

ID	Title	Description
BG000	Arm I (Decitabine)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
BG001	Arm II (Decitabine and Bortezomib)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm I (Decitabine)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-10. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	70	82	43	80	66	80
EG001	Arm II (Decitabine and Bortezomib)	REMISSION INDUCTION THERAPY: Patients receive 20 mg/m^2 decitabine IV over 1 hour QD on days 2-11 and 1.3 mg/m^2 bortezomib SC on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving CR or CRi proceed to continuation therapy. Patients achieving CR or CRi proceed to maintenance therapy. CONTINUATION THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive 1.3 mg/m^2 bortezomib SC on day 1 and 20 mg/m^2 decitabine IV over 1 hour QD on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	75	83	45	79	61	79