Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bo... | NCT01818752

ID	Type	Description	Link
2012-005283-97	EudraCT Number
20130397	Other Identifier	Amgen Inc.

Label	Type	Description	Intervention Names
Carfilzomib, Melphalan, Prednisone	Experimental	Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Drug: Carfilzomib Drug: Melphalan Drug: Prednisone
Bortezomib, Melphalan, Prednisone	Active Comparator	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².	Drug: Bortezomib Drug: Melphalan Drug: Prednisone

Name	Type	Description	Arm Group Labels	Other Names
Carfilzomib	Drug	Carfilzomib was administered over 30 minutes on days 1, 2, 8, 9, 22, 23, 29, and 30 for nine 42-day cycles. Carfilzomib 20 mg/m² IV was administered on days 1 and 2 of cycle 1, followed by escalation to 36 mg/m² IV starting on day 8 of cycle 1.

Measure	Description	Time Frame
Progression-Free Survival (PFS)	Progression-free survival was defined as the time from randomization to the earlier of documented disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier methods. The duration of PFS was censored for participants with no baseline and/or post-baseline disease assessments, who started a new anti-cancer therapy before documentation of disease progression or death, death or disease progression after missed disease assessment of 100 consecutive days or longer, or who were alive without documentation of disease progression before the data cutoff date, including lost to follow-up prior to disease progression. Participants were evaluated for disease response and progression according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC), determined centrally using a validated computer algorithm in a blinded manner.	From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.

Measure	Description	Time Frame
Overall Survival (OS)	Overall survival (OS) was defined as the time from randomization to the date of death (whatever the cause). Participants who were alive or lost to follow-up as of the data analysis cut-off date were censored on the date the patient was last known to be alive. Median overall survival was estimated using the Kaplan-Meier method.	From randomization until the data cut-off date of 15 July 2016; median follow-up time for OS was 22.2 and 22.5 months in the bortezomib and carfilzomib arms respectively.

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
California Cancer Associates for Research & Excellence, Inc. (cCARE)		Fresno	California	93720	United States

PubMed Identifier	Type	Citation	Retractions
29991494	Background	Chari A, Stewart AK, Russell SD, Moreau P, Herrmann J, Banchs J, Hajek R, Groarke J, Lyon AR, Batty GN, Ro S, Huang M, Iskander KS, Lenihan D. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood Adv. 2018 Jul 10;2(13):1633-1644. doi: 10.1182/bloodadvances.2017015545.
30819926

Label	URL
AmgenTrials clinical trials website	View source

ID	Title	Description
FG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Type

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Description

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Reporting Status

Anticipated Posting Date

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Dispersion Type

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Calculate Percentage

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Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

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Analyses

Primary

Progression-Free Survival (PFS)

Progression-free survival was defined as the time from randomization to the earlier of documented disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier methods. The duration of PFS was censored for participants with no baseline and/or post-baseline disease assessments, who started a new anti-cancer therapy before documentation of disease progression or death, death or disease progression after missed disease assessment of 100 consecutive days or longer, or who were alive without documentation of disease progression before the data cutoff date, including lost to follow-up prior to disease progression.

Participants were evaluated for disease response and progression according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC), determined centrally using a validated computer algorithm in a blinded manner.

The intent-to-treat population included all randomized participants.

Posted

Median

95% Confidence Interval

months

From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.

ID	Title	Description
OG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
OG001	Carfilzomib, Melphalan, Prednisone	Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Units	Counts
Participants	OG000477 OG001478

Title

Denominators

Categories

Title	Measurements
	OG00022.1(20.8 to 24.4) OG00122.3(20.9 to 26.7)

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	The inferential test associated with the primary analysis of PFS was assessed against an overall 1-sided significance level of α=0.025.	Log Rank	Log-rank p-value (1-sided) stratified by ISS stage, choice of route of bortezomib administration, region and age.	0.1590	The p-value boundary for PFS analysis was 0.02141.	Hazard Ratio (HR)	0.906			2-Sided	95	0.746	1.101			The hazard ratio (Carfilzomib/Bortezomib) was estimated using a Cox proportional hazards model stratified by ISS stage, choice of route of bortezomib administration, region and age.

Secondary

Overall Survival (OS)

Overall survival (OS) was defined as the time from randomization to the date of death (whatever the cause). Participants who were alive or lost to follow-up as of the data analysis cut-off date were censored on the date the patient was last known to be alive.

Median overall survival was estimated using the Kaplan-Meier method.

Intent-to-treat population

Posted

Median

95% Confidence Interval

months

From randomization until the data cut-off date of 15 July 2016; median follow-up time for OS was 22.2 and 22.5 months in the bortezomib and carfilzomib arms respectively.

ID	Title	Description
OG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
OG001	Carfilzomib, Melphalan, Prednisone	Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Secondary

Overall Response Rate

Disease response was evaluated according to the IMWG-URC using a validated computer algorithm. Overall response was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).

sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).

CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM biopsy; VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.

PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.

Intent-to-treat population

Posted

Number

95% Confidence Interval

percentage of participants

Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.

ID	Title	Description
OG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Secondary

Complete Response Rate

Complete response rate was defined as the percentage of participants in each treatment group who achieved a sCR or CR per the IMWG-URC as their best response.

sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).

CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM biopsy.

Intent-to-treat population

Posted

Number

95% Confidence Interval

percentage of participants

ID	Title	Description
OG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
OG001	Carfilzomib, Melphalan, Prednisone	Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Secondary

Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy

Neuropathy events were defined as Grade 2 or higher peripheral neuropathy as specified by peripheral neuropathy Standardised Medical Dictionary for Regulatory Activities (MedDRA) Query, narrow (scope) (SMQN) terms.

Peripheral neuropathy was assessed by neurologic exam and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03:

Grade 1: Asymptomatic; Grade 2: Moderate symptoms, limiting instrumental activities of daily living (ADL) Grade 3: Severe symptoms; limiting self-care ADL; Grade 4: Life-threatening consequences, urgent intervention indicated; Grade 5: Death.

The safety population included all randomized participants who received at least 1 dose of any study treatment (i.e., carfilzomib, bortezomib, melphalan, or prednisone).

Posted

Number

95% Confidence Interval

percentage of participants

From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.

ID	Title	Description
OG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Secondary

European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores

The EORTC QLQ-C30 is a validated self-rating questionnaire including 30 items used to assess the overall quality of life in cancer patients.

It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).

The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with higher scores indicating better Global Health Status/QOL.

Intent-to treat population with available data at each time point.

Posted

Mean

Standard Deviation

units on a scale

Baseline, weeks 6, 12, 18, 24, 30, 36, 42 and 48

ID	Title	Description
OG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
OG001	Carfilzomib, Melphalan, Prednisone	Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Secondary

Number of Participants With Adverse Events

Adverse events (AEs)were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, where GRADE 1 = Mild; GRADE 2 = Moderate; GRADE 3 = Severe; GRADE 4 = Life-threatening; GRADE 5 = Fatal.

A serious adverse event is an adverse event that met 1 or more of the following criteria:

Death
Life-threatening
Required inpatient hospitalization or prolongation of an existing hospitalization
Resulted in persistent or significant disability/incapacity
Congenital anomaly/birth defect
Important medical event that jeopardized the participant and may have required medical or surgical intervention to prevent 1 of the outcomes listed above.

Treatment-related adverse events are adverse events considered related to at least 1 investigational product by the investigator, including those with unknown relationship.

Safety population

Posted

Number

participants

ID	Title	Description
OG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0006 affected470 at risk EG00111 affected474 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0005 affected470 at risk EG0014 affected474 at risk
Haemolytic uraemic syndrome	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected470 at risk EG0014 affected474 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG00011 affected470 at risk EG0015 affected474 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Acute left ventricular failure	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0014 affected474 at risk
Angina pectoris	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Arrhythmia	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected470 at risk EG0017 affected474 at risk
Atrial flutter	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0012 affected474 at risk
Atrial tachycardia	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Atrioventricular block	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Cardiac amyloidosis	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Cardiac arrest	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Cardiac failure	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0007 affected470 at risk EG00121 affected474 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0018 affected474 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Coronary artery disease	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Coronary artery occlusion	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hypertensive cardiomegaly	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Left ventricular failure	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Myocardial infarction	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0013 affected474 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Tachycardia	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Diplopia	Eye disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Retinopathy	Eye disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Colitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0007 affected470 at risk EG0013 affected474 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Faecaloma	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Gastritis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Ileus	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0005 affected470 at risk EG0010 affected474 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Intestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0010 affected474 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Melaena	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0012 affected474 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Subileus	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0006 affected470 at risk EG0013 affected474 at risk
Adverse drug reaction	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Asthenia	General disorders	MedDRA 19.0	Systematic Assessment	EG0006 affected470 at risk EG0014 affected474 at risk
Chest pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0012 affected474 at risk
Death	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Disease progression	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Fatigue	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
General physical health deterioration	General disorders	MedDRA 19.0	Systematic Assessment	EG0005 affected470 at risk EG0012 affected474 at risk
Generalised oedema	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Infusion site extravasation	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Infusion site pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Malaise	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Mucosal inflammation	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Non-cardiac chest pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Oedema peripheral	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Peripheral swelling	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0009 affected470 at risk EG00116 affected474 at risk
Sudden death	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0012 affected474 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hepatitis toxic	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Hepatocellular injury	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Hypersensitivity	Immune system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Abdominal infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Abscess limb	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Bacteraemia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Bacterial infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0012 affected474 at risk
Bronchitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0018 affected474 at risk
Cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Clostridium colitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Device related infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Ear infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Erysipelas	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Escherichia infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Gastroenteritis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Gastroenteritis norovirus	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Hepatitis C	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hepatitis viral	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0013 affected474 at risk
Influenza	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Legionella infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Lung infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0006 affected470 at risk EG0015 affected474 at risk
Otitis media	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00031 affected470 at risk EG00146 affected474 at risk
Postoperative wound infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pseudomonas bronchitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pyelonephritis chronic	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0012 affected474 at risk
Respiratory tract infection bacterial	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Rhinovirus infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Sepsis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0007 affected470 at risk EG0018 affected474 at risk
Sepsis syndrome	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Septic shock	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0012 affected474 at risk
Sinusitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Tonsillitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Tooth infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0004 affected470 at risk EG0013 affected474 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0015 affected474 at risk
Urosepsis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0012 affected474 at risk
Viral infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0014 affected474 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0012 affected474 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Heat illness	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0004 affected470 at risk EG0011 affected474 at risk
Pneumoconiosis	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Spinal cord injury cervical	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Blood creatinine increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0012 affected474 at risk
Blood uric acid increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
C-reactive protein increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Creatinine renal clearance decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Haemoglobin decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Platelet count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0012 affected474 at risk
Urine output decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Acidosis	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0005 affected470 at risk EG0011 affected474 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0012 affected474 at risk
Hyperproteinaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Tetany	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0013 affected474 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected470 at risk EG0016 affected474 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0013 affected474 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Polyarthritis	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0011 affected474 at risk
Adenocarcinoma gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Breast cancer stage I	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Oesophageal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Paraneoplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Amnesia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Aphasia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Autonomic nervous system imbalance	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Autonomic neuropathy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Brain oedema	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Cauda equina syndrome	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Cerebral infarction	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0012 affected474 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0011 affected474 at risk
Coma	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Dementia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Encephalopathy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Facial paresis	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Hypotonia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Lacunar infarction	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Loss of consciousness	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Memory impairment	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Myoclonus	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Neuralgia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0010 affected474 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Polyneuropathy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Presyncope	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Seizure	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Somnolence	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Spinal cord compression	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Syncope	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0005 affected470 at risk EG0014 affected474 at risk
Toxic encephalopathy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Trigeminal neuralgia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
VIth nerve paralysis	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Confusional state	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0013 affected474 at risk
Hallucination	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Illusion	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Psychiatric decompensation	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG00010 affected470 at risk EG00119 affected474 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0013 affected474 at risk
Prerenal failure	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Renal failure	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG00114 affected474 at risk
Renal impairment	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Renal injury	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Urinary retention	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0013 affected474 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Prostatomegaly	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0019 affected474 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Mediastinal haematoma	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0012 affected474 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0017 affected474 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected470 at risk EG0016 affected474 at risk
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Upper respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected470 at risk EG0010 affected474 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0011 affected474 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Immobile	Social circumstances	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Aortic aneurysm repair	Surgical and medical procedures	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Bone operation	Surgical and medical procedures	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Vertebroplasty	Surgical and medical procedures	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Aortic dissection	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Circulatory collapse	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Haematoma	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Hypertension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0018 affected474 at risk
Hypertensive crisis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0012 affected474 at risk
Hypotension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0007 affected470 at risk EG0013 affected474 at risk
Hypovolaemic shock	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected470 at risk EG0010 affected474 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected470 at risk EG0010 affected474 at risk
Peripheral artery occlusion	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Peripheral artery stenosis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Phlebitis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected470 at risk EG0011 affected474 at risk

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System 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
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D010649	Phenylalanine
D024322	Amino Acids, Aromatic
D000598	Amino Acids, Cyclic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
BG001	Carfilzomib, Melphalan, Prednisone	Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
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	Bortezomib, Melphalan, Prednisone	Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².			198	470	437	470
EG001	Carfilzomib, Melphalan, Prednisone	Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².			235	474	437	474

ID	Term
C524865	carfilzomib
D000069286	Bortezomib
D008558	Melphalan
D011241	Prednisone