Study of Immunotherapy to Treat Advanced Prostate Cancer | NCT00861614

NCT00861614

ID	Type	Description	Link
2008-003314-97

Status Module

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Ipilimumab	Active Comparator		Drug: Ipilimumab
Placebo	Placebo Comparator		Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ipilimumab	Drug	5 mg/ml solution, Intravenous, 10 mg/kg, Every 3 weeks for up to 4 doses in the Induction Phase. Every 12 weeks in the Maintenance Phase, Up to 24 weeks in Induction, 48+ weeks in the Maintenance Phase, or until Treatment Stopping Criteria are met, withdrawal of consent, lost to follow-up, death, study closure

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS is defined as the time in months from randomization date to date of death due to any cause in all randomized subjects. For participants alive at the time of the database cutoff date, OS was censored at the last date the participant was known to be alive.	Date of randomization to date of death
Overall Survival Rate	The overall survival (OS) rate is a percentage, representing the fraction of all randomized participants who were alive following treatment, from 1 to 5 years. OS was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.	Date of randomization to date of death

Secondary Outcomes

Measure	Description	Time Frame
Progression Free Survival (PFS)	All PFS events were based on investigator's assessment. Participants who were alive and did not experience a PFS event were censored at the earlier of the latest prostate-specific antigen (PSA) or radiological tumor assessment date. Participants who did not die, showed no clinical deterioration, and who had no recorded post-baseline PSA or radiological tumor assessment were censored at randomization date.

Eligibility Module

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Southern Cancer Center		Mobile	Alabama	36608	United States
Alaska Clinical Research Center, Llc

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25907621	Derived	Trump D. Commentary on: "Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): A multicentre, randomised, double-blind, phase 3 trial." Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengelov L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR, CA184-043 Investigators. Departments of Urology and Immunology and Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA, Electronic address: kwon.eugene@mayo.edu; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and Brady Urological Institute, Baltimore, MD, USA; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA; Institut Gustave Roussy, University of Paris-Sud, Villejuif, France; Institut Gustave Roussy, Villejuif, France; VU University Medical Centre, Amsterdam, Netherlands; Vienna General Hospital, Medical University Vienna, Vienna, Austria; Institut Bergonie, Bordeaux, France; CHU Caremeau, Nimes, France; Centro Medico Austral, Buenos Aires, Argentina; Centre Jean Perrin, Clermont-Ferrand, France; St John of God Hospital, Subiaco, WA, Australia; University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy; Hospital de Caridade de Ijui, Ijui, Brazil; Nottingham University Hospital, Nottingham, UK; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; Netherlands Cancer Institute and Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; Institute of Oncology Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania; Hospital Britanico de Buenos Aires, Buenos Aires, Argentina; Herlev Hospital, Herlev, Denmark; Odense University Hospital, Odense, Denmark; University of Texas MD Anderson Cancer Center, Houston, Urol Oncol. 2016 May;34(5):249-50. doi: 10.1016/j.urolonc.2015.03.013. Epub 2015 Apr 20.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gray units (Gy) to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4,7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
BG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed PD, drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
BG002	Total	Total of all reporting groups

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)

OS is defined as the time in months from randomization date to date of death due to any cause in all randomized subjects. For participants alive at the time of the database cutoff date, OS was censored at the last date the participant was known to be alive.

All randomized participants

Posted

Median

95% Confidence Interval

months

Date of randomization to date of death

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Units	Counts
Participants	OG000399 OG001400

Title

Denominators

Categories

Title	Measurements
	OG00011.04(9.46 to 12.48) OG00110.02(8.38 to 11.17)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.0127		Hazard Ratio (HR)	0.83			2-Sided	95	0.71	0.96			Ipilimumab over placebo	No	Superiority or Other

Primary

Overall Survival Rate

The overall survival (OS) rate is a percentage, representing the fraction of all randomized participants who were alive following treatment, from 1 to 5 years. OS was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.

All randomized participants

Posted

Number

95% Confidence Interval

percentage of participants

Date of randomization to date of death

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Progression Free Survival (PFS)

All PFS events were based on investigator's assessment. Participants who were alive and did not experience a PFS event were censored at the earlier of the latest prostate-specific antigen (PSA) or radiological tumor assessment date. Participants who did not die, showed no clinical deterioration, and who had no recorded post-baseline PSA or radiological tumor assessment were censored at randomization date.

All randomized participants

Posted

Median

95% Confidence Interval

months

Date of randomization to earliest date of confirmed PSA or radiological progression, clinical deterioration or death

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Pain Response

The percentage of participants with a pain response assessed using the Brief Pain Inventory Short Form (BPI-SF) completed by participants throughout the study in a daily diary log. Pain-evaluable participants were defined as those with a decrease in the average daily worst pain intensity by at least 30% from baseline, maintained over 2 consecutive evaluations without the use of any rescue analgesic medication or increase in analgesic use in the same time period.

All pain-evaluable participants

Posted

Number

95% Confidence Interval

percentage of participants

Assessed at screening, weeks 12, 18, 24, and at the end of treatment visit

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Duration of Pain Response

The time between the initial date of pain response and completion date of pain response. The initial date when the pain response criterion was achieved was considered the pain response date. The earlier of date of death, date of tumor resection surgery, or date when pain response criterion was no longer met was considered the completion date of the pain response. If none of these scenarios occurred, the completion of the pain response was set to the last known alive date.

All pain-evaluable participants with pain response

Posted

Median

95% Confidence Interval

months

Day of initial pain response to day of completion of pain response or date of death

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR)

AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.

SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during study and up to 70 days after last dose. IrAEs=AEs potentially associated with inflammation and considered to be causally related to study drug and grouped into gastrointestinal (GI), hepatic, skin, endocrine and neurological. ImARs were collected prospectively and grouped into enterocolitis, hepatitis, dermatitis, neuropathies and endocrinopathies. IrAEs/ imARs were graded using Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Ver. 3.0.

All treated participants

Posted

Number

participants

Randomization to date of death

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE)

The time between first dose of study drug and date of earliest Grade 3 or 4 irAE. These irAEs are AEs of unknown etiology, consistent with an immune phenomenon and considered as causally related to drug exposure. The five subcategories of irAE examined include gastrointestinal (GI), liver, skin, endocrine, and neurological and are graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.

All treated participants

Posted

Median

95% Confidence Interval

weeks

Day 1 to 70 days after last dose of study drug

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE)

Time between the date of onset of a Grade 3 or 4 irAE and the date of improvement to Grade 1 or less or the worst grade at baseline.

All treated participants

Posted

Median

95% Confidence Interval

weeks

Day 1 to 70 days after last dose of study drug

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR)

The time between first dose of study drug and date of earliest Grade 3 or 4 imAR. ImARs were collected prospectively and grouped into enterocolitis, hepatitis, dermatitis, neuropathies and endocrinopathies and graded using Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Ver. 3.0.

Only the Ipilimumab + Radiotherapy group of participants was included in the analysis because ipilimumab is associated with inflammatory events resulting from increased or excessive immune activity likely to be related to its mechanism of action.

All treated participants receiving Ipilimumab + Radiotherapy

Posted

Median

Full Range

weeks

Day 1 to time of onset of the imAR of interest

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Units	Counts

Secondary

Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0

Time between the date of onset of an imAR to the date of resolution date of the event or the last known date participant was alive if an event did not resolve.

All treated participants receiving Ipilimumab + Radiotherapy

Posted

Median

Full Range

weeks

Day 1 to 70 days after last dose of study drug

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Units	Counts
Participants

Secondary

Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline

Comparison of baseline versus worst grade hematology laboratory tests as measured by white blood count (WBC), absolute neutrophil count (ANC), platelet count, hemoglobin and lymphocyte results. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for WBC were based on Gr 1: 3.0 - < Lower Limit of Normal (LLN); Gr 2: 2.0 - < 3.0; Gr 3: 1.0 - < 2.0; Gr4: < 1.0. Abnormal values for Hemoglobin were based on Gr 1: 10.0 - < LLN; Gr 2: 8.0 - < 10.0; Gr 3: 6.5 - < 8.0; Gr 4: < 6.5. Abnormal values for Lymphocytes were based on Gr 1: 0.8 - < 1.5; Gr 2: 0.5 - < 0.8; Gr 3): 0.2 - < 0.5; Gr 4: < 0.2. Abnormal values for ANC were based on Gr 1: 1.5 - < 2.0; Gr 2: 1.0 - < 1.5; Gr 3: 0.5 - < 1.0; Gr 4: < 0.5. Abnormal values for Platelets were based on Gr 1: 75.0 - < LLN; Gr 2: 50.0 - < 75.0; Gr 3: 25.0 - < 50.0; Gr 4: < 25.0.

All treated participants

Posted

Number

participants

Day 1 to 70 days after last dose of study drug

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline

Comparison of baseline versus worst grade liver function as measured by alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and alkaline phosphatase (ALP). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for ALP, ALT and AST were based on grades; Gr 1: > 1.0 - 2.5 * upper limits of normal (ULN); Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Abnormal values for Total Bilirubin were based on Gr 1: > 1.0 - 1.5 * upper limits of normal (ULN); Gr 2: > 1.5 - 3.0 * ULN; Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN.

All treated participants

Posted

Number

participants

Day 1 to 70 days after last dose of study drug

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy

Secondary

Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline

Comparison of baseline versus worst grade serum chemistry as measured by lipase and amylase analysis. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for lipase: Gr1: > 1.0 - 1.5 * ULN; Gr2: > 1.5 - 2.0 * ULN; Gr 3: > 2.0 - 5.0 * ULN; Gr4: > 5.0*ULN. Abnormal values for amylase: Gr1: > 1.0 - 1.5 * ULN; Gr 2: > 1.5 - 2.0 * ULN; Gr 3: > 2.0 - 5.0 * ULN; Gr4: > 5.0 * ULN.

All treated participants

Posted

Number

participants

Day 1 to 70 days after last dose of study drug

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Secondary

Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline

Comparison of baseline versus worst grade renal function as measured by creatinine analysis. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr).Gr 0: within normal range. Abnormal values for Creatinine were based on Gr 1: > 1.0 - 1.5*ULN; Gr 2: > 1.5 - 3.0*ULN; Gr 3: > 3.0 - 6.0*ULN; Gr 4: > 6.0*ULN.

All treated participants

Posted

Number

participants

Day 1 to 70 days after last dose of study drug

ID	Title	Description
OG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.
OG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ipilimumab + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, 10 milligrams (mg) of ipilimumab per kilogram (kg) of body weight was administered intravenously (IV) over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.			257	393	350	393
EG001	Placebo + Radiotherapy	Prior to receiving study drug, participants receive radiotherapy at 8 Gy to at least 1 and up to a maximum of 5, bone fields, all in one day. Within 2 days of radiotherapy, placebo solution (0.9% sodium chloride or 5% dextrose) infused IV over 90 minutes. During the treatment phase, dosing was at weeks 1, 4, 7 and 10. In the maintenance phase, dosing was a 12-week intervals, beginning at week 24. Dosing continued until confirmed progressive disease (PD), drug intolerance, clinical deterioration, death, withdrawal of consent or subject lost to follow-up.			164	396	333	396

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute prerenal failure	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Adrenocorticotropic hormone deficiency	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Cellulitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0012 affected396 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00018 affected393 at risk EG00110 affected396 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Device malfunction	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Epstein-Barr virus infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
General physical health deterioration	General disorders	MedDRA 18.0	Systematic Assessment	EG00016 affected393 at risk EG0018 affected396 at risk
Hallucination	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0013 affected396 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected393 at risk EG0010 affected396 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected393 at risk EG0010 affected396 at risk
Hypovolaemic shock	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Paraparesis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Pericardial effusion	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Proctalgia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Self injurious behaviour	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected393 at risk EG0015 affected396 at risk
Anxiety	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Blood bilirubin increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0012 affected396 at risk
Central nervous system infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Colitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00021 affected393 at risk EG0010 affected396 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0012 affected396 at risk
Femoral hernia incarcerated	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Gastrointestinal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0013 affected396 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0010 affected396 at risk
Hypophysitis	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0012 affected396 at risk
Hypothyroidism	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Lethargy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0011 affected396 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Malaise	General disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected393 at risk EG0011 affected396 at risk
Mucosal inflammation	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00018 affected393 at risk EG0015 affected396 at risk
Renal impairment	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0012 affected396 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Trigeminal nerve disorder	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0011 affected396 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0011 affected396 at risk
Anaemia of malignant disease	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Anal abscess	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Bladder dilatation	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Bladder obstruction	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Blood creatinine increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0011 affected396 at risk
C-reactive protein increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Central nervous system haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0012 affected396 at risk
Cerebellopontine angle tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0012 affected396 at risk
Confusional state	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0013 affected396 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected393 at risk EG0016 affected396 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG00013 affected393 at risk EG00110 affected396 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Liver function test abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0010 affected396 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0012 affected396 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0015 affected396 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Neurological symptom	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Paresis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Proctitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Pupils unequal	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG00017 affected393 at risk EG0012 affected396 at risk
Red blood cell count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Renal injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Retinal vein thrombosis	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0007 affected393 at risk EG0010 affected396 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Cavernous sinus thrombosis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Cerebral haematoma	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Cerebral infarction	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Eastern Cooperative Oncology Group performance status worsened	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0012 affected396 at risk
Enterocolitis haemorrhagic	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Febrile infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Haemoglobin decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00013 affected393 at risk EG0017 affected396 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0011 affected396 at risk
Hypopituitarism	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0010 affected396 at risk
Ileus	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Intestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Labyrinthitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Lymphangiosis carcinomatosa	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Malignant neoplasm of spinal cord	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00011 affected393 at risk EG0018 affected396 at risk
Oesophageal perforation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Papilloedema	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected393 at risk EG0011 affected396 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0011 affected396 at risk
Streptococcal bacteraemia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Viral infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Anal infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Anuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Bacterial sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Blood creatine phosphokinase decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Bone fissure	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Bradycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cardiac failure	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0011 affected396 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00059 affected393 at risk EG0016 affected396 at risk
Duodenitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Enteritis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Gastritis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Herpes zoster	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Hypersensitivity	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Lobar pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Periorbital cellulitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Peripheral swelling	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Platelet count decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0012 affected396 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Septic shock	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Spinal cord compression	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected393 at risk EG0012 affected396 at risk
Spinal cord infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0012 affected396 at risk
Venous thrombosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0012 affected396 at risk
Bronchopneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0013 affected396 at risk
Cardiac valve disease	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0013 affected396 at risk
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected393 at risk EG0013 affected396 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0012 affected396 at risk
Epilepsy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Hypertensive crisis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Lung infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG00036 affected393 at risk EG00131 affected396 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0012 affected396 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected393 at risk EG0016 affected396 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0014 affected396 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Renal failure	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected393 at risk EG0011 affected396 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0016 affected396 at risk
Thrombosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Tongue paralysis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00012 affected393 at risk EG0014 affected396 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00011 affected393 at risk EG00110 affected396 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected393 at risk EG0012 affected396 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected393 at risk EG00118 affected396 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected393 at risk EG0014 affected396 at risk
Autoimmune disorder	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Cerebrovascular disorder	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Cystitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Haematuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected393 at risk EG0016 affected396 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected393 at risk EG0010 affected396 at risk
Pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected393 at risk EG00110 affected396 at risk
Performance status decreased	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0012 affected396 at risk
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0011 affected396 at risk
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0012 affected396 at risk
Urinary retention	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0012 affected396 at risk
Urosepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Alanine aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0006 affected393 at risk EG0010 affected396 at risk
Arrhythmia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0010 affected396 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0012 affected396 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected393 at risk EG0018 affected396 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected393 at risk EG0014 affected396 at risk
Brachial plexopathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Bronchitis bacterial	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Cardiac arrest	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Chronic gastritis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Death	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0011 affected396 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0011 affected396 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
General physical condition abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0012 affected396 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected393 at risk EG0011 affected396 at risk
Infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0012 affected396 at risk
Macular degeneration	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Melaena	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Multi-organ failure	General disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0014 affected396 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Paraesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Paraplegia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Pyelonephritis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Seizure	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0006 affected393 at risk EG0013 affected396 at risk
Somnolence	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0011 affected396 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Urethral obstruction	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected393 at risk EG0011 affected396 at risk
Vasculitis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected393 at risk EG0010 affected396 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0002 affected393 at risk EG0010 affected396 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00026 affected393 at risk EG00115 affected396 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected393 at risk EG00120 affected396 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00038 affected393 at risk EG00131 affected396 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00033 affected393 at risk EG00125 affected396 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG000119 affected393 at risk EG00197 affected396 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG00020 affected393 at risk EG00113 affected396 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00020 affected393 at risk EG00110 affected396 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG00031 affected393 at risk EG00134 affected396 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00099 affected393 at risk EG00122 affected396 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00036 affected393 at risk EG00127 affected396 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG00022 affected393 at risk EG00118 affected396 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG00047 affected393 at risk EG00132 affected396 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG000144 affected393 at risk EG001120 affected396 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00032 affected393 at risk EG00144 affected396 at risk
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG00046 affected393 at risk EG00133 affected396 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG00081 affected393 at risk EG00150 affected396 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG00031 affected393 at risk EG00121 affected396 at risk
Haemoglobin decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00026 affected393 at risk EG00120 affected396 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG000126 affected393 at risk EG001104 affected396 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00081 affected393 at risk EG00127 affected396 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG000186 affected393 at risk EG00194 affected396 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00066 affected393 at risk EG00182 affected396 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00031 affected393 at risk EG00141 affected396 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG00024 affected393 at risk EG00124 affected396 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG000107 affected393 at risk EG00180 affected396 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG00079 affected393 at risk EG00181 affected396 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG00080 affected393 at risk EG00164 affected396 at risk
Pain	General disorders	MedDRA 18.0	Systematic Assessment	EG00033 affected393 at risk EG00144 affected396 at risk
Alanine aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG00026 affected393 at risk EG0019 affected396 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00044 affected393 at risk EG00157 affected396 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00056 affected393 at risk EG00174 affected396 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG00031 affected393 at risk EG00153 affected396 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG00091 affected393 at risk EG00156 affected396 at risk

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins