EMD 525797 in Subjects With Asymptomatic or Mildly Sympto... | NCT01360840

Label	Type	Intervention Names
Placebo + Standard of care (SoC)	Placebo Comparator	Other: Placebo Other: Standard of Care (SoC)
EMD 525797 750 mg + SoC	Experimental	Drug: EMD 525797 Other: Standard of Care (SoC)
EMD 525797 1500 mg + SoC	Experimental	Drug: EMD 525797 Other: Standard of Care (SoC)

Name	Type	Description	Arm Group Labels	Other Names
EMD 525797	Drug	Subjects will be administered with EMD 525797 at a dose of 1500 milligram (mg) (diluted with 0.9 percent [%] sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons.

Measure	Description	Time Frame
Progression Free Survival (PFS) Time	PFS was defined as time from randomization until the first documented sign of objective radiographic disease progression (ORDP) or death from any cause. Death was considered as an event only if it was reported within 12 weeks after last tumor assessment without progression. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy. Assessment was based on Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) modified as per Prostate Cancer Working Group 2 (PCWG-2); Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression/fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated.	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Measure	Description	Time Frame
Overall Survival	Overall Survival was defined as the time from the date of randomization to the date of death from any cause.	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years
Time to Tumor Progression

Measure	Description	Time Frame
To Explore the Relationship Between Number and/or Changes of Numbers of Biomarker and the Clinical Outcome		From the date of randomization up to data cut-off date (30 April 2013), assessed up to 2 years

Name	Affiliation	Role
Medical Responsible	EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Pleasant Hill	California		United States
Research Site

ID	Title	Description
FG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the standard of care (SoC) consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression Free Survival (PFS) Time

PFS was defined as time from randomization until the first documented sign of objective radiographic disease progression (ORDP) or death from any cause. Death was considered as an event only if it was reported within 12 weeks after last tumor assessment without progression. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy. Assessment was based on Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) modified as per Prostate Cancer Working Group 2 (PCWG-2); Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression/fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated.

Intention-to-treat (ITT) analysis set included all the subjects who were randomized in the study.

Posted

Median

95% Confidence Interval

months

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG002	EMD 525797 1500 mg + SoC	Subjects were administered with EMD 525797 at a dose of 1500 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Units	Counts
Participants	OG00060 OG00160 OG00260

Title

Denominators

Categories

Title	Measurements
	OG0003.3(2.8 to 4.8) OG0013.4(2.8 to 5.6) OG0024.3(2.8 to 6.6)

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						Cox Proportional Hazard	0.89			2-Sided	95	0.57	1.39				No	Superiority or Other
OG000 OG002

Secondary

Overall Survival

Overall Survival was defined as the time from the date of randomization to the date of death from any cause.

ITT analysis set included all the subjects who were randomized in the study.

Posted

Median

95% Confidence Interval

months

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Time to Tumor Progression

Time to tumor progression was defined as the time from the date of randomization to the date of ORDP. ORDP was defined as: Bone lesion progression (2 or more new bone lesions compared to baseline) assessed with bone scintigraphy, which had to be confirmed by bone scintigraphy 6 weeks later if subjects remained asymptomatic or mildly symptomatic. Assessments were to be based on RECIST v1.0 modified according to PCWG-2; Soft-tissue lesion progression assessed with CT scans according to RECIST v1.0 modified as per PCWG-2; Presence of skeletal events defined as cord compression or fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms, based on the investigator's discretion; Non-radiological events, including emergency bone irradiation and surgery, were not investigated.

ITT analysis set included all the subjects who were randomized in the study.

Posted

Median

95% Confidence Interval

months

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions

Presence of tumor response in soft tissue lesions was defined as the presence of at least 1 confirmed complete response (CR) or confirmed partial response (PR) in soft tissue lesions, documented by computed tomography (CT) scans. Presence of DC in soft tissue lesions was defined as the presence of at least 1 confirmed CR or confirmed PR or stable disease (SD) lasting at least 12 weeks after randomization. Tumor response assessments were based on RECIST v1.0 modified according to the PCWG-2. The response was evaluated for subjects with measurable disease at baseline. According to RECIST v1.0, CR=disappearance of all target and non-target lesions; PR=at least 30% decrease in the sum of the longest diameter of target lesions and non-complete response/non-progressive disease in non-target lesions.

ITT analysis set included all the subjects who were randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Posted

Number

Subjects

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Number of Subjects With New Bone Lesions Compared to Baseline

New bone lesions were evaluated by bone scintigraphy for subjects with bone lesions at baseline.

ITT analysis set included all the subjects randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Posted

Number

Subjects

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Number of Subjects With Presence of DC in Bone Lesions

Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions, documented by bone scintigraphy.

ITT analysis set included all the subjects randomized in the study.

Posted

Number

Subjects

At Weeks 13, 19 and 25

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Bone and Soft Tissue Lesions Composite Tumor Response

Bone and soft tissue lesions composite tumor response was defined as the presence of both a confirmed CR or PR, documented by CT scans, and a DC in bone lesions, documented by bone scintigraphy. CR was defined as disappearance of all target and non-target lesions and PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions and non-complete response/non-progressive disease in non-target lesions. Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions.

ITT analysis set included all the subjects who were randomized in the study.

Posted

Number

Subjects

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Number of Subjects With Presence of Skeletal Related Events

Presence of skeletal related events was defined as cord compression or fracture documented via a scheduled or unscheduled radiographic assessment triggered by increased pain or other signs and/or symptoms at the investigator discretion. Non-radiological events, including emergency bone irradiation and surgery, were not investigated.

ITT analysis set included all the subjects who were randomized in the study.

Posted

Number

Subjects

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response

PSA response was defined as a decrease greater than 50 percent (%) in PSA value from baseline for 2 consecutive evaluations greater than or equal to (>=) 3 Weeks apart.

ITT analysis set included all the subjects who were randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Posted

Number

Subjects

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Minimum Percentage Change From Baseline in PSA Serum Concentration

ITT analysis set included all the subjects who were randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Posted

Mean

Standard Deviation

Percent change

Baseline, up to data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs)

ITT analysis set included all the subjects who were randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Posted

Mean

Standard Deviation

Percent change

Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC)

ITT analysis set included all the subjects who were randomized in the study. "N" signifies the total number of subjects evaluable for this outcome measure.

Posted

Mean

Standard Deviation

Percent change

Cycle 1, Day 1 (Week 1): pre-dose, Cycle 3, Day 1 (Week 7): pre-dose, and Cycle 5, Day 1 (Week 13): pre-dose

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Secondary

Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation

An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as those AEs that started between first dose of study drug and up to 50 days after last dose.

The Safety analysis set included all the randomized subjects who received at least 1 dose of planned trial treatment and had at least one safety assessment following the trial treatment.

Posted

Number

Subjects

From the first dose of study drug administration until 50 days after the last dose of study drug administration or until cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001

Secondary

Pharmacokinetic Parameter: Clearance of Intravenously Administered EMD 525797 After First Dose (CL) and Clearance in Steady State of EMD52597 After Fifth Dose (CLss)

The apparent total body clearance of drug following intravenous administration (CL); The apparent total body clearance of drug at steady state following intravenous administration (CLss).

Pharmacokinetic Analysis Set (PKA) included all the randomized subjects who received at least the first dose of the trial drug and provided sufficient data for a concentration time profile for EMD 525797. "n" signifies the number of subjects evaluable for each category in the evaluated group, respectively.

Posted

Mean

Standard Deviation

Liter per hour

Cycle 1 (Week 1) and cycle 5 (Week 13): Day 1: pre-dose, End of Infusion (EOI), 4, 8, 24, 48, 96, 168, 336, and 504 hours after start of infusion; Cycles 3 and 4 (Weeks 7 and 10), Day 1: pre-dose; Cycle 7 (Week 19), Day 1: pre-dose and EOI

ID	Title	Description
OG000	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001

Secondary

Pharmacokinetic Parameter: Volume of Distribution of EMD 525797 After the First Dose (V) and in Steady State After the Fifth Dose (Vss) of Intravenous Infusion

The apparent volume of distribution during the terminal phase following intravenous administration (V). The estimate of the apparent volume of distribution at steady state following intravenous administration (Vss).

PKA included all the randomized subjects who received at least the first dose of the trial drug and provided sufficient data for a concentration time profile for EMD 525797. "n" signifies the number of subjects evaluable for each category in the evaluated group, respectively.

Posted

Mean

Standard Deviation

liter

ID	Title	Description
OG000	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 1500 mg + SoC

Other Pre-specified

To Explore the Relationship Between Number and/or Changes of Numbers of Biomarker and the Clinical Outcome

Data for this outcome measure was presented graphically as per planned analysis but not statistically summarized.

Posted

From the date of randomization up to data cut-off date (30 April 2013), assessed up to 2 years

ID	Title	Description
OG000	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
OG001	EMD 525797 1500 mg + SoC	Subjects were administered with EMD 525797 at a dose of 1500 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0023 affected60 at risk
Arrhythmia	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Myocardial infarction	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Vertigo	Ear and labyrinth disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Colitis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Haematemesis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Periodontitis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Disease progression	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Pain	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Asthenia	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Fatigue	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Gait disturbance	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Infusion site extravasation	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Pyrexia	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Cellulitis orbital	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Osteomyelitis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Pneumonia	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Pyelonephritis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Septic shock	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Toxic shock syndrome	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Spinal cord compression	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Dysaesthesia	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Epiduritis	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Headache	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Ischaemic stroke	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Balance disorder	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Dizziness	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Memory impairment	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Syncope	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Confusional state	Psychiatric disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Urinary retention	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0012 affected58 at risk EG0021 affected60 at risk
Haematuria	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Anuria	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Renal failure acute	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Renal failure	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Pemphigoid	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Orthostatis hypotension	Vascular disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Hypotension	Vascular disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 15.0	Systematic Assessment	EG00010 affected60 at risk EG0016 affected58 at risk EG00213 affected60 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0013 affected58 at risk EG0020 affected60 at risk
Anaemia macrocytic	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Anaemia of chronic disease	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Anaemia of malignant disease	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Haemorrhagic anaemia	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Hypochromic anaemia	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Paratracheal lymphadenopathy	Blood and lymphatic system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Angina pectoris	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Atrial fibrillation	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Bradycardia	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Palpitations	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Tachycardia	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Sinus bradycardia	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Sinus tachycardia	Cardiac disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Vertigo	Ear and labyrinth disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0022 affected60 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Conjunctivitis	Eye disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Eye pain	Eye disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Visual acuity reduced	Eye disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Ocular hyperaemia	Eye disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Vision blurred	Eye disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Asthenopia	Eye disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Scleral haemorrhage	Eye disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0005 affected60 at risk EG0019 affected58 at risk EG0023 affected60 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0016 affected58 at risk EG0026 affected60 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0007 affected60 at risk EG0016 affected58 at risk EG0023 affected60 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0014 affected58 at risk EG0023 affected60 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0022 affected60 at risk
Dry mouth	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0013 affected58 at risk EG0020 affected60 at risk
Paraesthesia oral	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Periodonditis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0002 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Aphthous stomatitis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Cheilitis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Colitis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Dental caries	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Eructation	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Gastritis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Odynophagia	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Parotid gland enlargement	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Proctalgia	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Stomatitis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Gingivitis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Haematochezia	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
oral pain	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Peptic ulcer	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Proctitis	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Retching	Gastrointestinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Fatigue	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG00012 affected60 at risk EG00110 affected58 at risk EG0029 affected60 at risk
Influenza like illness	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0004 affected60 at risk EG0018 affected58 at risk EG0023 affected60 at risk
Asthenia	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0009 affected60 at risk EG0013 affected58 at risk EG0026 affected60 at risk
oedema peripheral	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0017 affected58 at risk EG0021 affected60 at risk
Pyrexia	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0014 affected58 at risk EG0024 affected60 at risk
Pain	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0012 affected58 at risk EG0023 affected60 at risk
Chest pain	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0021 affected60 at risk
Spinal pain	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0012 affected58 at risk EG0021 affected60 at risk
Non-cardiac chest pain	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Chest discomfort	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Crying	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Feeling hot	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Gait disturbance	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Hypothermia	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Malaise	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0003 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Temperature intolerance	General disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Hepatomegaly	Hepatobiliary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Contrast media allergy	Immune system disorders	MedDRA Version 15.0	Systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Nasopharyngitis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0015 affected58 at risk EG0022 affected60 at risk
Rhinitis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0022 affected60 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0013 affected58 at risk EG0021 affected60 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0022 affected60 at risk
Bronchitis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Oral candidiasis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Anal fungal infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Fungal oesophagitis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Fungal skin infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Influenza	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0004 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Oral fungal infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Perineal infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Pyelonephritis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Tooth abscess	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Tooth infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Viral infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Wound infection	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Wound sepsis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Cystitis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Gastroenteritis	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Herpes simplex	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Skin candida	Infections and infestations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Fall	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Skin wound	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Weight decreased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0006 affected60 at risk EG0011 affected58 at risk EG0025 affected60 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0003 affected60 at risk EG0011 affected58 at risk EG0024 affected60 at risk
Blood creatinine increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0012 affected58 at risk EG0023 affected60 at risk
Fibrin D dimer increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0004 affected60 at risk EG0012 affected58 at risk EG0023 affected60 at risk
C-reactive protein increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0023 affected60 at risk
Aspartate aminotransferase increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0012 affected58 at risk EG0021 affected60 at risk
Creatinine renal clearance decreased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0023 affected60 at risk
Alanine aminotransferase increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Blood potassium increased	Investigations	MedDRA Version 15.0	Systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Blood urea increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Platelet count decreased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Blood cholesterol increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Blood creatinine increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Blood urine present	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Calcium ionised decreased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Cardiac murmur	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Gamma-glutamyl transferase increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Haemoglobin decreased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
International normalised ratio decreased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Liver function test abnormal	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Lymphocyte count decreased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
White blood cell count decreased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Electrocardiogram ST-T segment abnormal	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Prostatic specific antigen increased	Investigations	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0005 affected60 at risk EG0018 affected58 at risk EG0024 affected60 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0003 affected60 at risk EG0011 affected58 at risk EG0027 affected60 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0023 affected60 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Gout	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG00010 affected60 at risk EG0019 affected58 at risk EG0026 affected60 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0007 affected60 at risk EG0017 affected58 at risk EG0027 affected60 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0007 affected60 at risk EG0016 affected58 at risk EG0026 affected60 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0004 affected60 at risk EG0018 affected58 at risk EG0023 affected60 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0003 affected60 at risk EG0016 affected58 at risk EG0023 affected60 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Systematic Assessment	EG0004 affected60 at risk EG0013 affected58 at risk EG0024 affected60 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0011 affected58 at risk EG0024 affected60 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0013 affected58 at risk EG0021 affected60 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0013 affected58 at risk EG0021 affected60 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Bone swelling	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Bunion	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Mobility decreased	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Osteopenia	Musculoskeletal and connective tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Tumor pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Tumor invasion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Bone neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Dizziness	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0011 affected58 at risk EG0023 affected60 at risk
Dysgeusia	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0023 affected60 at risk
Headache	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0005 affected60 at risk EG0011 affected58 at risk EG0022 affected60 at risk
Hypoaesthesia	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0022 affected60 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Sciatica	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Amnesia	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Cervical root pain	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Dysaesthesia	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Epiduritis	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Head discomfort	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Paraplegia	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Spinal cord compression	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Syncope	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Vascular encephalopathy	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Burning sensation	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Disturbance in attention	Nervous system disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Memory impairment	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Paresis	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Tremor	Nervous system disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Insomnia	Psychiatric disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0003 affected60 at risk EG0012 affected58 at risk EG0023 affected60 at risk
Depression	Psychiatric disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Initial insomnia	Psychiatric disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Mood altered	Psychiatric disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Anxiety	Psychiatric disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Confusional state	Psychiatric disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Stress	Psychiatric disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Haematuria	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0003 affected60 at risk EG0014 affected58 at risk EG0023 affected60 at risk
Proteinuria	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0022 affected60 at risk
Urinary retention	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0021 affected60 at risk
Calculus urinary	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Dysuria	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Nocturia	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Renal failure	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0010 affected58 at risk EG0022 affected60 at risk
Azotaemia	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Leukocyturia	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Renal pain	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Stress urinary incontinence	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Renal failure acute	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Pelvic pain	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Balanitis	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Penile pain	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Perineal pain	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Gynaecomastia	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Testicular pain	Renal and urinary disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0015 affected58 at risk EG0025 affected60 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0013 affected58 at risk EG0023 affected60 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0023 affected60 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Sputum retention	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0014 affected58 at risk EG0026 affected60 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0013 affected58 at risk EG0025 affected60 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0013 affected58 at risk EG0022 affected60 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0023 affected60 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0022 affected60 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0022 affected60 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0021 affected60 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0012 affected58 at risk EG0020 affected60 at risk
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Eczema asteatotic	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Generalised erythema	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Hypertrichosis	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Intertrigo	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Lentigo	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Papule	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Pemphigus	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Subcutaneous nodule	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0001 affected60 at risk EG0010 affected58 at risk EG0020 affected60 at risk
Hot flush	Vascular disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0003 affected60 at risk EG0012 affected58 at risk EG0022 affected60 at risk
Hypertension	Vascular disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0003 affected60 at risk EG0011 affected58 at risk EG0022 affected60 at risk
Hypotension	Vascular disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0002 affected60 at risk EG0012 affected58 at risk EG0021 affected60 at risk
Orthostatic hypertension	Vascular disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk
Orthostatic hypotension	Vascular disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0010 affected58 at risk EG0021 affected60 at risk
Peripheral coldness	Vascular disorders	MedDRA Version 15.0	Non-systematic Assessment	EG0000 affected60 at risk EG0011 affected58 at risk EG0020 affected60 at risk

ID	Term
D019984	Quality Indicators, Health Care
D011787	Quality of Health Care
D006298	Health Services Administration
D017530	Health Care Quality, Access, and Evaluation

ID	Title	Description
BG000	Placebo + SoC	Subjects were administered with placebo 0.9% sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
BG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
BG002	EMD 525797 1500 mg + SoC	Subjects were administered with EMD 525797 at a dose of 1500 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo + SoC	Subjects were administered with placebo 0.9 percent (%) sodium chloride as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.	16	60	53	60
EG001	EMD 525797 750 mg + SoC	Subjects were administered with EMD 525797 at a dose of 750 milligram (mg) (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.	13	58	47	58
EG002	EMD 525797 1500 mg + SoC	Subjects were administered with EMD 525797 at a dose of 1500 mg (diluted with 0.9% sodium chloride) as a 1-hour intravenous infusion every 3 Weeks until disease progression or unacceptable toxicity, whichever comes first, unless the subject stopped the trial treatment for other reasons. All the subjects followed the SoC consisting of the continued treatment with luteinizing-hormone releasing hormone agonists (or antagonists). In order to avoid any confounding effects, bisphosphonate treatment was initiated 2 days before start of treatment with EMD 525797.	14	60	53	60