EMD 525797 in Subjects With Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer (PERSEUS)

• ClinicalTrials.gov Identifier: NCT01360840
• Recruitment Status: Completed
• First Posted: May 26, 2011
• Results First Posted: December 14, 2015
• Last Update Posted: December 14, 2015
• Sponsor: EMD Serono
• Information provided by (Responsible Party): EMD Serono

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Prostate Cancer Metastatic
• Interventions: Drug: EMD 525797; Other: Placebo; Other: Standard of Care (SoC)
• Enrollment: 180

Participant Flow

Recruitment Details	First/Last subject (informed consent): April 2011/December 2012. Study completion date: July 2014. Clinical data cut-off: 30 April 2013. Subjects were recruited in 11 countries (Australia, Belgium, Canada, France, Germany, Netherlands, Poland, Russia, South Africa, Spain, and USA) across the globe in 65 centers.
Pre-assignment Details	Enrolled: 283 screened for eligibility; 103 were excluded (mainly non-fulfillment of inclusion or exclusion criteria). 180 subjects were assigned to the treatment groups. Two subjects did not receive study drug administration.

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
Started	60	60	60
Completed	50	50	51
Not Completed	10	10	9
Reason Not Completed
Ongoing at data cut-off	10	10	9

Baseline Characteristics

Arm/Group Title		Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC	Total
Arm/Group Description		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.	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.	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.	Total of all reporting groups
Overall Number of Baseline Participants		60	60	60	180
Baseline Analysis Population Description		All Subjects (ALL) analysis set included subjects who signed the Informed consent document.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	60 participants	60 participants	60 participants	180 participants
		69.9 (8.43)	69.0 (7.31)	70.0 (8.88)	69.6 (8.20)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	60 participants	60 participants	60 participants	180 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	60 100.0%	60 100.0%	60 100.0%	180 100.0%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Time
Description	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 Frame	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	60	60	60
Median (95% Confidence Interval); Unit of Measure: months
	3.3; (2.8 to 4.8)	3.4; (2.8 to 5.6)	4.3; (2.8 to 6.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SoC, EMD 525797 750 mg + SoC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.39
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + SoC, EMD 525797 1500 mg + SoC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.26
	Estimation Comments	[Not Specified]

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	60	60	60
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (14.8 to NA)	NA [1]; (12.9 to NA)	NA [1]; (14.4 to NA)

[1]

The value was not estimable due to lack of events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SoC, EMD 525797 750 mg + SoC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.52 to 2.31
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + SoC, EMD 525797 1500 mg + SoC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.47 to 2.15
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Time to Tumor Progression
Description	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.
Time Frame	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	60	60	60
Median (95% Confidence Interval); Unit of Measure: months
	3.3; (2.8 to 5.4)	3.4; (2.8 to 5.6)	4.6; (2.8 to 6.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SoC, EMD 525797 750 mg + SoC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.58 to 1.44
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + SoC, EMD 525797 1500 mg + SoC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.52 to 1.27
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Number of Subjects With Presence of Tumor Response and Disease Control (DC) in Soft Tissue Lesions
Description	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.
Time Frame	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	28	22	24
Measure Type: Number; Unit of Measure: Subjects
Tumor response	1	0	1
Disease control	2	3	4

5. Secondary Outcome

Title	Number of Subjects With New Bone Lesions Compared to Baseline
Description	New bone lesions were evaluated by bone scintigraphy for subjects with bone lesions at baseline.
Time Frame	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	57	57	57
Measure Type: Number; Unit of Measure: Subjects
	40	34	34

6. Secondary Outcome

Title	Number of Subjects With Presence of DC in Bone Lesions
Description	Presence of DC in bone lesions was defined as the appearance of less than 2 new bone lesions, documented by bone scintigraphy.
Time Frame	At Weeks 13, 19 and 25

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	60	60	60
Measure Type: Number; Unit of Measure: Subjects
Week 13	4	7	7
Week 19	2	7	6
Week 25	2	4	3

7. Secondary Outcome

Title	Bone and Soft Tissue Lesions Composite Tumor Response
Description	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.
Time Frame	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	60	60	60
Measure Type: Number; Unit of Measure: Subjects
	0	0	0

8. Secondary Outcome

Title	Number of Subjects With Presence of Skeletal Related Events
Description	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.
Time Frame	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	60	60	60
Measure Type: Number; Unit of Measure: Subjects
	2	8	3

9. Secondary Outcome

Title	Number of Subjects With Presence of Prostate Specific Antigen (PSA) Response
Description	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.
Time Frame	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	60	58	60
Measure Type: Number; Unit of Measure: Subjects
	3	6	5

10. Secondary Outcome

Title	Minimum Percentage Change From Baseline in PSA Serum Concentration
Description	[Not Specified]
Time Frame	Baseline, up to data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	58	57	60
Mean (Standard Deviation); Unit of Measure: Percent change
	24.00 (86.156)	35.65 (127.677)	14.70 (50.841)

11. Secondary Outcome

Title	Minimum Percentage Change From Baseline in the Number of Circulating Tumor Cells (CTCs)
Description	[Not Specified]
Time Frame	Time from randomization until data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	29	27	22
Mean (Standard Deviation); Unit of Measure: Percent change
	49.02 (127.643)	354.74 (1038.195)	280.58 (482.653)

12. Secondary Outcome

Title	Overall Minimum Percentage Change From Previous Time Point in Circulating Tumor Cells (CTC)
Description	[Not Specified]
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	36	34	30
Mean (Standard Deviation); Unit of Measure: Percent change
	9.54 (103.225)	223.97 (868.941)	179.11 (446.428)

13. Secondary Outcome

Title	Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	60	58	60
Measure Type: Number; Unit of Measure: Subjects
TEAEs	55	49	53
Serious TEAEs	16	13	14
TEAEs leading to death	2	2	3
TEAEs Leading to Permanent Discontinuation	5	11	8

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	4	6
Mean (Standard Deviation); Unit of Measure: Liter per hour
First dose: CL (n=4, 6)	0.017 (0.007)	0.013 (0.003)
Fifth dose: CLss (n=2, 4)	0.017 (0.002)	0.010 (0.001)

15. Secondary Outcome

Title	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
Description	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).
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	4	6
Mean (Standard Deviation); Unit of Measure: liter
First dose (n=4, 6)	4.55 (1.02)	4.60 (0.74)
Fifth dose (n=2, 4)	4.81 [1] (NA)	5.18 (0.56)

[1]

The sample size of n=2 was inappropriate for Vss parameter to calculate standard deviation. Hence, it was not calculated.

16. Other Pre-specified Outcome

Title	To Explore the Relationship Between Number and/or Changes of Numbers of Biomarker and the Clinical Outcome
Description	[Not Specified]
Time Frame	From the date of randomization up to data cut-off date (30 April 2013), assessed up to 2 years

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	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
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
Arm/Group Description	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.	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.	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.
All-Cause Mortality
	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	16/60 (26.67%)	13/58 (22.41%)	14/60 (23.33%)
Blood and lymphatic system disorders
Anaemia * 1	1/60 (1.67%)	0/58 (0.00%)	3/60 (5.00%)
Cardiac disorders
Arrhythmia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Acute coronary syndrome * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Myocardial infarction * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Ear and labyrinth disorders
Vertigo * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Gastrointestinal disorders
Abdominal pain upper * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Colitis * 1	1/60 (1.67%)	0/58 (0.00%)	1/60 (1.67%)
Haematemesis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Periodontitis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Rectal haemorrhage * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
General disorders
Disease progression * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Pain * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Asthenia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Fatigue * 1	2/60 (3.33%)	0/58 (0.00%)	0/60 (0.00%)
Gait disturbance * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Infusion site extravasation * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Pyrexia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Hepatobiliary disorders
Cholecystitis acute * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Infections and infestations
Cellulitis orbital * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Osteomyelitis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Pneumonia * 1	1/60 (1.67%)	1/58 (1.72%)	0/60 (0.00%)
Pyelonephritis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Septic shock * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Toxic shock syndrome * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Urinary tract infection * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Injury, poisoning and procedural complications
Fall * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Femur fracture * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Spinal compression fracture * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Metabolism and nutrition disorders
Hyperkalaemia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Hypophosphataemia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain * 1	1/60 (1.67%)	0/58 (0.00%)	1/60 (1.67%)
Muscular weakness * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Musculoskeletal chest pain * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Musculoskeletal pain * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Arthralgia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Nervous system disorders
Spinal cord compression * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Dysaesthesia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Epiduritis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Headache * 1	1/60 (1.67%)	0/58 (0.00%)	1/60 (1.67%)
Ischaemic stroke * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Balance disorder * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Dizziness * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Memory impairment * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Syncope * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Psychiatric disorders
Confusional state * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Renal and urinary disorders
Urinary retention * 1	1/60 (1.67%)	2/58 (3.45%)	1/60 (1.67%)
Haematuria * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Anuria * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Renal failure acute * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Renal failure * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis bullous * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Pemphigoid * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Urticaria * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Vascular disorders
Orthostatis hypotension * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Hypotension * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA Version 15.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo + SoC	EMD 525797 750 mg + SoC	EMD 525797 1500 mg + SoC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	53/60 (88.33%)	47/58 (81.03%)	53/60 (88.33%)
Blood and lymphatic system disorders
Anaemia † 1	10/60 (16.67%)	6/58 (10.34%)	13/60 (21.67%)
Thrombocytopenia * 1	0/60 (0.00%)	3/58 (5.17%)	0/60 (0.00%)
Anaemia macrocytic * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Anaemia of chronic disease * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Anaemia of malignant disease * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Haemorrhagic anaemia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Leukopenia * 1	1/60 (1.67%)	0/58 (0.00%)	1/60 (1.67%)
Lymphadenopathy * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Lymphopenia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Hypochromic anaemia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Leukocytosis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Paratracheal lymphadenopathy * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Cardiac disorders
Angina pectoris * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Atrial fibrillation * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Bradycardia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Palpitations * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Supraventricular extrasystoles * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Tachycardia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Sinus bradycardia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Sinus tachycardia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Ear and labyrinth disorders
Vertigo * 1	0/60 (0.00%)	2/58 (3.45%)	2/60 (3.33%)
Hypoacusis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Tinnitus * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Eye disorders
Conjunctivitis * 1	0/60 (0.00%)	0/58 (0.00%)	2/60 (3.33%)
Eye pain * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Visual acuity reduced * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Conjunctival haemorrhage * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Ocular hyperaemia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Vision blurred * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Asthenopia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Scleral haemorrhage * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Gastrointestinal disorders
Diarrhoea * 1	5/60 (8.33%)	9/58 (15.52%)	3/60 (5.00%)
Nausea * 1	2/60 (3.33%)	6/58 (10.34%)	6/60 (10.00%)
Constipation * 1	7/60 (11.67%)	6/58 (10.34%)	3/60 (5.00%)
Vomiting * 1	2/60 (3.33%)	4/58 (6.90%)	3/60 (5.00%)
Abdominal pain upper * 1	0/60 (0.00%)	1/58 (1.72%)	2/60 (3.33%)
Dry mouth * 1	1/60 (1.67%)	3/58 (5.17%)	0/60 (0.00%)
Paraesthesia oral * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Periodonditis * 1	0/60 (0.00%)	0/58 (0.00%)	2/60 (3.33%)
Abdominal distension * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Abdominal pain † 1	2/60 (3.33%)	0/58 (0.00%)	1/60 (1.67%)
Abdominal pain lower * 1	1/60 (1.67%)	1/58 (1.72%)	0/60 (0.00%)
Aphthous stomatitis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Cheilitis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Colitis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Dental caries * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Eructation * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Gastritis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Odynophagia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Parotid gland enlargement * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Proctalgia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Rectal haemorrhage * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Stomatitis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Gingivitis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Haematochezia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Haemorrhoids * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
oral pain * 1	2/60 (3.33%)	0/58 (0.00%)	0/60 (0.00%)
Pancreatitis acute * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Peptic ulcer * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Proctitis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Retching * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
General disorders
Fatigue * 1	12/60 (20.00%)	10/58 (17.24%)	9/60 (15.00%)
Influenza like illness * 1	4/60 (6.67%)	8/58 (13.79%)	3/60 (5.00%)
Asthenia * 1	9/60 (15.00%)	3/58 (5.17%)	6/60 (10.00%)
oedema peripheral * 1	1/60 (1.67%)	7/58 (12.07%)	1/60 (1.67%)
Pyrexia * 1	2/60 (3.33%)	4/58 (6.90%)	4/60 (6.67%)
Pain * 1	1/60 (1.67%)	2/58 (3.45%)	3/60 (5.00%)
Chest pain * 1	0/60 (0.00%)	2/58 (3.45%)	1/60 (1.67%)
Spinal pain * 1	1/60 (1.67%)	2/58 (3.45%)	1/60 (1.67%)
Non-cardiac chest pain * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Chest discomfort * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Crying * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Feeling hot * 1	1/60 (1.67%)	1/58 (1.72%)	0/60 (0.00%)
Gait disturbance * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Hypothermia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Malaise * 1	3/60 (5.00%)	1/58 (1.72%)	0/60 (0.00%)
Temperature intolerance * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Hepatobiliary disorders
Cholecystitis acute * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Cholelithiasis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Hepatomegaly * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Immune system disorders
Contrast media allergy † 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Infections and infestations
Nasopharyngitis * 1	2/60 (3.33%)	5/58 (8.62%)	2/60 (3.33%)
Rhinitis * 1	0/60 (0.00%)	2/58 (3.45%)	2/60 (3.33%)
Urinary tract infection * 1	2/60 (3.33%)	3/58 (5.17%)	1/60 (1.67%)
Upper respiratory tract infection * 1	0/60 (0.00%)	1/58 (1.72%)	2/60 (3.33%)
Bronchitis * 1	1/60 (1.67%)	0/58 (0.00%)	2/60 (3.33%)
Oral candidiasis * 1	0/60 (0.00%)	0/58 (0.00%)	2/60 (3.33%)
Anal fungal infection * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Fungal oesophagitis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Fungal skin infection * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Influenza * 1	4/60 (6.67%)	1/58 (1.72%)	0/60 (0.00%)
Oral fungal infection * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Perineal infection * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Pyelonephritis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Tooth abscess * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Tooth infection * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Viral infection * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Viral upper respiratory tract infection * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Wound infection * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Wound sepsis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Cystitis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Gastroenteritis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Herpes simplex * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Skin candida * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Injury, poisoning and procedural complications
Contusion * 1	0/60 (0.00%)	2/58 (3.45%)	0/60 (0.00%)
Fall * 1	2/60 (3.33%)	1/58 (1.72%)	1/60 (1.67%)
Excoriation * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Infusion related reaction * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Ligament sprain * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Skin wound * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Hand fracture * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Tooth fracture * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Investigations
Weight decreased * 1	6/60 (10.00%)	1/58 (1.72%)	5/60 (8.33%)
Blood alkaline phosphatase increased * 1	3/60 (5.00%)	1/58 (1.72%)	4/60 (6.67%)
Blood creatinine increased * 1	1/60 (1.67%)	2/58 (3.45%)	3/60 (5.00%)
Fibrin D dimer increased * 1	4/60 (6.67%)	2/58 (3.45%)	3/60 (5.00%)
C-reactive protein increased * 1	0/60 (0.00%)	1/58 (1.72%)	3/60 (5.00%)
Aspartate aminotransferase increased * 1	1/60 (1.67%)	2/58 (3.45%)	1/60 (1.67%)
Creatinine renal clearance decreased * 1	0/60 (0.00%)	0/58 (0.00%)	3/60 (5.00%)
Alanine aminotransferase increased * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Blood potassium increased † 1	0/60 (0.00%)	0/58 (0.00%)	2/60 (3.33%)
Blood urea increased * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Platelet count decreased * 1	0/60 (0.00%)	2/58 (3.45%)	0/60 (0.00%)
Activated partial thromboplastin time prolonged * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Blood cholesterol increased * 1	1/60 (1.67%)	0/58 (0.00%)	1/60 (1.67%)
Blood creatinine increased * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Blood urine present * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Calcium ionised decreased * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Cardiac murmur * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Gamma-glutamyl transferase increased * 1	1/60 (1.67%)	1/58 (1.72%)	0/60 (0.00%)
Haemoglobin decreased * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
International normalised ratio decreased * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Liver function test abnormal * 1	1/60 (1.67%)	1/58 (1.72%)	0/60 (0.00%)
Lymphocyte count decreased * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
White blood cell count decreased * 1	1/60 (1.67%)	0/58 (0.00%)	1/60 (1.67%)
Electrocardiogram ST-T segment abnormal * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Prostatic specific antigen increased * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Metabolism and nutrition disorders
Decreased appetite * 1	5/60 (8.33%)	8/58 (13.79%)	4/60 (6.67%)
Hypocalcaemia * 1	3/60 (5.00%)	1/58 (1.72%)	7/60 (11.67%)
Hypercholesterolaemia * 1	0/60 (0.00%)	2/58 (3.45%)	3/60 (5.00%)
Diabetes mellitus * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Hyperglycaemia * 1	2/60 (3.33%)	1/58 (1.72%)	1/60 (1.67%)
Hyperkalaemia * 1	1/60 (1.67%)	0/58 (0.00%)	2/60 (3.33%)
Fluid overload * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Glucose tolerance impaired * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Gout * 1	1/60 (1.67%)	1/58 (1.72%)	0/60 (0.00%)
Hypoalbuminaemia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Hypoglycaemia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Type 2 diabetes mellitus * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Dehydration * 1	2/60 (3.33%)	0/58 (0.00%)	0/60 (0.00%)
Hypermagnesaemia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Hyperuricaemia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Hypokalaemia * 1	2/60 (3.33%)	0/58 (0.00%)	0/60 (0.00%)
Hyponatraemia * 1	2/60 (3.33%)	0/58 (0.00%)	0/60 (0.00%)
Vitamin D deficiency * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain * 1	10/60 (16.67%)	9/58 (15.52%)	6/60 (10.00%)
Arthralgia * 1	7/60 (11.67%)	7/58 (12.07%)	7/60 (11.67%)
Bone pain * 1	7/60 (11.67%)	6/58 (10.34%)	6/60 (10.00%)
Pain in extremity * 1	4/60 (6.67%)	8/58 (13.79%)	3/60 (5.00%)
Musculoskeletal pain * 1	3/60 (5.00%)	6/58 (10.34%)	3/60 (5.00%)
Myalgia † 1	4/60 (6.67%)	3/58 (5.17%)	4/60 (6.67%)
Muscular weakness * 1	2/60 (3.33%)	1/58 (1.72%)	4/60 (6.67%)
Musculoskeletal chest pain * 1	1/60 (1.67%)	3/58 (5.17%)	1/60 (1.67%)
Neck pain * 1	1/60 (1.67%)	3/58 (5.17%)	1/60 (1.67%)
Flank pain * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Osteoarthritis * 1	0/60 (0.00%)	2/58 (3.45%)	0/60 (0.00%)
Trigger finger * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Bone swelling * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Bunion * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Cervical spinal stenosis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Groin pain * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Mobility decreased * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Musculoskeletal discomfort * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Pain in jaw * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Spinal osteoarthritis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Intervertebral disc degeneration * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Osteopenia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain * 1	0/60 (0.00%)	2/58 (3.45%)	0/60 (0.00%)
Skin papilloma * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Squamous cell carcinoma * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Tumor invasion * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Bone neoplasm malignant * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Nervous system disorders
Dizziness * 1	2/60 (3.33%)	1/58 (1.72%)	3/60 (5.00%)
Dysgeusia * 1	1/60 (1.67%)	1/58 (1.72%)	3/60 (5.00%)
Headache * 1	5/60 (8.33%)	1/58 (1.72%)	2/60 (3.33%)
Hypoaesthesia * 1	0/60 (0.00%)	1/58 (1.72%)	2/60 (3.33%)
Paraesthesia * 1	0/60 (0.00%)	0/58 (0.00%)	2/60 (3.33%)
Sciatica * 1	1/60 (1.67%)	0/58 (0.00%)	2/60 (3.33%)
Amnesia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Cervical root pain * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Depressed level of consciousness * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Dysaesthesia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Epiduritis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Head discomfort * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Neuropathy peripheral * 1	1/60 (1.67%)	1/58 (1.72%)	0/60 (0.00%)
Paraplegia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Spinal cord compression * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Syncope * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Vascular encephalopathy * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Burning sensation * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Disturbance in attention † 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Memory impairment * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Paresis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Tremor * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Psychiatric disorders
Insomnia * 1	3/60 (5.00%)	2/58 (3.45%)	3/60 (5.00%)
Depression * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Initial insomnia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Mood altered * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Anxiety * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Confusional state * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Stress * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Renal and urinary disorders
Haematuria * 1	3/60 (5.00%)	4/58 (6.90%)	3/60 (5.00%)
Proteinuria * 1	1/60 (1.67%)	1/58 (1.72%)	2/60 (3.33%)
Urinary retention * 1	0/60 (0.00%)	2/58 (3.45%)	1/60 (1.67%)
Calculus urinary * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Dysuria * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Nocturia * 1	0/60 (0.00%)	2/58 (3.45%)	0/60 (0.00%)
Renal failure * 1	2/60 (3.33%)	0/58 (0.00%)	2/60 (3.33%)
Azotaemia * 1	1/60 (1.67%)	0/58 (0.00%)	1/60 (1.67%)
Hydronephrosis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Leukocyturia * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Renal pain * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Stress urinary incontinence * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Ureteric obstruction * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Urinary incontinence * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Urinary tract obstruction * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Renal failure acute * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Pelvic pain * 1	0/60 (0.00%)	1/58 (1.72%)	1/60 (1.67%)
Balanitis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Penile pain * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Perineal pain * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Gynaecomastia * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Testicular pain * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	1/60 (1.67%)	5/58 (8.62%)	5/60 (8.33%)
Dyspnoea * 1	1/60 (1.67%)	3/58 (5.17%)	3/60 (5.00%)
Epistaxis * 1	1/60 (1.67%)	1/58 (1.72%)	3/60 (5.00%)
Dyspnoea exertional * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Nasal congestion * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Pleural effusion * 1	0/60 (0.00%)	2/58 (3.45%)	0/60 (0.00%)
Rhinorrhoea * 1	0/60 (0.00%)	2/58 (3.45%)	0/60 (0.00%)
Sinus congestion † 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Dysphonia * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Haemoptysis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Oropharyngeal pain * 1	1/60 (1.67%)	0/58 (0.00%)	1/60 (1.67%)
Sputum retention * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Skin and subcutaneous tissue disorders
Pruritus * 1	1/60 (1.67%)	4/58 (6.90%)	6/60 (10.00%)
Rash * 1	1/60 (1.67%)	3/58 (5.17%)	5/60 (8.33%)
Rash pruritic * 1	0/60 (0.00%)	3/58 (5.17%)	2/60 (3.33%)
Erythema * 1	0/60 (0.00%)	1/58 (1.72%)	3/60 (5.00%)
Pruritus generalised * 1	0/60 (0.00%)	2/58 (3.45%)	2/60 (3.33%)
Dry skin * 1	0/60 (0.00%)	1/58 (1.72%)	2/60 (3.33%)
Hyperhidrosis * 1	1/60 (1.67%)	2/58 (3.45%)	0/60 (0.00%)
Skin lesion * 1	1/60 (1.67%)	1/58 (1.72%)	1/60 (1.67%)
Urticaria * 1	0/60 (0.00%)	2/58 (3.45%)	0/60 (0.00%)
Actinic keratosis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Angioedema * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Dermatitis bullous * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Ecchymosis * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Eczema * 1	1/60 (1.67%)	1/58 (1.72%)	0/60 (0.00%)
Eczema asteatotic * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Generalised erythema * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Hypertrichosis * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Intertrigo * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Lentigo * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Papule * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Pemphigus * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Rash generalised * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Rash maculo-papular * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Skin hyperpigmentation * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Subcutaneous nodule * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Swelling face * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Dermatitis * 1	1/60 (1.67%)	0/58 (0.00%)	0/60 (0.00%)
Vascular disorders
Hot flush * 1	3/60 (5.00%)	2/58 (3.45%)	2/60 (3.33%)
Hypertension * 1	3/60 (5.00%)	1/58 (1.72%)	2/60 (3.33%)
Hypotension * 1	2/60 (3.33%)	2/58 (3.45%)	1/60 (1.67%)
Orthostatic hypertension * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
Orthostatic hypotension * 1	0/60 (0.00%)	0/58 (0.00%)	1/60 (1.67%)
Peripheral coldness * 1	0/60 (0.00%)	1/58 (1.72%)	0/60 (0.00%)
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA Version 15.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

 

Results Point of Contact

• Name/Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA
• Phone: +49-6151-72-5200
• EMail: service@merckgroup.com

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT01360840
• Other Study ID Numbers: EMR 62242-006
• First Submitted: April 15, 2011
• First Posted: May 26, 2011
• Results First Submitted: July 24, 2015
• Results First Posted: December 14, 2015
• Last Update Posted: December 14, 2015