Study Comparing Orteronel Plus Prednisone in Participants... | NCT01193257

ID	Type	Description
2010-018662-23	EudraCT Number
CTR20131423	Registry Identifier	SFDA CTR
0991413212	Registry Identifier	TCTIN
C21005	Registry Identifier	NRES
U1111-1181-8040	Registry Identifier	WHO

Status Module

Label	Type	Description	Intervention Names
Orteronel + prednisone	Experimental		Drug: Orteronel Drug: Prednisone
Placebo + prednisone	Placebo Comparator		Drug: Prednisone Drug: Orteronel Placebo

Name	Type	Description	Arm Group Labels	Other Names
Orteronel	Drug	Orteronel tablets	Orteronel + prednisone	TAK-700

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Survival	Overall survival was calculated from the date of participant randomization to the date of participant death due to any cause. Participants without documentation of death at time of the analysis were censored as of the date the participant was last known to be alive, or the data cutoff date, whichever was earlier.	Baseline until death (approximately up to 4.5 years)

Secondary Outcomes

Measure	Description	Time Frame
Radiographic Progression-free Survival (rPFS)	rPFS was defined as the time from randomization until radiographic disease progression or death due to any cause, whichever occurred first. Radiographic disease progression was defined as the occurrence of 1 or more of the following: The appearance of 2 or more new lesions on radionuclide bone scan as defined by prostate cancer working group (PCWG)2; Should 2 or more new bone lesions be evident at the first assessment (8-week assessment) on treatment, 2 or more additional new lesions must have been evident on a confirmatory assessment at least 6 weeks later; One or more new soft tissue/visceral organ lesions identified by computed tomography (CT)/magnetic resonance imaging (MRI); Progression as defined by response evaluation criteria in solid tumors (RECIST) 1.1 criteria.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Each participant must meet all of the following inclusion criteria:

Voluntary written consent
Male 18 years or older
Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma
Radiograph-documented metastatic disease
Progressive disease
Prior surgical castration or concurrent use of an agent for medical castration
Progressive disease during or following 1 or 2 regimens of cytotoxic chemotherapy, 1 of which must have included docetaxel. Must have received greater than or equal to (>=) 360 milligram per square meter (mg/m^2) of docetaxel within a 6-month period. Participants who were clearly intolerant to docetaxel or develop progressive disease before receiving >= 360 mg/m^2 are also eligible if they have received at least 225 mg/m^2 of docetaxel within a 6-month period and meet the other study entry criteria.
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Even if surgically sterilized, participants must practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, OR Abstain from heterosexual intercourse
Screening laboratory values as specified in protocol
Stable medical condition
Life expectancy of 6 months or more
Participants who have had up to 2 prior chemotherapy treatments are eligible to participate

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

Known hypersensitivity to orteronel, prednisone or gonadotropin-releasing hormone (GnRH) analogue
Received prior therapy with orteronel, aminoglutethimide, ketoconazole or abiraterone
Any other therapies for prostate cancer, except for GnRH analogue therapy, must be discontinued 2 weeks before the first dose of study drug
Radioisotope therapy or external beam radiation therapy within 4 weeks of first dose of study drug
Documented central nervous system metastases
Treatment with any investigational compound within 30 days prior to first dose of study drug (Participants who are in long-term follow-up following active treatment in other trials are eligible)
Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected
Uncontrolled cardiovascular condition as specified in study protocol
Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
Unwilling or unable to comply with protocol
Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel
Uncontrolled nausea, vomiting, or diarrhea despite appropriate medical therapy
Prostate cancer confined to just the prostrate bed or immediate adjacent tissue

Name	Affiliation	Role
Medical Monitor	Millennium Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Anchorage	Alaska	99508	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29272162	Derived	Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, Saad F, de Wit R, Aftab DT, Hirmand M, Limon A, Fizazi K, Fleisher M, de Bono JS, Scher HI. Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials. J Clin Oncol. 2018 Feb 20;36(6):572-580. doi: 10.1200/JCO.2017.75.2998. Epub 2017 Dec 22.
26031410

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
FG001	Orteronel + Prednisone

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
BG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00069.4± 7.95 BG00169.2± 7.82 BG00269.3± 7.86

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00045 BG001107 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG0001 BG0014 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Canada

Title	Measurements
	BG00011 BG00121 BG002

Height

Height data was available for 1096 participants as follows: n= 364, 732.

Mean

Standard Deviation

centimeter (cm)

Title

Denominators

Categories

Title	Measurements
	BG000171.33± 7.675 BG001172.52± 7.156

Weight

Weight data was available for 1098 participants as follows: n= 365, 733.

Mean

Standard Deviation

kilogram (kg)

Title

Denominators

Categories

Title	Measurements
	BG00079.85± 15.183 BG00182.77± 15.200

Body mass index (BMI)

BMI data was available for 1095 participants as follows: n= 364, 731.

Mean

Standard Deviation

kilogram per square meter (kg/m^2)

Title

Denominators

Categories

Title	Measurements
	BG00027.14± 4.491 BG00127.73± 4.370

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Survival

Overall survival was calculated from the date of participant randomization to the date of participant death due to any cause. Participants without documentation of death at time of the analysis were censored as of the date the participant was last known to be alive, or the data cutoff date, whichever was earlier.

ITT population included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

Baseline until death (approximately up to 4.5 years)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants	OG000365 OG001734

Title

Denominators

Categories

Title	Measurements
	OG00015.3(13.48 to 16.86) OG00117.1(15.45 to 18.67)

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	Hazard ratio is based on a stratified Cox's proportional hazard regression model with stratification factors region (North America, Europe and Rest of World) and brief pain inventory-short form (BPI-SF) worst pain score at screening ([less than or equal to] <=4, greater than [>] 4) with treatment as a factor in the model. A hazard ratio less than 1 for the treatment indicates better prevention of the death in the Orteronel arm as compared to placebo arm.	Log Rank		0.12085		Hazard Ratio (HR)	0.875			2-Sided	95	0.739	1.036					Superiority or Other

Secondary

Radiographic Progression-free Survival (rPFS)

rPFS was defined as the time from randomization until radiographic disease progression or death due to any cause, whichever occurred first. Radiographic disease progression was defined as the occurrence of 1 or more of the following: The appearance of 2 or more new lesions on radionuclide bone scan as defined by prostate cancer working group (PCWG)2; Should 2 or more new bone lesions be evident at the first assessment (8-week assessment) on treatment, 2 or more additional new lesions must have been evident on a confirmatory assessment at least 6 weeks later; One or more new soft tissue/visceral organ lesions identified by computed tomography (CT)/magnetic resonance imaging (MRI); Progression as defined by response evaluation criteria in solid tumors (RECIST) 1.1 criteria.

ITT population included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Secondary

Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50 Response) at Week 12

The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50 percent (%) from baseline.

ITT population included all participants who were randomized.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants

Secondary

Percentage of Participants With Pain Response at Week 12

Pain response was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: A greater than or equal to (>=) 2 point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use; or a 25 percent (%) or more reduction in analgesic use from baseline without an increase in worst pain score from baseline.

ITT population included all participants who were randomized.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts

Secondary

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

Safety population included all participants who received at least 1 dose of any study drug.

Posted

Number

participants

Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Abnormal Physical Examination Findings

Safety population included all participants who received at least 1 dose of any study drug.

Posted

Number

participants

Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants	OG000

Secondary

Number of Participants With TEAEs Related to Vital Signs

Safety population included all participants who received at least 1 dose of any study drug.

Posted

Number

participants

Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants	OG000

Secondary

Number of Participants With TEAEs Related to Weight

Safety population included all participants who received at least 1 dose of any study drug.

Posted

Number

participants

Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status

ECOG assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Worst change was defined as the worst overall change that occurred in ECOG status at any measured time point during the treatment period.

Safety population where baseline and post-baseline assessments were available. Safety population included all participants who received at least 1 dose of any study drug.

Posted

Number

participants

Baseline up to End-of-treatment (EOT) (Cycle 59 Day 58)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Secondary

Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings

Safety population included all participants who received at least 1 dose of any study drug.

Posted

Number

participants

Cycle 59 Day 58

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants	OG000

Secondary

Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel

Safety population included all participants who received at least 1 dose of any study drug.

Posted

Number

participants

Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Achieving PSA50 Response at Any Time During the Study

The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50% from baseline.

ITT population where baseline and post-baseline assessments were available. The ITT population included all participants who were randomized.

Posted

Number

participants

Cycle: 4, 7, 10, 13, 16, 19, 22, and 25

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants

Secondary

Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12

The PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.

ITT population where baseline and post-baseline assessments were available. ITT population included all participants who were randomized.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants

Secondary

Percentage of Participants Achieving PSA90 Response at Any Time During the Study

The PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.

ITT population where baseline and post-baseline assessments were available. ITT population included all participants who were randomized.

Posted

Number

percentage of participants

Cycle: 7, 10, 13, 16, 19, 22, and 25

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants

Secondary

Best PSA Response at Any Time During the Study

The PSA50 was defined as the percentage of participants who had a PSA decline of at least 50% from baseline. PSA90 was defined as the percentage of participants who had a PSA decline of at least 90% from baseline.

Best PSA response was not evaluated due to change in planned analysis.

Posted

Cycle: 4, 7, 10, 13, 16, 19, 22, and 25

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants

Secondary

Time to PSA Progression

Time to PSA progression was defined as time from randomization to a PSA increase of 25% and PSA rise of at least 2 nanogram per milliliter (ng/mL) above the lowest value observed post baseline or, if no PSA decline occurred post baseline, above the baseline PSA.

ITT population included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

Baseline until the final on treatment assessment or until end of short term follow-up following discontinuation of treatment, whichever occurred later (approximately up to 4.5 years)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts

Secondary

Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC)

A favorable CTC count was defined as less than (<) 5 counts per (/) 7.5 mililiter (mL) in whole blood. An unfavorable CTC count was defined as >=5 counts/7.5 mL in whole blood.

ITT population where baseline and post-baseline assessments were available. ITT population included all participants who were randomized.

Posted

Number

participants

Baseline and EOT (Cycle 59 Day 58)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units	Counts
Participants

Secondary

Percentage of Participants With Objective Response

Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. The overall objective response was defined as a complete response (CR) or partial response (PR). A complete response (CR) was defined as the disappearance of all target lesions determined by computerized tomography (CT) or MRI. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 millimetre (mm). A PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of longest diameters of non-lymph node lesions and of the short diameter(s) or short axis of lymph nodes.

Response per RECIST-evaluable population was defined as a subset of participants who had measurable disease by RECIST 1.1 at baseline.

Posted

Number

percentage of participants

Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Secondary

Time to Pain Progression

Time to pain progression was defined as the time from participant randomization to the first assessment date of pain progression. Pain progression was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: The brief pain inventory-short form (BPI-SF) worst pain score was >= 4 with a >= 2 point increase over baseline in BPI-SF worst pain score with stable or increased analgesic use; The BPI-SF worst pain score was >= 4 but not less than baseline with new or increased (relative to baseline) Step II or Step III analgesic use; The BPI-SF worst pain score was <= 3 but not less than baseline with new or increased (relative to baseline) Step III analgesic use.

ITT population included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

Baseline until EOT visit or until end of short term follow-up, whichever occurred later (approximately up to 4.5 years)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Secondary

Time to Pain Response

Time to pain response was defined as the time from randomization until first pain response. Pain response was defined as the occurrence of 1 of the following and confirmed by an additional assessment, at least 3 weeks but not more than 5 weeks later: A >= 2 point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use, or a 25% or more reduction in analgesic use from baseline without an increase in worst pain score from baseline. The analysis was performed by Kaplan-Meier method.

ITT population included all participants who were randomized.

Posted

Median

95% Confidence Interval

months

Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Secondary

Number of Participants With Best Pain Response

Best pain response was evaluated in participants who had a pain response across the entire study were summarized by treatment group. The pain response was defined as a >=2-point reduction from baseline in BPI-SF worst pain score without an increase in analgesic use, or a 25% or more reduction in analgesic use from baseline without an increase in worst pain score from baseline.

ITT population included all participants who were randomized.

Posted

Number

participants

Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Units

Secondary

Percentage of Participants With Health-related Quality of Life (HRQOL) Response at Week 12

The global health status or quality of life (QOL) was measured as the HRQOL response rate at 12 weeks using the 2-item global health status index of the european organization for research and treatment of cancer-quality of life questionnaire-C30 (EORTC QLQ-C30) instrument. HRQOL response was defined as a 17-point increase from the baseline assessment on the QOL index, after the score had been linearly transformed to a 0 to 100 scale. EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional, and social), 1 global health status, 3 symptom scales (fatigue, pain, nausea/vomiting) and 6 single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score representing better level of functioning or greater degree of symptoms.

ITT population included all participants who were randomized.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.
OG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo + Prednisone	Orteronel placebo-matching tablets, orally, twice daily (BID) and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.			148	363	341	363
EG001	Orteronel + Prednisone	Orteronel 400 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study. In Japan only, participants were administered with orteronel 300 mg, tablets, orally, BID and prednisone 5 mg, tablets, orally, BID up to Day 28 of each treatment cycle throughout the study.			384	732	703	732

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Sepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG00114 affected732 at risk
Urosepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG00112 affected732 at risk
Septic shock	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG0017 affected732 at risk
Bacteraemia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Pneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0009 affected363 at risk EG00119 affected732 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0013 affected732 at risk
Lung infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Bronchopneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Lobar pneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG00120 affected732 at risk
Pyelonephritis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0014 affected732 at risk
Pyelonephritis acute	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pyelonephritis chronic	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Appendicitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Gastroenteritis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
Anal abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Abdominal infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Diverticulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Peritonitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Rectal abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cellulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0015 affected732 at risk
Pneumonia bacterial	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Bacterial infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Endocarditis bacterial	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Device related infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Respiratory tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pelvic abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Wound infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Herpes zoster	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Abscess oral	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Tooth abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Soft tissue infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Subcutaneous abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Erysipelas	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pneumonia pneumococcal	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Fungal oesophagitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Proteus infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Salmonella sepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Spinal cord infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Nosocomial infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Listeriosis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG00024 affected363 at risk EG00133 affected732 at risk
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG0016 affected732 at risk
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0005 affected363 at risk EG0019 affected732 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0015 affected732 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
Metastatic pulmonary embolism	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Lymphangiosis carcinomatosa	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Metastases to the mediastinum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Metastases to lymph nodes	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Bone marrow tumour cell infiltration	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0011 affected732 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Anal cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Chronic lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Metastatic renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0006 affected363 at risk EG00118 affected732 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG00113 affected732 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG00110 affected732 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0010 affected732 at risk
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG0016 affected732 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0015 affected732 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Ileus	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Subileus	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Colitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Gastritis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Gastroduodenitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0010 affected732 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Oesophageal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Retroperitoneal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Diverticulitis intestinal haemorrhagic	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
General physical health deterioration	General disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG00119 affected732 at risk
Multi-organ failure	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Disease progression	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Performance status decreased	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Fatigue	General disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG00110 affected732 at risk
Asthenia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG00110 affected732 at risk
Malaise	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0014 affected732 at risk
Pyrexia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0018 affected732 at risk
Pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0013 affected732 at risk
Chest pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
Non-cardiac chest pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Spinal pain	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Oedema peripheral	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Generalised oedema	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Death	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Sudden death	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Thrombosis in device	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Device occlusion	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Drug intolerance	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Gait disturbance	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Cyst	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG00112 affected732 at risk
Renal failure	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG00111 affected732 at risk
Postrenal failure	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Renal impairment	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0012 affected732 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Urinary retention	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG00114 affected732 at risk
Dysuria	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Urge incontinence	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Micturition urgency	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Haematuria	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG0019 affected732 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG0013 affected732 at risk
Obstructive uropathy	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Renal disorder	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
Azotaemia	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Calculus urethral	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG0010 affected732 at risk
Urinoma	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Bladder perforation	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Ureteric rupture	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Spinal cord compression	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0009 affected363 at risk EG00117 affected732 at risk
Cauda equina syndrome	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Nerve root compression	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Syncope	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0018 affected732 at risk
Lethargy	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0015 affected732 at risk
Presyncope	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0014 affected732 at risk
Paraparesis	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0014 affected732 at risk
Paraplegia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Intraventricular haemorrhage	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Central nervous system haemorrhage	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Vascular encephalopathy	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Vertebrobasilar insufficiency	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Ataxia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
VIIth nerve paralysis	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Sciatica	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cognitive disorder	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Parkinson's disease	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Tremor	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Seizure	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Neuralgia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG00120 affected732 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0018 affected732 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG0017 affected732 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Alveolitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG00110 affected732 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0011 affected732 at risk
Flank pain	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00014 affected363 at risk EG0018 affected732 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Pubic pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0017 affected732 at risk
Osteoporotic fracture	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0014 affected732 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG0013 affected732 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Chondrocalcinosis pyrophosphate	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Mobility decreased	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0010 affected732 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0015 affected732 at risk
Myocardial infarction	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0014 affected732 at risk
Angina unstable	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected363 at risk EG0019 affected732 at risk
Atrial flutter	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cardiac failure	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0015 affected732 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0014 affected732 at risk
Cardiac arrest	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Bradycardia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Tachycardia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Arrhythmia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Aortic valve stenosis	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG00115 affected732 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG00110 affected732 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG00110 affected732 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected363 at risk EG0014 affected732 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Lactic acidosis	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0009 affected363 at risk EG00121 affected732 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Thrombotic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
Anaemia of chronic disease	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Anaemia of malignant disease	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Haemolytic uraemic syndrome	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Lipase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG00112 affected732 at risk
Amylase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0015 affected732 at risk
Pancreatic enzymes increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0014 affected732 at risk
Liver function test abnormal	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Alanine aminotransferase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Blood creatinine increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0012 affected732 at risk
International normalised ratio increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Blood cortisol decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Blood glucose increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Weight decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Platelet count decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Haemoglobin decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Radiation proctitis	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Transfusion-related circulatory overload	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Kidney rupture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0010 affected732 at risk
Hypotension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Orthostatic hypotension	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Deep vein thrombosis	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0003 affected363 at risk EG0013 affected732 at risk
Haemorrhage	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Embolism	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Thrombosis	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Hypertension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Hypertensive crisis	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Lymphoedema	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Phlebitis	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Confusional state	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0014 affected732 at risk
Depression	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0012 affected732 at risk
Delusion	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Psychotic disorder	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Delirium	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0013 affected732 at risk
Mineralocorticoid deficiency	Endocrine disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Hyperthyroidism	Endocrine disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0013 affected732 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cholestasis	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Jaundice	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0011 affected732 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Bile duct stenosis	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Prostatomegaly	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk
Diplopia	Eye disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected363 at risk EG0010 affected732 at risk
Cor pulmonale	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected363 at risk EG0011 affected732 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG00059 affected363 at risk EG001103 affected732 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00094 affected363 at risk EG001319 affected732 at risk
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00060 affected363 at risk EG001272 affected732 at risk
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00064 affected363 at risk EG001222 affected732 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00054 affected363 at risk EG001201 affected732 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00021 affected363 at risk EG00146 affected732 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00013 affected363 at risk EG00146 affected732 at risk
Fatigue	General disorders	MedDRA (18.0)	Systematic Assessment	EG00084 affected363 at risk EG001223 affected732 at risk
Asthenia	General disorders	MedDRA (18.0)	Systematic Assessment	EG00039 affected363 at risk EG001102 affected732 at risk
Oedema peripheral	General disorders	MedDRA (18.0)	Systematic Assessment	EG00045 affected363 at risk EG00177 affected732 at risk
Pyrexia	General disorders	MedDRA (18.0)	Systematic Assessment	EG00018 affected363 at risk EG00148 affected732 at risk
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00024 affected363 at risk EG00157 affected732 at risk
Weight decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00034 affected363 at risk EG001113 affected732 at risk
Lipase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0005 affected363 at risk EG001113 affected732 at risk
Amylase increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0005 affected363 at risk EG001101 affected732 at risk
Blood creatinine increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0009 affected363 at risk EG00138 affected732 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00068 affected363 at risk EG001208 affected732 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00014 affected363 at risk EG00145 affected732 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00062 affected363 at risk EG001139 affected732 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00055 affected363 at risk EG001112 affected732 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00051 affected363 at risk EG00189 affected732 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00027 affected363 at risk EG001110 affected732 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00045 affected363 at risk EG00186 affected732 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00024 affected363 at risk EG00157 affected732 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00020 affected363 at risk EG00139 affected732 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00021 affected363 at risk EG00136 affected732 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00016 affected363 at risk EG00139 affected732 at risk
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00023 affected363 at risk EG00176 affected732 at risk
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00015 affected363 at risk EG00178 affected732 at risk
Insomnia	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG00026 affected363 at risk EG00167 affected732 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00021 affected363 at risk EG00167 affected732 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00019 affected363 at risk EG00163 affected732 at risk
Hypertension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG00022 affected363 at risk EG00184 affected732 at risk
Hot flush	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG00020 affected363 at risk EG00163 affected732 at risk

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

ID	Term
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds