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Study Comparing Orteronel Plus Prednisone in Participants With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT01193244
Recruitment Status : Completed
First Posted : September 1, 2010
Results First Posted : May 17, 2017
Last Update Posted : May 17, 2017
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: Orteronel
Drug: Placebo
Drug: Prednisone
Enrollment 1560
Recruitment Details Participants took part in the study at 324 investigative sites in North America, Europe, Australia, Brazil, Chile, Colombia, Hong Kong, Peru, Puerto Rico, Israel, Japan, Mexico, New Zealand, Singapore, South Africa, and Taiwan from 19 October 2010 to 7 April 2016.
Pre-assignment Details Male participants who were chemotherapy-naive and had metastatic castration-resistant prostate cancer (mCRPC) with documented progressive metastatic disease were enrolled in 1 of 2 treatment groups to receive Orteronel 400 milligram (mg) + Prednisone 5 mg or Placebo + Prednisone 5 mg.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Period Title: Overall Study
Started 779 781
Treated 770 [1] 784 [2]
Completed 391 391
Not Completed 388 390
Reason Not Completed
Withdrawal by Subject             79             97
Other             303             278
Lost to Follow-up             6             15
[1]
Participants who continued to receive Placebo after unblinding.
[2]
Participants randomized to receive Placebo but crossed-over to receive Orteronel after unblinding.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg Total
Hide Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Total of all reporting groups
Overall Number of Baseline Participants 779 781 1560
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 779 participants 781 participants 1560 participants
71.1  (8.19) 70.9  (8.26) 71.0  (8.22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 779 participants 781 participants 1560 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
779
 100.0%
781
 100.0%
1560
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 779 participants 781 participants 1560 participants
Hispanic or Latino
90
  11.6%
107
  13.7%
197
  12.6%
Not Hispanic or Latino
672
  86.3%
669
  85.7%
1341
  86.0%
Unknown or Not Reported
17
   2.2%
5
   0.6%
22
   1.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 779 participants 781 participants 1560 participants
American Indian or Alaska Native 10 12 22
Asian 51 38 89
Native Hawaiian or Other Pacific Islander 2 1 3
Black or African American 19 25 44
White 670 685 1355
Unknown or Not Reported 12 3 15
Other 15 17 32
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 779 participants 781 participants 1560 participants
Canada 22 22 44
United States 147 148 295
Austria 12 12 24
Belarus 6 10 16
Belgium 18 21 39
Bulgaria 6 6 12
Croatia 5 1 6
Czech Republic 13 18 31
Estonia 2 4 6
Finland 9 4 13
France 66 55 121
Germany 29 40 69
Greece 23 16 39
Hungary 3 4 7
Ireland 11 13 24
Italy 10 8 18
Latvia 12 14 26
Lithuania 19 18 37
Netherlands 35 38 73
Poland 0 4 4
Portugal 4 4 8
Romania 20 13 33
Slovakia 9 11 20
Spain 14 12 26
Sweden 11 6 17
Switzerland 10 8 18
Ukraine 25 23 48
United Kingdom 42 53 95
Australia 27 27 54
Brazil 41 50 91
Chile 20 20 40
Colombia 3 6 9
Hong Kong 1 3 4
Israel 14 4 18
Japan 22 18 40
Mexico 7 9 16
New Zealand 25 26 51
Peru 6 10 16
Puerto Rico 1 1 2
Singapore 5 2 7
South Africa 6 4 10
Taiwan, Province Of China 12 10 22
Russia 6 5 11
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Centimeter
Number Analyzed 779 participants 781 participants 1560 participants
172.77  (7.485) 173.26  (7.858) 173.02  (7.675)
[1]
Measure Description: Height data was available for 1558 participants as follows: n= 778, 780.
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 779 participants 781 participants 1560 participants
84.04  (15.846) 85.09  (16.286) 84.57  (16.071)
[1]
Measure Description: Weight data was available for 1559 participants as follows: n= 778, 781.
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 779 participants 781 participants 1560 participants
28.09  (4.651) 28.28  (4.730) 28.19  (4.690)
[1]
Measure Description: BMI data was available for 1557 participants as follows: n= 777, 780.
1.Primary Outcome
Title Radiographic Progression-free Survival (rPFS)
Hide Description rPFS was defined as the time from randomization to the first objective evidence of radiographic disease progression assessed by independent central radiology review or death due to any cause, whichever occurred first. Radiographic disease progression was evaluated by computerized tomography (CT) scan or magnetic resonance imaging (MRI) and radionuclide bone scans at regularly scheduled visits. Radiographic disease progression in bone required a confirmatory scan. Radiographic disease progression in soft tissue did not require a confirmatory scan for purposes of analysis. Radiographic disease progression was evaluated by independent central radiology review using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for soft tissue disease and Prostate Cancer Working Group (PCWG2) guidelines for bone disease. Participants who did not reach the endpoint were censored at their last assessment.
Time Frame Baseline until radiographic disease progression or death, whichever occurred first (approximately up to 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Median (95% Confidence Interval)
Unit of Measure: months
8.7
(8.32 to 10.91)
13.8
(13.05 to 14.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Hazard ratio is based on a stratified Cox’s proportional hazard regression model with stratification factors of region and radiographic disease progression at baseline with treatment as a factor in the model. A hazard ratio less than (<) 1 indicated better prevention of death in the orteronel group compared to the placebo group. From log-rank test stratified by region and radiographic disease progression at Baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.707
Confidence Interval 95%
0.626 to 0.799
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival
Hide Description 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.
Time Frame Baseline until death (up to 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Median (95% Confidence Interval)
Unit of Measure: months
29.5
(27.28 to 32.38)
29.9
(27.88 to 33.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Hazard ratio is based on a stratified Cox’s proportional hazard regression model with stratification factors of region and radiographic disease progression at baseline with treatment as a factor in the model. A hazard ratio <1 indicated better prevention of death in the orteronel group compared to the placebo group. From log-rank test stratified by region and radiographic disease progression at baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59755
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.963
Confidence Interval 95%
0.838 to 1.107
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50) Response at Week 12
Hide Description The PSA50 is defined as a decline of at least 50 percent (%) from baseline.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24.6
(21.7 to 27.8)
42.6
(39.1 to 46.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Logistic regression model with prognostic factors: region; radiographic disease progression at baseline; age; race; baseline Eastern Cooperative Oncology Group (ECOG) score; Gleason score at initial diagnosis; baseline PSA, natural log scale; presence of visceral disease; alkaline phosphatase; lactate dehydrogenase; and hemoglobin. Odds ratio greater than (>)1 favored orteronel. P-values tested for odds ratio equal to 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.166
Confidence Interval 95%
1.724 to 2.721
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Favorable Circulating Tumor Cell Count (CTC) Levels at Week 12
Hide Description A favorable CTC count was defined as less than <5 counts per 7.5 milliliter (mL) in whole blood. An unfavorable CTC count was defined as greater than or equal to (>=) 5 counts/7.5 mL in whole blood.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
9.1
(7.2 to 11.4)
15.4
(12.9 to 18.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Logistic regression model with prognostic factors: region; radiographic disease progression at baseline; age; race; baseline ECOG score; Gleason score at initial diagnosis; baseline PSA, natural log scale; presence of visceral disease; alkaline phosphatase; lactate dehydrogenase; and hemoglobin. Odds ratio > 1 favored orteronel. P-values tested for odds ratio equal to 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.712
Confidence Interval 95%
1.235 to 2.373
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Pain Progression
Hide Description 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. BPI-SF was an 11-item questionnaire, designed to assess severity and impact of pain on daily functions. Total score ranged from 0 to 100 with lower scores being indicative of less pain or pain interference.
Time Frame Baseline until End of treatment (EOT) (approximately up to 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(28.57 to NA)
[1]
Median was not estimable due to low number of events in the arm.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Prednisone 5 mg, Orteronel 400 mg + Prednisone 5 mg
Comments Hazard ratio is based on a stratified Cox’s proportional hazard regression model with stratification factors of region and radiographic disease progression at baseline with treatment as a factor in the model. A hazard ratio less than (<) 1 indicated better prevention of death in the orteronel group compared to the placebo group. From log-rank test stratified by region and radiographic disease progression at baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33906
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.885
Confidence Interval 95%
0.688 to 1.138
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 770 784
Measure Type: Number
Unit of Measure: participants
TEAE 733 769
Serious Adverse Events (SAE) 321 380
7.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events Greater Than or Equal to (>=) Grade 3
Hide Description Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE.
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 770 784
Measure Type: Number
Unit of Measure: participants
Grade 3 or higher TEAE 405 537
Grade 5 (Death) 78 77
8.Secondary Outcome
Title Number of Participants With TEAEs Related to Vital Signs
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 770 784
Measure Type: Number
Unit of Measure: participants
Hypertension 76 98
Pyrexia 26 41
Hypotension 12 26
9.Secondary Outcome
Title Number of Participants With TEAEs Related to Weight
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 770 784
Measure Type: Number
Unit of Measure: participants
Weight decreased 47 119
Weight increased 36 10
10.Secondary Outcome
Title Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
Hide Description 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 percent 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 percent 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.
Time Frame Baseline until EOT (approximately up to 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 760 771
Measure Type: Number
Unit of Measure: participants
Baseline: 0; Overall: 0 251 200
Baseline: 0; Overall: 1 177 237
Baseline: 0; Overall: 2 47 66
Baseline: 0; Overall: 3 22 15
Baseline: 0; Overall: 4 7 7
Baseline: 1; Overall: 0 6 6
Baseline: 1; Overall: 1 162 147
Baseline: 1; Overall: 2 57 60
Baseline: 1; Overall: 3 28 26
Baseline: 1; Overall: 4 2 6
Baseline: 2; Overall: 2 1 1
11.Secondary Outcome
Title Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings
Hide Description [Not Specified]
Time Frame Baseline up to EOT (Cycle 61 Day 58)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 770 784
Measure Type: Number
Unit of Measure: participants
130 163
12.Secondary Outcome
Title Worst Change From Baseline Over Time in Cardiac Ejection Fraction
Hide Description Worst change was defined as the worst overall change that occurred in cardiac ejection fraction at any measured time point.
Time Frame Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 676 670
Mean (Standard Deviation)
Unit of Measure: percent ejection fraction
-3.8  (6.93) -4.8  (7.00)
13.Secondary Outcome
Title Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Coagulation
Hide Description [Not Specified]
Time Frame Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 770 784
Measure Type: Number
Unit of Measure: participants
Investigations 215 399
Blood and lymphatic system disorders 114 107
Metabolism and nutrition disorders 204 336
14.Secondary Outcome
Title Percentage of Participants With Skeletal Related Events (SRE)
Hide Description Skeletal related (SRE) event is defined as a fracture or spinal cord compression or the need for radiation or surgery at the site of a prostate cancer metastatic lesion that is substantiated by radiographic or pathologic evidence.
Time Frame Baseline up to EOT (approximately up to 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.9
(8.8 to 13.3)
8.6
(6.7 to 10.8)
15.Secondary Outcome
Title Time to SRE
Hide Description Time to SRE is defined as the time from randomization to SRE, or death due to any cause, whichever comes first. SRE is defined as a fracture or spinal cord compression or the need for radiation or surgery at the site of a prostate cancer metastatic lesion that is substantiated by radiographic or pathologic evidence.
Time Frame Baseline up to EOT (Cycle 61 Day 58)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Median (95% Confidence Interval)
Unit of Measure: months
9.0
(8.32 to 10.98)
13.9
(13.68 to 16.57)
16.Secondary Outcome
Title Percentage of Participants Achieving PSA50 Response at Any Time During the Study
Hide Description The PSA50 is defined as a decline of PSA by 50 percent from baseline.
Time Frame Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population where baseline and post-baseline assessments were available. The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Cycle 4 (n= 687, 672)
28.09
(24.76 to 31.62)
49.70
(45.86 to 53.55)
Cycle 7 (n= 541, 540)
34.94
(30.92 to 39.12)
54.81
(50.51 to 59.07)
Cycle 10 (n= 438, 450)
36.99
(32.45 to 41.70)
56.00
(51.28 to 60.64)
Cycle 13 (n= 344, 382)
37.21
(32.09 to 42.56)
53.14
(48.00 to 58.24)
Cycle 16 (n= 286, 303)
34.27
(28.78 to 40.08)
54.13
(48.33 to 59.84)
Cycle 19 (n= 228, 272)
37.72
(31.41 to 44.36)
52.94
(46.82 to 59.00)
Cycle 22 (n= 184, 211)
33.15
(26.40 to 40.46)
54.03
(47.05 to 60.89)
Cycle 25 (n= 109, 119)
35.78
(26.83 to 45.53)
46.22
(37.04 to 55.59)
Cycle 28 (n= 67, 77)
44.78
(32.60 to 57.42)
48.05
(36.52 to 59.74)
Cycle 31 (n= 35, 39)
34.29
(19.13 to 52.21)
48.72
(32.42 to 65.22)
Cycle 34 (n= 22, 18)
36.36
(17.20 to 59.34)
38.89
(17.30 to 64.25)
Cycle 37 (n= 7, 5)
71.43
(29.04 to 96.33)
40.00
(5.27 to 85.34)
17.Secondary Outcome
Title Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12
Hide Description The PSA90 is defined as a decline of PSA by 90 percent from baseline.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Measure Type: Number
Unit of Measure: percentage of participants
5.4 16.7
18.Secondary Outcome
Title Percentage of Participants Achieving PSA90 Response at Any Time During the Study
Hide Description The PSA90 is defined as a decline of PSA by 90 percent from baseline.
Time Frame Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population where baseline and post-baseline assessments were available. The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Cycle 4 (n= 687, 672)
5.39
(3.82 to 7.35)
16.67
(13.93 to 19.70)
Cycle 7 (n= 541, 540)
8.69
(6.45 to 11.39)
22.22
(18.78 to 25.97)
Cycle 10 (n= 438, 450)
11.64
(8.79 to 15.02)
26.44
(22.42 to 30.78)
Cycle 13 (n= 344, 382)
12.79
(9.45 to 16.79)
26.18
(21.84 to 30.89)
Cycle 16 (n= 286, 303)
12.24
(8.67 to 16.61)
25.74
(20.91 to 31.05)
Cycle 19 (n= 228, 272)
12.72
(8.69 to 17.75)
26.10
(20.99 to 31.75)
Cycle 22 (n= 184, 211)
10.87
(6.77 to 16.29)
28.44
(22.45 to 35.03)
Cycle 25 (n= 109, 119)
11.01
(5.82 to 18.44)
21.01
(14.08 to 29.43)
Cycle 28 (n= 67, 77)
16.42
(8.49 to 27.48)
27.27
(17.74 to 38.62)
Cycle 31 (n= 35, 39)
8.57
(1.80 to 23.06)
12.82
(4.30 to 27.43)
Cycle 34 (n= 22, 18)
4.55
(0.12 to 22.84)
22.22
(6.41 to 47.64)
Cycle 37 (n= 7, 5)
14.29
(0.36 to 57.87)
20.00
(0.51 to 71.64)
19.Secondary Outcome
Title Time to PSA Progression
Hide Description Time to PSA progression was defined as time from randomization to a PSA increase of 25 percent 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, compared to baseline PSA.
Time Frame 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 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Median (95% Confidence Interval)
Unit of Measure: months
5.59
(5.56 to 5.59)
8.3
(8.28 to 8.35)
20.Secondary Outcome
Title Time to Docetaxel Chemotherapy
Hide Description Time to docetaxel based chemotherapy is defined as the time from randomization to the start of docetaxel based chemotherapy for prostate cancer, regardless of whether the participant received concurrent orteronel or not. Deaths due to disease progression prior to Docetaxel based chemotherapy were considered as events.
Time Frame Baseline until start of docetaxel chemotherapy (up to 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Median (95% Confidence Interval)
Unit of Measure: months
19.0
(16.44 to 21.43)
23.0
(20.71 to 24.65)
21.Secondary Outcome
Title Time to Subsequent Antineoplastic Therapy
Hide Description Time to subsequent antineoplastic therapy is defined as the time from randomization to the start of any alternate antineoplastic therapy for prostate cancer. Deaths due to disease progression prior to antineoplastic therapy for prostate cancer are considered as events. Otherwise, time to next therapy is censored at the date of death or the last date the participant was known to be alive or the data cutoff date, whichever is earlier.
Time Frame Baseline until start of subsequent antineoplastic therapy (up to 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Median (95% Confidence Interval)
Unit of Measure: months
13.9
(12.16 to 14.86)
17.2
(15.09 to 18.97)
22.Secondary Outcome
Title Percentage of Participants With Objective Response
Hide Description Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1. A 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 or short axis of lymph nodes.
Time Frame Baseline until disease progression or death, whichever occurred first (approximately up to 4.7 years)
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Hide Analysis Population Description
The Response Evaluation Criteria in Solid Tumors (RECIST) evaluable population included all participants who had measurable disease by RECIST 1.1 at the baseline assessment.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 243 236
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
15.2
(11.0 to 20.4)
34.7
(28.7 to 41.2)
23.Secondary Outcome
Title Time to Deterioration in Global Health Status
Hide Description Global health status deterioration is defined as a drop greater than 16 points from the baseline assessment, confirmed at least 3 weeks later, on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module 30 (EORTC QLQ-C30) index after the score has been linearly transformed to a 0 to 100 scale. EORTC QLQ-C30 consists of 30 questions, where question 1 to 28 can be answered with 1: Not at all, 2: A little, 3: Quite a bit, 4: Very much and question 29 to 30 with 1: Very poor to 7: Excellent. For subscales a high score from 0-100 indicates: high global quality of life, high level of functioning (physical, role, emotional, cognitive, social) or a high level of symptoms (fatigue, nausea, pain, dyspnea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties).
Time Frame Baseline until EOT (approximately up to 4.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were randomized.
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description:
Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
Overall Number of Participants Analyzed 779 781
Median (95% Confidence Interval)
Unit of Measure: months
10.7
(8.97 to 11.11)
8.3
(7.36 to 10.16)
Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (up to Cycle 61 Day 58).
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Hide Arm/Group Description Orteronel placebo-matching tablets, orally, twice daily (BID) and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. Orteronel 400 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study. In Japan, participants were administered with Orteronel 300 mg, tablets, orally, BID and Prednisone 5 mg, tablets, orally, BID for up to Day 28 of each treatment cycle throughout the study.
All-Cause Mortality
Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   321/770 (41.69%)   380/784 (48.47%) 
Blood and lymphatic system disorders     
Anaemia  1  18/770 (2.34%)  18/784 (2.30%) 
Normochromic normocytic anaemia  1  1/770 (0.13%)  0/784 (0.00%) 
Febrile neutropenia  1  2/770 (0.26%)  1/784 (0.13%) 
Neutropenia  1  1/770 (0.13%)  1/784 (0.13%) 
Pancytopenia  1  1/770 (0.13%)  1/784 (0.13%) 
Bone marrow failure  1  0/770 (0.00%)  1/784 (0.13%) 
Lymphadenopathy  1  0/770 (0.00%)  1/784 (0.13%) 
Thrombocytopenia  1  4/770 (0.52%)  0/784 (0.00%) 
Cardiac disorders     
Acute myocardial infarction  1  3/770 (0.39%)  7/784 (0.89%) 
Myocardial infarction  1  5/770 (0.65%)  5/784 (0.64%) 
Angina pectoris  1  4/770 (0.52%)  4/784 (0.51%) 
Angina unstable  1  2/770 (0.26%)  2/784 (0.26%) 
Acute coronary syndrome  1  1/770 (0.13%)  2/784 (0.26%) 
Myocardial ischaemia  1  2/770 (0.26%)  1/784 (0.13%) 
Stress cardiomyopathy  1  0/770 (0.00%)  1/784 (0.13%) 
Atrial fibrillation  1  18/770 (2.34%)  14/784 (1.79%) 
Atrial flutter  1  3/770 (0.39%)  3/784 (0.38%) 
Supraventricular tachycardia  1  0/770 (0.00%)  3/784 (0.38%) 
Atrial tachycardia  1  0/770 (0.00%)  2/784 (0.26%) 
Cardiac failure  1  7/770 (0.91%)  8/784 (1.02%) 
Cardiac failure acute  1  3/770 (0.39%)  2/784 (0.26%) 
Cardiac failure congestive  1  1/770 (0.13%)  2/784 (0.26%) 
Cardiogenic shock  1  0/770 (0.00%)  2/784 (0.26%) 
Cardiopulmonary failure  1  3/770 (0.39%)  1/784 (0.13%) 
Arrhythmia  1  0/770 (0.00%)  1/784 (0.13%) 
Bradycardia  1  0/770 (0.00%)  1/784 (0.13%) 
Extrasystoles  1  0/770 (0.00%)  1/784 (0.13%) 
Tachycardia  1  0/770 (0.00%)  1/784 (0.13%) 
Cardiac arrest  1  3/770 (0.39%)  2/784 (0.26%) 
Cardio-respiratory arrest  1  1/770 (0.13%)  1/784 (0.13%) 
Coronary artery disease  1  2/770 (0.26%)  2/784 (0.26%) 
Coronary artery stenosis  1  0/770 (0.00%)  1/784 (0.13%) 
Left ventricular dysfunction  1  0/770 (0.00%)  2/784 (0.26%) 
Cardiomegaly  1  0/770 (0.00%)  1/784 (0.13%) 
Ventricular hypertrophy  1  0/770 (0.00%)  1/784 (0.13%) 
Cardiotoxicity  1  0/770 (0.00%)  1/784 (0.13%) 
Intracardiac thrombus  1  1/770 (0.13%)  0/784 (0.00%) 
Mitral valve incompetence  1  0/770 (0.00%)  1/784 (0.13%) 
Pericardial effusion  1  0/770 (0.00%)  1/784 (0.13%) 
Atrioventricular block  1  1/770 (0.13%)  0/784 (0.00%) 
Conduction disorder  1  1/770 (0.13%)  0/784 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  2/770 (0.26%)  1/784 (0.13%) 
Allergy to arthropod sting  1  0/770 (0.00%)  1/784 (0.13%) 
Drug hypersensitivity  1  1/770 (0.13%)  0/784 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  0/770 (0.00%)  4/784 (0.51%) 
Adrenocortical insufficiency acute  1  0/770 (0.00%)  2/784 (0.26%) 
Secondary adrenocortical insufficiency  1  0/770 (0.00%)  1/784 (0.13%) 
Thyrotoxic crisis  1  0/770 (0.00%)  1/784 (0.13%) 
Eye disorders     
Cataract  1  2/770 (0.26%)  0/784 (0.00%) 
Optic ischaemic neuropathy  1  1/770 (0.13%)  0/784 (0.00%) 
Gastrointestinal disorders     
Vomiting  1  6/770 (0.78%)  9/784 (1.15%) 
Nausea  1  3/770 (0.39%)  9/784 (1.15%) 
Diarrhoea  1  5/770 (0.65%)  12/784 (1.53%) 
Abdominal pain  1  2/770 (0.26%)  8/784 (1.02%) 
Abdominal pain lower  1  0/770 (0.00%)  2/784 (0.26%) 
Pancreatitis acute  1  0/770 (0.00%)  5/784 (0.64%) 
Pancreatitis  1  0/770 (0.00%)  4/784 (0.51%) 
Pancreatitis relapsing  1  0/770 (0.00%)  1/784 (0.13%) 
Constipation  1  4/770 (0.52%)  7/784 (0.89%) 
Gastrointestinal hypomotility  1  0/770 (0.00%)  1/784 (0.13%) 
Gastrooesophageal reflux disease  1  1/770 (0.13%)  0/784 (0.00%) 
Ileus  1  0/770 (0.00%)  3/784 (0.38%) 
Intestinal obstruction  1  3/770 (0.39%)  1/784 (0.13%) 
Gallstone ileus  1  1/770 (0.13%)  0/784 (0.00%) 
Gastric ulcer  1  3/770 (0.39%)  1/784 (0.13%) 
Gastric ulcer perforation  1  1/770 (0.13%)  1/784 (0.13%) 
Gastric ulcer haemorrhage  1  0/770 (0.00%)  1/784 (0.13%) 
Mallory-Weiss syndrome  1  1/770 (0.13%)  2/784 (0.26%) 
Gastric haemorrhage  1  1/770 (0.13%)  1/784 (0.13%) 
Oesophageal varices haemorrhage  1  1/770 (0.13%)  0/784 (0.00%) 
Duodenal ulcer  1  1/770 (0.13%)  1/784 (0.13%) 
Duodenal ulcer haemorrhage  1  1/770 (0.13%)  1/784 (0.13%) 
Duodenal ulcer perforation  1  1/770 (0.13%)  0/784 (0.00%) 
Intestinal haemorrhage  1  0/770 (0.00%)  1/784 (0.13%) 
Rectal haemorrhage  1  0/770 (0.00%)  1/784 (0.13%) 
Large intestinal haemorrhage  1  1/770 (0.13%)  0/784 (0.00%) 
Food poisoning  1  0/770 (0.00%)  2/784 (0.26%) 
Duodenitis  1  0/770 (0.00%)  1/784 (0.13%) 
Enterocolitis  1  0/770 (0.00%)  1/784 (0.13%) 
Intestinal perforation  1  0/770 (0.00%)  1/784 (0.13%) 
Large intestine perforation  1  0/770 (0.00%)  1/784 (0.13%) 
Gastrointestinal haemorrhage  1  4/770 (0.52%)  1/784 (0.13%) 
Small intestinal obstruction  1  2/770 (0.26%)  1/784 (0.13%) 
Inguinal hernia  1  1/770 (0.13%)  1/784 (0.13%) 
Inguinal hernia, obstructive  1  1/770 (0.13%)  0/784 (0.00%) 
Anal stenosis  1  0/770 (0.00%)  1/784 (0.13%) 
Large intestine polyp  1  0/770 (0.00%)  1/784 (0.13%) 
Toothache  1  0/770 (0.00%)  1/784 (0.13%) 
Dysphagia  1  0/770 (0.00%)  1/784 (0.13%) 
Diverticular perforation  1  0/770 (0.00%)  1/784 (0.13%) 
Colitis ischaemic  1  1/770 (0.13%)  0/784 (0.00%) 
Pancreatic cyst  1  1/770 (0.13%)  0/784 (0.00%) 
Enterovesical fistula  1  1/770 (0.13%)  0/784 (0.00%) 
Haemorrhoids  1  1/770 (0.13%)  0/784 (0.00%) 
Oesophagitis ulcerative  1  1/770 (0.13%)  0/784 (0.00%) 
Proctitis  1  1/770 (0.13%)  0/784 (0.00%) 
General disorders     
Fatigue  1  2/770 (0.26%)  11/784 (1.40%) 
Asthenia  1  1/770 (0.13%)  3/784 (0.38%) 
Malaise  1  2/770 (0.26%)  2/784 (0.26%) 
General physical health deterioration  1  6/770 (0.78%)  9/784 (1.15%) 
Multi-organ failure  1  3/770 (0.39%)  3/784 (0.38%) 
Multi-organ disorder  1  1/770 (0.13%)  0/784 (0.00%) 
Performance status decreased  1  1/770 (0.13%)  0/784 (0.00%) 
Pyrexia  1  3/770 (0.39%)  6/784 (0.77%) 
Non-cardiac chest pain  1  1/770 (0.13%)  4/784 (0.51%) 
Discomfort  1  0/770 (0.00%)  1/784 (0.13%) 
Chest pain  1  2/770 (0.26%)  0/784 (0.00%) 
Oedema peripheral  1  1/770 (0.13%)  2/784 (0.26%) 
Face oedema  1  0/770 (0.00%)  1/784 (0.13%) 
Death  1  1/770 (0.13%)  0/784 (0.00%) 
Device occlusion  1  1/770 (0.13%)  0/784 (0.00%) 
Abasia  1  1/770 (0.13%)  0/784 (0.00%) 
Drug intolerance  1  1/770 (0.13%)  0/784 (0.00%) 
Hepatobiliary disorders     
Drug-induced liver injury  1  0/770 (0.00%)  3/784 (0.38%) 
Hepatitis toxic  1  0/770 (0.00%)  1/784 (0.13%) 
Cholecystitis  1  1/770 (0.13%)  1/784 (0.13%) 
Cholecystitis acute  1  2/770 (0.26%)  0/784 (0.00%) 
Cholelithiasis  1  1/770 (0.13%)  0/784 (0.00%) 
Hepatic failure  1  1/770 (0.13%)  0/784 (0.00%) 
Infections and infestations     
Pneumonia  1  9/770 (1.17%)  30/784 (3.83%) 
Lobar pneumonia  1  2/770 (0.26%)  2/784 (0.26%) 
Lower respiratory tract infection  1  1/770 (0.13%)  2/784 (0.26%) 
Bronchopneumonia  1  0/770 (0.00%)  2/784 (0.26%) 
Lung infection  1  2/770 (0.26%)  1/784 (0.13%) 
Bronchitis  1  1/770 (0.13%)  1/784 (0.13%) 
Sepsis  1  3/770 (0.39%)  12/784 (1.53%) 
Urosepsis  1  4/770 (0.52%)  6/784 (0.77%) 
Septic shock  1  2/770 (0.26%)  3/784 (0.38%) 
Bacteraemia  1  0/770 (0.00%)  1/784 (0.13%) 
Post procedural sepsis  1  0/770 (0.00%)  1/784 (0.13%) 
Pulmonary sepsis  1  0/770 (0.00%)  1/784 (0.13%) 
Urinary tract infection  1  9/770 (1.17%)  13/784 (1.66%) 
Pyelonephritis  1  2/770 (0.26%)  0/784 (0.00%) 
Gastroenteritis  1  4/770 (0.52%)  3/784 (0.38%) 
Appendicitis perforated  1  0/770 (0.00%)  2/784 (0.26%) 
Diverticulitis  1  0/770 (0.00%)  2/784 (0.26%) 
Diarrhoea infectious  1  0/770 (0.00%)  1/784 (0.13%) 
Gastrointestinal infection  1  0/770 (0.00%)  1/784 (0.13%) 
Cellulitis  1  2/770 (0.26%)  4/784 (0.51%) 
Arthritis bacterial  1  0/770 (0.00%)  1/784 (0.13%) 
Cellulitis gangrenous  1  0/770 (0.00%)  1/784 (0.13%) 
Cellulitis of male external genital organ  1  0/770 (0.00%)  1/784 (0.13%) 
Gangrene  1  0/770 (0.00%)  1/784 (0.13%) 
Pneumonia bacterial  1  0/770 (0.00%)  1/784 (0.13%) 
Urinary tract infection bacterial  1  0/770 (0.00%)  1/784 (0.13%) 
Infection  1  0/770 (0.00%)  2/784 (0.26%) 
Abscess limb  1  0/770 (0.00%)  1/784 (0.13%) 
Groin abscess  1  0/770 (0.00%)  1/784 (0.13%) 
Pelvic abscess  1  0/770 (0.00%)  1/784 (0.13%) 
Postoperative abscess  1  1/770 (0.13%)  0/784 (0.00%) 
Respiratory tract infection  1  1/770 (0.13%)  0/784 (0.00%) 
Erysipelas  1  2/770 (0.26%)  4/784 (0.51%) 
Pneumonia pneumococcal  1  0/770 (0.00%)  1/784 (0.13%) 
Herpes zoster  1  1/770 (0.13%)  4/784 (0.51%) 
Gastroenteritis viral  1  2/770 (0.26%)  2/784 (0.26%) 
Respiratory tract infection viral  1  0/770 (0.00%)  1/784 (0.13%) 
Osteomyelitis  1  0/770 (0.00%)  3/784 (0.38%) 
Intervertebral discitis  1  0/770 (0.00%)  1/784 (0.13%) 
Bursitis infective  1  1/770 (0.13%)  0/784 (0.00%) 
Abscess neck  1  0/770 (0.00%)  1/784 (0.13%) 
Muscle abscess  1  0/770 (0.00%)  1/784 (0.13%) 
Perineal abscess  1  1/770 (0.13%)  0/784 (0.00%) 
Diabetic foot infection  1  0/770 (0.00%)  1/784 (0.13%) 
Skin infection  1  0/770 (0.00%)  1/784 (0.13%) 
Pilonidal cyst  1  1/770 (0.13%)  0/784 (0.00%) 
Chronic sinusitis  1  0/770 (0.00%)  1/784 (0.13%) 
Upper respiratory tract infection  1  0/770 (0.00%)  1/784 (0.13%) 
Labyrinthitis  1  0/770 (0.00%)  1/784 (0.13%) 
Fungal oesophagitis  1  0/770 (0.00%)  1/784 (0.13%) 
Influenza  1  0/770 (0.00%)  1/784 (0.13%) 
Salmonellosis  1  0/770 (0.00%)  1/784 (0.13%) 
Borrelia infection  1  1/770 (0.13%)  0/784 (0.00%) 
Tongue abscess  1  1/770 (0.13%)  0/784 (0.00%) 
Escherichia urinary tract infection  1  1/770 (0.13%)  0/784 (0.00%) 
Klebsiella bacteraemia  1  1/770 (0.13%)  0/784 (0.00%) 
Staphylococcal infection  1  1/770 (0.13%)  0/784 (0.00%) 
Staphylococcal skin infection  1  1/770 (0.13%)  0/784 (0.00%) 
Tuberculosis  1  1/770 (0.13%)  0/784 (0.00%) 
Injury, poisoning and procedural complications     
Femoral neck fracture  1  0/770 (0.00%)  2/784 (0.26%) 
Hip fracture  1  2/770 (0.26%)  1/784 (0.13%) 
Humerus fracture  1  1/770 (0.13%)  1/784 (0.13%) 
Ankle fracture  1  0/770 (0.00%)  1/784 (0.13%) 
Fibula fracture  1  0/770 (0.00%)  1/784 (0.13%) 
Forearm fracture  1  0/770 (0.00%)  1/784 (0.13%) 
Hand fracture  1  0/770 (0.00%)  1/784 (0.13%) 
Patella fracture  1  0/770 (0.00%)  1/784 (0.13%) 
Radius fracture  1  0/770 (0.00%)  1/784 (0.13%) 
Tibia fracture  1  0/770 (0.00%)  1/784 (0.13%) 
Femur fracture  1  3/770 (0.39%)  0/784 (0.00%) 
Upper limb fracture  1  1/770 (0.13%)  0/784 (0.00%) 
Post procedural complication  1  0/770 (0.00%)  1/784 (0.13%) 
Post procedural fistula  1  0/770 (0.00%)  1/784 (0.13%) 
Procedural complication  1  0/770 (0.00%)  1/784 (0.13%) 
Post procedural haematoma  1  1/770 (0.13%)  0/784 (0.00%) 
Fall  1  6/770 (0.78%)  3/784 (0.38%) 
Skeletal injury  1  1/770 (0.13%)  0/784 (0.00%) 
Toxicity to various agents  1  1/770 (0.13%)  3/784 (0.38%) 
Spinal compression fracture  1  0/770 (0.00%)  2/784 (0.26%) 
Spinal fracture  1  2/770 (0.26%)  0/784 (0.00%) 
Thoracic vertebral fracture  1  1/770 (0.13%)  0/784 (0.00%) 
Radiation proctitis  1  0/770 (0.00%)  2/784 (0.26%) 
Cystitis radiation  1  1/770 (0.13%)  0/784 (0.00%) 
Contusion  1  1/770 (0.13%)  1/784 (0.13%) 
Subdural haematoma  1  0/770 (0.00%)  1/784 (0.13%) 
Fractured ischium  1  0/770 (0.00%)  1/784 (0.13%) 
Limb injury  1  0/770 (0.00%)  1/784 (0.13%) 
Rib fracture  1  0/770 (0.00%)  1/784 (0.13%) 
Multiple fractures  1  1/770 (0.13%)  0/784 (0.00%) 
Tendon injury  1  1/770 (0.13%)  0/784 (0.00%) 
Post procedural pulmonary embolism  1  1/770 (0.13%)  0/784 (0.00%) 
Urethral stricture postoperative  1  1/770 (0.13%)  0/784 (0.00%) 
Incisional hernia  1  0/770 (0.00%)  1/784 (0.13%) 
Investigations     
Lipase increased  1  5/770 (0.65%)  7/784 (0.89%) 
Amylase increased  1  2/770 (0.26%)  2/784 (0.26%) 
Pancreatic enzymes increased  1  0/770 (0.00%)  1/784 (0.13%) 
Aspartate aminotransferase increased  1  1/770 (0.13%)  2/784 (0.26%) 
Alanine aminotransferase increased  1  0/770 (0.00%)  2/784 (0.26%) 
Gamma-glutamyltransferase increased  1  0/770 (0.00%)  2/784 (0.26%) 
Hepatic enzyme increased  1  0/770 (0.00%)  2/784 (0.26%) 
Liver function test abnormal  1  1/770 (0.13%)  1/784 (0.13%) 
Transaminases increased  1  1/770 (0.13%)  1/784 (0.13%) 
Blood creatinine increased  1  0/770 (0.00%)  6/784 (0.77%) 
Ejection fraction decreased  1  1/770 (0.13%)  2/784 (0.26%) 
International normalised ratio increased  1  1/770 (0.13%)  2/784 (0.26%) 
Blood calcium increased  1  0/770 (0.00%)  1/784 (0.13%) 
Eastern Cooperative Oncology Group performance status worsened  1  1/770 (0.13%)  0/784 (0.00%) 
Neutrophil count decreased  1  1/770 (0.13%)  0/784 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  8/770 (1.04%)  11/784 (1.40%) 
Hypovolaemia  1  0/770 (0.00%)  1/784 (0.13%) 
Diabetes mellitus  1  2/770 (0.26%)  8/784 (1.02%) 
Diabetes mellitus inadequate control  1  0/770 (0.00%)  1/784 (0.13%) 
Hyperkalaemia  1  0/770 (0.00%)  5/784 (0.64%) 
Hypokalaemia  1  1/770 (0.13%)  1/784 (0.13%) 
Hypoglycaemia  1  0/770 (0.00%)  6/784 (0.77%) 
Decreased appetite  1  0/770 (0.00%)  4/784 (0.51%) 
Hypocalcaemia  1  0/770 (0.00%)  3/784 (0.38%) 
Hyperglycaemia  1  5/770 (0.65%)  2/784 (0.26%) 
Hyponatraemia  1  3/770 (0.39%)  2/784 (0.26%) 
Fluid overload  1  0/770 (0.00%)  2/784 (0.26%) 
Cachexia  1  2/770 (0.26%)  1/784 (0.13%) 
Failure to thrive  1  2/770 (0.26%)  0/784 (0.00%) 
Diabetic ketoacidosis  1  2/770 (0.26%)  0/784 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  8/770 (1.04%)  12/784 (1.53%) 
Musculoskeletal chest pain  1  1/770 (0.13%)  2/784 (0.26%) 
Pain in extremity  1  3/770 (0.39%)  1/784 (0.13%) 
Flank pain  1  1/770 (0.13%)  0/784 (0.00%) 
Bone pain  1  4/770 (0.52%)  6/784 (0.77%) 
Spinal pain  1  1/770 (0.13%)  0/784 (0.00%) 
Osteonecrosis of jaw  1  2/770 (0.26%)  5/784 (0.64%) 
Pathological fracture  1  8/770 (1.04%)  3/784 (0.38%) 
Arthralgia  1  2/770 (0.26%)  3/784 (0.38%) 
Osteoarthritis  1  4/770 (0.52%)  1/784 (0.13%) 
Intervertebral disc protrusion  1  1/770 (0.13%)  1/784 (0.13%) 
Bursitis  1  0/770 (0.00%)  1/784 (0.13%) 
Costochondritis  1  0/770 (0.00%)  1/784 (0.13%) 
Rhabdomyolysis  1  0/770 (0.00%)  1/784 (0.13%) 
Groin pain  1  0/770 (0.00%)  1/784 (0.13%) 
Spinal column stenosis  1  0/770 (0.00%)  1/784 (0.13%) 
Arthropathy  1  1/770 (0.13%)  0/784 (0.00%) 
Joint destruction  1  1/770 (0.13%)  0/784 (0.00%) 
Osteoporosis  1  1/770 (0.13%)  0/784 (0.00%) 
Muscle haemorrhage  1  1/770 (0.13%)  0/784 (0.00%) 
Muscular weakness  1  1/770 (0.13%)  0/784 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  1  25/770 (3.25%)  24/784 (3.06%) 
Prostate cancer metastatic  1  1/770 (0.13%)  4/784 (0.51%) 
Metastatic pain  1  7/770 (0.91%)  12/784 (1.53%) 
Cancer pain  1  4/770 (0.52%)  2/784 (0.26%) 
Oncologic complication  1  1/770 (0.13%)  0/784 (0.00%) 
Tumour pain  1  1/770 (0.13%)  0/784 (0.00%) 
Metastases to bone  1  2/770 (0.26%)  1/784 (0.13%) 
Metastases to central nervous system  1  2/770 (0.26%)  1/784 (0.13%) 
Metastases to biliary tract  1  0/770 (0.00%)  1/784 (0.13%) 
Metastases to bladder  1  0/770 (0.00%)  1/784 (0.13%) 
Metastases to liver  1  0/770 (0.00%)  1/784 (0.13%) 
Metastases to small intestine  1  0/770 (0.00%)  1/784 (0.13%) 
Lymphangiosis carcinomatosa  1  1/770 (0.13%)  0/784 (0.00%) 
Metastases to lymph nodes  1  1/770 (0.13%)  0/784 (0.00%) 
Metastases to rectum  1  1/770 (0.13%)  0/784 (0.00%) 
Metastases to urinary tract  1  1/770 (0.13%)  0/784 (0.00%) 
Bladder cancer  1  1/770 (0.13%)  2/784 (0.26%) 
Bladder cancer recurrent  1  0/770 (0.00%)  1/784 (0.13%) 
Bladder transitional cell carcinoma  1  2/770 (0.26%)  0/784 (0.00%) 
Paraneoplastic syndrome  1  3/770 (0.39%)  2/784 (0.26%) 
Squamous cell carcinoma of skin  1  0/770 (0.00%)  2/784 (0.26%) 
Adenocarcinoma of colon  1  0/770 (0.00%)  1/784 (0.13%) 
Colon cancer  1  1/770 (0.13%)  0/784 (0.00%) 
Colorectal adenocarcinoma  1  1/770 (0.13%)  0/784 (0.00%) 
Colorectal cancer  1  1/770 (0.13%)  0/784 (0.00%) 
Squamous cell carcinoma  1  1/770 (0.13%)  1/784 (0.13%) 
Lung adenocarcinoma  1  0/770 (0.00%)  1/784 (0.13%) 
Squamous cell carcinoma of lung  1  1/770 (0.13%)  0/784 (0.00%) 
Pituitary tumour benign  1  0/770 (0.00%)  1/784 (0.13%) 
Gallbladder adenocarcinoma  1  0/770 (0.00%)  1/784 (0.13%) 
Gastric cancer  1  0/770 (0.00%)  1/784 (0.13%) 
Chronic lymphocytic leukaemia  1  0/770 (0.00%)  1/784 (0.13%) 
Lip squamous cell carcinoma  1  0/770 (0.00%)  1/784 (0.13%) 
Pancreatic carcinoma  1  0/770 (0.00%)  1/784 (0.13%) 
Throat cancer  1  0/770 (0.00%)  1/784 (0.13%) 
Neuroendocrine carcinoma  1  1/770 (0.13%)  0/784 (0.00%) 
Hepatic cancer  1  1/770 (0.13%)  0/784 (0.00%) 
Fibromatosis  1  1/770 (0.13%)  0/784 (0.00%) 
Nervous system disorders     
Cerebrovascular accident  1  8/770 (1.04%)  5/784 (0.64%) 
Cerebral ischaemia  1  2/770 (0.26%)  1/784 (0.13%) 
Ischaemic stroke  1  2/770 (0.26%)  1/784 (0.13%) 
Ischaemic cerebral infarction  1  1/770 (0.13%)  1/784 (0.13%) 
Cerebral haemorrhage  1  0/770 (0.00%)  1/784 (0.13%) 
Haemorrhage intracranial  1  0/770 (0.00%)  1/784 (0.13%) 
Haemorrhagic stroke  1  0/770 (0.00%)  1/784 (0.13%) 
Cerebellar haemorrhage  1  1/770 (0.13%)  0/784 (0.00%) 
Cerebral infarction  1  1/770 (0.13%)  0/784 (0.00%) 
Intraventricular haemorrhage  1  1/770 (0.13%)  0/784 (0.00%) 
Syncope  1  5/770 (0.65%)  7/784 (0.89%) 
Somnolence  1  0/770 (0.00%)  2/784 (0.26%) 
Depressed level of consciousness  1  1/770 (0.13%)  1/784 (0.13%) 
Spinal cord compression  1  11/770 (1.43%)  6/784 (0.77%) 
Cauda equina syndrome  1  0/770 (0.00%)  1/784 (0.13%) 
Radicular pain  1  0/770 (0.00%)  1/784 (0.13%) 
Nerve root compression  1  1/770 (0.13%)  0/784 (0.00%) 
Dizziness  1  1/770 (0.13%)  2/784 (0.26%) 
Presyncope  1  0/770 (0.00%)  2/784 (0.26%) 
Paraplegia  1  1/770 (0.13%)  1/784 (0.13%) 
Hemiplegia  1  0/770 (0.00%)  1/784 (0.13%) 
Monoplegia  1  0/770 (0.00%)  1/784 (0.13%) 
Hemiparesis  1  1/770 (0.13%)  0/784 (0.00%) 
Seizure  1  0/770 (0.00%)  3/784 (0.38%) 
Transient ischaemic attack  1  2/770 (0.26%)  2/784 (0.26%) 
Polyneuropathy  1  0/770 (0.00%)  1/784 (0.13%) 
Carotid artery stenosis  1  0/770 (0.00%)  1/784 (0.13%) 
Nystagmus  1  0/770 (0.00%)  1/784 (0.13%) 
Headache  1  0/770 (0.00%)  1/784 (0.13%) 
Peroneal nerve palsy  1  0/770 (0.00%)  1/784 (0.13%) 
Hypoaesthesia  1  0/770 (0.00%)  1/784 (0.13%) 
Peripheral motor neuropathy  1  0/770 (0.00%)  1/784 (0.13%) 
Encephalopathy  1  2/770 (0.26%)  0/784 (0.00%) 
IIIrd nerve disorder  1  1/770 (0.13%)  0/784 (0.00%) 
VIth nerve paralysis  1  1/770 (0.13%)  0/784 (0.00%) 
Parkinson's disease  1  1/770 (0.13%)  0/784 (0.00%) 
Tremor  1  1/770 (0.13%)  0/784 (0.00%) 
Psychiatric disorders     
Delirium  1  0/770 (0.00%)  1/784 (0.13%) 
Confusional state  1  1/770 (0.13%)  0/784 (0.00%) 
Depression  1  1/770 (0.13%)  0/784 (0.00%) 
Mental status changes  1  1/770 (0.13%)  0/784 (0.00%) 
Mood disorder due to a general medical condition  1  1/770 (0.13%)  0/784 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  6/770 (0.78%)  9/784 (1.15%) 
Renal failure  1  3/770 (0.39%)  7/784 (0.89%) 
Renal impairment  1  0/770 (0.00%)  3/784 (0.38%) 
Postrenal failure  1  2/770 (0.26%)  2/784 (0.26%) 
Renal injury  1  1/770 (0.13%)  1/784 (0.13%) 
Chronic kidney disease  1  1/770 (0.13%)  0/784 (0.00%) 
Urinary retention  1  20/770 (2.60%)  13/784 (1.66%) 
Urinary hesitation  1  0/770 (0.00%)  1/784 (0.13%) 
Bladder tamponade  1  1/770 (0.13%)  0/784 (0.00%) 
Pollakiuria  1  1/770 (0.13%)  0/784 (0.00%) 
Haematuria  1  16/770 (2.08%)  8/784 (1.02%) 
Hydronephrosis  1  6/770 (0.78%)  5/784 (0.64%) 
Obstructive uropathy  1  2/770 (0.26%)  0/784 (0.00%) 
Urinary tract obstruction  1  3/770 (0.39%)  3/784 (0.38%) 
Ureteric stenosis  1  1/770 (0.13%)  1/784 (0.13%) 
Hydroureter  1  1/770 (0.13%)  0/784 (0.00%) 
Calculus ureteric  1  2/770 (0.26%)  1/784 (0.13%) 
Bladder outlet obstruction  1  0/770 (0.00%)  1/784 (0.13%) 
Urinary bladder rupture  1  1/770 (0.13%)  0/784 (0.00%) 
Nephrolithiasis  1  0/770 (0.00%)  1/784 (0.13%) 
Renal colic  1  0/770 (0.00%)  1/784 (0.13%) 
Cystitis noninfective  1  1/770 (0.13%)  0/784 (0.00%) 
Azotaemia  1  1/770 (0.13%)  0/784 (0.00%) 
Renal artery thrombosis  1  1/770 (0.13%)  0/784 (0.00%) 
Urethral stenosis  1  1/770 (0.13%)  0/784 (0.00%) 
Reproductive system and breast disorders     
Prostatic obstruction  1  1/770 (0.13%)  1/784 (0.13%) 
Prostatomegaly  1  1/770 (0.13%)  0/784 (0.00%) 
Pelvic pain  1  0/770 (0.00%)  1/784 (0.13%) 
Prostatitis  1  1/770 (0.13%)  0/784 (0.00%) 
Scrotal oedema  1  1/770 (0.13%)  0/784 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  23/770 (2.99%)  27/784 (3.44%) 
Dyspnoea  1  5/770 (0.65%)  7/784 (0.89%) 
Dyspnoea exertional  1  0/770 (0.00%)  2/784 (0.26%) 
Respiratory distress  1  0/770 (0.00%)  1/784 (0.13%) 
Interstitial lung disease  1  0/770 (0.00%)  2/784 (0.26%) 
Atelectasis  1  0/770 (0.00%)  1/784 (0.13%) 
Organising pneumonia  1  0/770 (0.00%)  1/784 (0.13%) 
Respiratory failure  1  3/770 (0.39%)  2/784 (0.26%) 
Acute respiratory failure  1  2/770 (0.26%)  1/784 (0.13%) 
Chronic obstructive pulmonary disease  1  2/770 (0.26%)  3/784 (0.38%) 
Wheezing  1  1/770 (0.13%)  0/784 (0.00%) 
Pulmonary oedema  1  1/770 (0.13%)  2/784 (0.26%) 
Acute respiratory distress syndrome  1  0/770 (0.00%)  1/784 (0.13%) 
Pleural effusion  1  1/770 (0.13%)  2/784 (0.26%) 
Haemothorax  1  1/770 (0.13%)  0/784 (0.00%) 
Pneumothorax  1  1/770 (0.13%)  0/784 (0.00%) 
Pneumonitis  1  0/770 (0.00%)  2/784 (0.26%) 
Pneumonia aspiration  1  1/770 (0.13%)  0/784 (0.00%) 
Hypoxia  1  0/770 (0.00%)  2/784 (0.26%) 
Epistaxis  1  1/770 (0.13%)  1/784 (0.13%) 
Lung disorder  1  1/770 (0.13%)  1/784 (0.13%) 
Pharyngeal pouch  1  0/770 (0.00%)  1/784 (0.13%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1  0/770 (0.00%)  1/784 (0.13%) 
Urticaria  1  0/770 (0.00%)  1/784 (0.13%) 
Vascular disorders     
Deep vein thrombosis  1  5/770 (0.65%)  9/784 (1.15%) 
Peripheral artery thrombosis  1  1/770 (0.13%)  0/784 (0.00%) 
Orthostatic hypotension  1  1/770 (0.13%)  3/784 (0.38%) 
Hypotension  1  1/770 (0.13%)  1/784 (0.13%) 
Hypertension  1  0/770 (0.00%)  4/784 (0.51%) 
Hypovolaemic shock  1  0/770 (0.00%)  2/784 (0.26%) 
Shock  1  0/770 (0.00%)  1/784 (0.13%) 
Peripheral ischaemia  1  0/770 (0.00%)  2/784 (0.26%) 
Femoral artery occlusion  1  1/770 (0.13%)  0/784 (0.00%) 
Flushing  1  0/770 (0.00%)  1/784 (0.13%) 
Peripheral vascular disorder  1  0/770 (0.00%)  1/784 (0.13%) 
Aortic stenosis  1  2/770 (0.26%)  1/784 (0.13%) 
Aortic aneurysm rupture  1  1/770 (0.13%)  1/784 (0.13%) 
Hypertensive crisis  1  0/770 (0.00%)  1/784 (0.13%) 
Haematoma  1  0/770 (0.00%)  1/784 (0.13%) 
Venous thrombosis  1  0/770 (0.00%)  1/784 (0.13%) 
Phlebitis  1  0/770 (0.00%)  1/784 (0.13%) 
Lymphoedema  1  1/770 (0.13%)  0/784 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Prednisone 5 mg Orteronel 400 mg + Prednisone 5 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   721/770 (93.64%)   757/784 (96.56%) 
Blood and lymphatic system disorders     
Anaemia  1  90/770 (11.69%)  75/784 (9.57%) 
Gastrointestinal disorders     
Nausea  1  130/770 (16.88%)  281/784 (35.84%) 
Constipation  1  129/770 (16.75%)  261/784 (33.29%) 
Diarrhoea  1  110/770 (14.29%)  221/784 (28.19%) 
Vomiting  1  115/770 (14.94%)  174/784 (22.19%) 
Abdominal pain  1  40/770 (5.19%)  72/784 (9.18%) 
Dyspepsia  1  33/770 (4.29%)  60/784 (7.65%) 
Abdominal pain upper  1  39/770 (5.06%)  51/784 (6.51%) 
General disorders     
Fatigue  1  173/770 (22.47%)  269/784 (34.31%) 
Asthenia  1  70/770 (9.09%)  106/784 (13.52%) 
Oedema peripheral  1  85/770 (11.04%)  86/784 (10.97%) 
Infections and infestations     
Urinary tract infection  1  60/770 (7.79%)  58/784 (7.40%) 
Injury, poisoning and procedural complications     
Fall  1  47/770 (6.10%)  57/784 (7.27%) 
Investigations     
Lipase increased  1  35/770 (4.55%)  179/784 (22.83%) 
Weight decreased  1  54/770 (7.01%)  124/784 (15.82%) 
Amylase increased  1  27/770 (3.51%)  146/784 (18.62%) 
Blood creatinine increased  1  21/770 (2.73%)  78/784 (9.95%) 
Alanine aminotransferase increased  1  14/770 (1.82%)  49/784 (6.25%) 
Metabolism and nutrition disorders     
Decreased appetite  1  86/770 (11.17%)  170/784 (21.68%) 
Diabetes mellitus  1  23/770 (2.99%)  45/784 (5.74%) 
Hyperkalaemia  1  15/770 (1.95%)  47/784 (5.99%) 
Dehydration  1  18/770 (2.34%)  42/784 (5.36%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  196/770 (25.45%)  158/784 (20.15%) 
Muscle spasms  1  118/770 (15.32%)  171/784 (21.81%) 
Arthralgia  1  122/770 (15.84%)  123/784 (15.69%) 
Pain in extremity  1  93/770 (12.08%)  79/784 (10.08%) 
Bone pain  1  75/770 (9.74%)  65/784 (8.29%) 
Musculoskeletal pain  1  64/770 (8.31%)  55/784 (7.02%) 
Musculoskeletal chest pain  1  42/770 (5.45%)  51/784 (6.51%) 
Muscular weakness  1  42/770 (5.45%)  42/784 (5.36%) 
Myalgia  1  39/770 (5.06%)  45/784 (5.74%) 
Nervous system disorders     
Dizziness  1  50/770 (6.49%)  105/784 (13.39%) 
Headache  1  50/770 (6.49%)  70/784 (8.93%) 
Dysgeusia  1  15/770 (1.95%)  46/784 (5.87%) 
Psychiatric disorders     
Insomnia  1  65/770 (8.44%)  84/784 (10.71%) 
Depression  1  23/770 (2.99%)  56/784 (7.14%) 
Renal and urinary disorders     
Haematuria  1  45/770 (5.84%)  43/784 (5.48%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  41/770 (5.32%)  84/784 (10.71%) 
Cough  1  58/770 (7.53%)  62/784 (7.91%) 
Dyspnoea exertional  1  22/770 (2.86%)  41/784 (5.23%) 
Vascular disorders     
Hypertension  1  80/770 (10.39%)  98/784 (12.50%) 
Hot flush  1  77/770 (10.00%)  81/784 (10.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.0)
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.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01193244     History of Changes
Other Study ID Numbers: C21004
2010-018661-35 ( EudraCT Number )
0991413276 ( Other Identifier: TCTIP )
10/H0406/75 ( Registry Identifier: NRES )
U1111-1181-0387 ( Registry Identifier: WHO )
First Submitted: August 31, 2010
First Posted: September 1, 2010
Results First Submitted: April 7, 2017
Results First Posted: May 17, 2017
Last Update Posted: May 17, 2017