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Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00887198
Recruitment Status : Completed
First Posted : April 23, 2009
Results First Posted : April 9, 2015
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: Abiraterone acetate
Drug: Placebo
Drug: Prednisone
Enrollment 1088
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo Placebo to AA
Hide Arm/Group Description Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression. Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression. Participants who were originally assigned to placebo were later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4*250 mg tablets) along with prednisone 5 mg tablet.
Period Title: Randomized Period
Started 546 542 0
Treated 542 540 0
Completed 0 0 0
Not Completed 546 542 0
Reason Not Completed
Ongoing             42             0             0
Adverse Event             50             33             0
Lost to Follow-up             1             0             0
Cross-over to AA (under amendment 3)             0             51             0
Withdrawal by Subject             41             56             0
Progressive disease             366             370             0
Other             42             30             0
Randomized, Not treated             4             2             0
Period Title: Cross Over (Placebo to AA)
Started 0 0 93 [1]
Completed 0 0 0
Not Completed 0 0 93
Reason Not Completed
Started other prostate cancer treatment             0             0             8
Ongoing             0             0             35
Adverse Event             0             0             9
Withdrawal by Subject             0             0             2
Progressive disease             0             0             20
Other             0             0             19
[1]
93= 51 participants(crossed over under amendment 3)+42 participants (crossed over under amendment 4)
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo Total
Hide Arm/Group Description Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression. Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression. Total of all reporting groups
Overall Number of Baseline Participants 546 542 1088
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 546 participants 542 participants 1088 participants
70.5  (8.8) 70.1  (8.72) 70.3  (8.76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 546 participants 542 participants 1088 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
546
 100.0%
542
 100.0%
1088
 100.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 546 participants 542 participants 1088 participants
Australia
60
  11.0%
72
  13.3%
132
  12.1%
Belgium
25
   4.6%
17
   3.1%
42
   3.9%
Canada
63
  11.5%
37
   6.8%
100
   9.2%
France
24
   4.4%
29
   5.4%
53
   4.9%
Germany
46
   8.4%
32
   5.9%
78
   7.2%
Greece
7
   1.3%
7
   1.3%
14
   1.3%
Italy
1
   0.2%
6
   1.1%
7
   0.6%
Netherlands
15
   2.7%
15
   2.8%
30
   2.8%
Spain
25
   4.6%
20
   3.7%
45
   4.1%
Sweden
4
   0.7%
13
   2.4%
17
   1.6%
United Kingdom
42
   7.7%
56
  10.3%
98
   9.0%
United States
234
  42.9%
238
  43.9%
472
  43.4%
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the time from randomization to date of death from any cause.
Time Frame From randomization (Day 1) up to end of study (Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 546 542
Median (95% Confidence Interval)
Unit of Measure: Months
34.66
(32.72 to 36.80)
30.29
(28.65 to 33.28)
2.Primary Outcome
Title Radiographic Progression-free Survival (rPFS)
Hide Description The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (>=) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from randomization and was confirmed by a second bone scan taken >=6 weeks later showing >=2 additional new lesions (a total of >=4 new lesions compared to baseline), b) the first bone scan with >=2 new lesions compared to baseline was observed in >=12 weeks from randomization and the new lesions were verified on the next bone scan >=6 weeks later (a total of >=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI); 3) death from any cause.
Time Frame From randomization (Day 1) up to first radiographic progression or cutoff date (Month 18)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 546 542
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(11.66 to NA)
8.28
(8.12 to 8.54)
[1]
Data was not estimable due to insufficient number of participants who had the event.
3.Secondary Outcome
Title Time to Opiate Use for Prostate Cancer Pain
Hide Description The time interval from the date of randomization to the date of opiate use for cancer pain. Participants who have no opiate use at the time of analysis were censored at the last known date of no opiate use for cancer pain. Participants with no assessment were censored at the date of randomization.
Time Frame From randomization (Day 1) up to first opiate use or end of study (Month 60)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 546 542
Median (95% Confidence Interval)
Unit of Measure: Months
33.38
(30.23 to 39.75)
23.39
(20.27 to 27.53)
4.Secondary Outcome
Title Time to Initiation of Cytotoxic Chemotherapy
Hide Description The time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer. Participants who had no cytotoxic chemotherapy administration at the time of analysis were censored at the last known date when no cytotoxic chemotherapy was administered. Participants with no assessment were censored at the date of randomization.
Time Frame From randomization (Day 1) up to initiation of cytotoxic chemotherapy or cutoff date (Month 18)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 546 542
Median (95% Confidence Interval)
Unit of Measure: Months
25.17 [1] 
(23.26 to NA)
16.82
(14.55 to 19.38)
[1]
Upper limit was not estimable due to insufficient number of participants who had the event.
5.Secondary Outcome
Title Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Score by >=1 Point
Hide Description The time interval from the date of randomization to the first date at which there was at least a 1 grade change (worsening) in the ECOG performance status grade. Participants who had no deterioration in ECOG performance status grade at the time of the analysis were censored at the last known date of no deterioration. ECOG is a 5-point scale, where 0=Fully active, 1=Ambulatory, carry out work of sedentary nature, 2=Ambulatory, capable of all self-care, 3=Capable of limited self-care, confined to bed or chair more than 50% of waking hours, 4=Completely disabled, no self-care, totally confined to bed or chair, 5=Dead. Participants with no assessment were censored at the date of randomization.
Time Frame From randomization (Day 1) up to first radiographic progression or cutoff date (Month 18)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 546 542
Median (95% Confidence Interval)
Unit of Measure: Months
12.29
(11.33 to 14.29)
10.87
(9.49 to 11.76)
6.Secondary Outcome
Title Time to Prostate-specific Antigen (PSA) Progression
Hide Description The time interval from the date of randomization to the date of PSA progression as defined in the protocol-specific prostate cancer Working Group 2 (PCWG2) criteria. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase from nadir and an absolute increase of 2 nanogram/milliliter ((ng/mL) or more, which is confirmed by a second value obtained in 3 or more weeks. Participants who had no PSA progression at the time of the analysis were censored at the last known date of no PSA progression. Participants with no on-study PSA assessment or no baseline PSA assessment were censored at the date of randomization.
Time Frame From randomization (Day 1) up to date of PSA progerssion or cutoff date (Month 18)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all the randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 546 542
Median (95% Confidence Interval)
Unit of Measure: Months
11.07
(8.51 to 11.24)
5.55
(5.39 to 5.59)
7.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events
Hide Description An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame From first dose of study drug up to 30 days after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants in the randomized population who received any study drug.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo Placebo to Abiraterone Acetate
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received initially placebo along with prednisone 5 mg tablet, orally, later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4*250 mg tablets) along with prednisone 5 mg tablet due to disease progression.
Overall Number of Participants Analyzed 542 540 93
Measure Type: Number
Unit of Measure: Participants
With Treatment-Emergent Adverse Events 541 524 93
With Treatment-Emergent Serious Adverse Events 208 148 39
8.Secondary Outcome
Title Mean Plasma Concentrations of Abiraterone
Hide Description [Not Specified]
Time Frame Up to Cycle 5, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not reported as non-compartmental analysis was not performed due to sparse sampling.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Maximum Plasma Concentrations of Abiraterone
Hide Description [Not Specified]
Time Frame Up to Cycle 5, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not reported as non-compartmental analysis was not performed due to sparse sampling.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to Time the Last Quantifiable Concentration of Abiraterone (AUC[0-infinity])
Hide Description The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Time Frame Up to Cycle 5, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not reported as non-compartmental analysis was not performed due to sparse sampling.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Elimination Half-Life (t1/2)
Hide Description The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time Frame Up to Cycle 5, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not reported as non-compartmental analysis was not performed due to sparse sampling.
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo
Hide Arm/Group Description:
Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From first dose of study drug up to 30 days after the last dose of study drug (Approximately 5 years)
Adverse Event Reporting Description Safety analysis set included all participants in the randomized population who received any study drug.
 
Arm/Group Title Abiraterone Acetate + Prednisone (AAP) Placebo Placebo to AA
Hide Arm/Group Description Participants received 1000 milligram (mg) abiraterone acetate tablets (as 4*250 mg tablets) orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression. Participants received placebo matched to abiraterone acetate tablets orally once daily along with prednisone 5 mg tablet orally twice daily, from Day 1, Cycle1 (each cycle consist of 28 days) up to radiographic progression of disease and/or unequivocal clinical progression. Participants who were originally assigned to placebo were later on switched to 1,000 milligram (mg) abiraterone acetate tablet (as 4*250 mg tablets) along with prednisone 5 mg tablet.
All-Cause Mortality
Abiraterone Acetate + Prednisone (AAP) Placebo Placebo to AA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Abiraterone Acetate + Prednisone (AAP) Placebo Placebo to AA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   215/542 (39.67%)   156/540 (28.89%)   40/93 (43.01%) 
Blood and lymphatic system disorders       
Anaemia * 1  8/542 (1.48%)  6/540 (1.11%)  1/93 (1.08%) 
Coagulopathy * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Leukocytosis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Lymphopenia * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Thrombocytopenia * 1  1/542 (0.18%)  1/540 (0.19%)  1/93 (1.08%) 
Disseminated Intravascular Coagulation * 1  1/542 (0.18%)  0/540 (0.00%)  1/93 (1.08%) 
Febrile Neutropenia * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Cardiac disorders       
Tachyarrhythmia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Acute Coronary Syndrome * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Acute Myocardial Infarction * 1  1/542 (0.18%)  0/540 (0.00%)  1/93 (1.08%) 
Angina Pectoris * 1  6/542 (1.11%)  1/540 (0.19%)  0/93 (0.00%) 
Atrial Fibrillation * 1  11/542 (2.03%)  8/540 (1.48%)  0/93 (0.00%) 
Atrioventricular Block * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Atrioventricular Block Second Degree * 1  1/542 (0.18%)  0/540 (0.00%)  1/93 (1.08%) 
Bifascicular Block * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Cardiac Arrest * 1  1/542 (0.18%)  2/540 (0.37%)  0/93 (0.00%) 
Cardiac Disorder * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Cardiac Failure * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Cardiac Failure Congestive * 1  3/542 (0.55%)  0/540 (0.00%)  0/93 (0.00%) 
Conduction Disorder * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Coronary Artery Disease * 1  4/542 (0.74%)  1/540 (0.19%)  0/93 (0.00%) 
Ischaemic Cardiomyopathy * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Myocardial Infarction * 1  4/542 (0.74%)  5/540 (0.93%)  2/93 (2.15%) 
Myocardial Ischaemia * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Supraventricular Tachyarrhythmia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Supraventricular Tachycardia * 1  2/542 (0.37%)  0/540 (0.00%)  1/93 (1.08%) 
Ear and labyrinth disorders       
Hypoacusis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Vertigo * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Endocrine disorders       
Adrenal Insufficiency * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Gastrointestinal disorders       
Colitis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Constipation * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Diarrhoea * 1  2/542 (0.37%)  0/540 (0.00%)  1/93 (1.08%) 
Dyspepsia * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Gastritis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Ileus * 1  2/542 (0.37%)  1/540 (0.19%)  0/93 (0.00%) 
Melaena * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Nausea * 1  2/542 (0.37%)  0/540 (0.00%)  1/93 (1.08%) 
Pancreatitis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Periodontitis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Peritonitis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Vomiting * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Abdominal Pain * 1  3/542 (0.55%)  5/540 (0.93%)  0/93 (0.00%) 
Abdominal Pain Lower * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Abdominal Pain Upper * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Diverticular Perforation * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Diverticulum Intestinal * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Diverticulum Intestinal Haemorrhagic * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Enterovesical Fistula * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Food Poisoning * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Gastric Ulcer * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Gastritis Erosive * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Gastrointestinal Haemorrhage * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Gastrointestinal Necrosis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Gastrooesophageal Reflux Disease * 1  2/542 (0.37%)  1/540 (0.19%)  0/93 (0.00%) 
Intestinal Ischaemia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Intestinal Obstruction * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Oesophageal Mass * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Pancreatic Disorder * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Pancreatitis Necrotising * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Small Intestinal Obstruction * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Upper Gastrointestinal Haemorrhage * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Varices Oesophageal * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
General disorders       
Asthenia * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Fatigue * 1  2/542 (0.37%)  0/540 (0.00%)  2/93 (2.15%) 
Malaise * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Pain * 1  0/542 (0.00%)  1/540 (0.19%)  1/93 (1.08%) 
Pyrexia * 1  3/542 (0.55%)  3/540 (0.56%)  0/93 (0.00%) 
Catheter Related Complication * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Chest Pain * 1  0/542 (0.00%)  1/540 (0.19%)  1/93 (1.08%) 
Death * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Disease Progression * 1  8/542 (1.48%)  4/540 (0.74%)  6/93 (6.45%) 
Gait Disturbance * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
General Physical Health Deterioration * 1  7/542 (1.29%)  2/540 (0.37%)  0/93 (0.00%) 
Hypothermia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Mucosal Inflammation * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Multi-Organ Failure * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Non-Cardiac Chest Pain * 1  1/542 (0.18%)  4/540 (0.74%)  1/93 (1.08%) 
Oedema Peripheral * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Performance Status Decreased * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Systemic Inflammatory Response Syndrome * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Hepatobiliary disorders       
Cholecystitis * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Cholelithiasis * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Jaundice * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Bile Duct Obstruction * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Infections and infestations       
Bacteraemia * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Bronchitis * 1  1/542 (0.18%)  2/540 (0.37%)  0/93 (0.00%) 
Bronchopneumonia * 1  0/542 (0.00%)  2/540 (0.37%)  0/93 (0.00%) 
Cellulitis * 1  2/542 (0.37%)  3/540 (0.56%)  2/93 (2.15%) 
Cystitis * 1  3/542 (0.55%)  0/540 (0.00%)  0/93 (0.00%) 
Gastroenteritis * 1  6/542 (1.11%)  1/540 (0.19%)  0/93 (0.00%) 
Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Influenza * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Osteomyelitis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Pneumonia * 1  10/542 (1.85%)  4/540 (0.74%)  1/93 (1.08%) 
Pyelonephritis * 1  3/542 (0.55%)  2/540 (0.37%)  1/93 (1.08%) 
Sepsis * 1  7/542 (1.29%)  2/540 (0.37%)  1/93 (1.08%) 
Sinusitis * 1  2/542 (0.37%)  1/540 (0.19%)  0/93 (0.00%) 
Tracheobronchitis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Urosepsis * 1  3/542 (0.55%)  2/540 (0.37%)  1/93 (1.08%) 
Anal Abscess * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Arthritis Bacterial * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Biliary Sepsis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Bursitis Infective * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Campylobacter Gastroenteritis * 1  1/542 (0.18%)  0/540 (0.00%)  1/93 (1.08%) 
Enterococcal Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Escherichia Urinary Tract Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Febrile Infection * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Gallbladder Abscess * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Gastroenteritis Salmonella * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Gastroenteritis Viral * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Gastrointestinal Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Gingival Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Herpes Zoster * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Infected Skin Ulcer * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Infective Exacerbation of Chronic Obstructive Airways Disease * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Lower Respiratory Tract Infection * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Lung Infection * 1  3/542 (0.55%)  0/540 (0.00%)  0/93 (0.00%) 
Necrotising Fasciitis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Parainfluenzae Virus Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Pneumonia Influenzal * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Pneumonia Staphylococcal * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Postoperative Wound Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Pseudomonal Bacteraemia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Respiratory Tract Infection * 1  3/542 (0.55%)  0/540 (0.00%)  0/93 (0.00%) 
Skin Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Staphylococcal Infection * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Urinary Tract Infection * 1  14/542 (2.58%)  4/540 (0.74%)  5/93 (5.38%) 
Urinary Tract Infection Bacterial * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Viral Infection * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Wound Infection * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Injury, poisoning and procedural complications       
Fall * 1  2/542 (0.37%)  2/540 (0.37%)  1/93 (1.08%) 
Animal Scratch * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Ankle Fracture * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Bladder Perforation * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Cataract Operation Complication * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Cystitis Radiation * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Device Dislocation * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Femoral Neck Fracture * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Femur Fracture * 1  2/542 (0.37%)  1/540 (0.19%)  0/93 (0.00%) 
Gastroenteritis Radiation * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Gastrointestinal Anastomotic Leak * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Implantable Defibrillator Malfunction * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Multiple Fractures * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Multiple Injuries * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Narcotic Intoxication * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Procedural Pain * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Pubic Rami Fracture * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Scapula Fracture * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Skeletal Injury * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Skin Laceration * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Skull Fracture * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Soft Tissue Injury * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Spinal Compression Fracture * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Spinal Fracture * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Stress Fracture * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Subdural Haematoma * 1  0/542 (0.00%)  2/540 (0.37%)  2/93 (2.15%) 
Subdural Haemorrhage * 1  0/542 (0.00%)  2/540 (0.37%)  0/93 (0.00%) 
Tendon Rupture * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Thoracic Vertebral Fracture * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Tibia Fracture * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Wrist Fracture * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Investigations       
Colonoscopy * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Alanine Aminotransferase Increased * 1  5/542 (0.92%)  1/540 (0.19%)  0/93 (0.00%) 
Aspartate Aminotransferase Increased * 1  3/542 (0.55%)  1/540 (0.19%)  0/93 (0.00%) 
Blood Creatinine Increased * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Blood Uric Acid Increased * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Electrocardiogram QT Prolonged * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Electrocardiogram St Segment Depression * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Lipase Increased * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Platelet Count Decreased * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Metabolism and nutrition disorders       
Anorexia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Dehydration * 1  6/542 (1.11%)  1/540 (0.19%)  0/93 (0.00%) 
Hyperuricaemia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Hypoalbuminaemia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Hypoglycaemia * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Hypokalaemia * 1  2/542 (0.37%)  1/540 (0.19%)  0/93 (0.00%) 
Hyponatraemia * 1  2/542 (0.37%)  1/540 (0.19%)  1/93 (1.08%) 
Failure to Thrive * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Fluid Retention * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  2/542 (0.37%)  4/540 (0.74%)  0/93 (0.00%) 
Arthritis * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Bursitis * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Osteitis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Osteoarthritis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Osteonecrosis * 1  2/542 (0.37%)  1/540 (0.19%)  0/93 (0.00%) 
Back Pain * 1  6/542 (1.11%)  4/540 (0.74%)  1/93 (1.08%) 
Bone Pain * 1  4/542 (0.74%)  5/540 (0.93%)  1/93 (1.08%) 
Flank Pain * 1  2/542 (0.37%)  1/540 (0.19%)  0/93 (0.00%) 
Groin Pain * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Jaw Cyst * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Joint Swelling * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Lumbar Spinal Stenosis * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Muscular Weakness * 1  1/542 (0.18%)  0/540 (0.00%)  1/93 (1.08%) 
Musculoskeletal Chest Pain * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Musculoskeletal Pain * 1  1/542 (0.18%)  2/540 (0.37%)  0/93 (0.00%) 
Pain in Extremity * 1  1/542 (0.18%)  1/540 (0.19%)  2/93 (2.15%) 
Pathological Fracture * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Rotator Cuff Syndrome * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Spinal Column Stenosis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
B-Cell Type Acute Leukaemia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Basal Cell Carcinoma * 1  1/542 (0.18%)  0/540 (0.00%)  1/93 (1.08%) 
Bladder Cancer * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Bladder Transitional Cell Carcinoma * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Cancer Pain * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Central Nervous System Lymphoma * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Chronic Lymphocytic Leukaemia * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Colon Adenoma * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Colon Cancer * 1  0/542 (0.00%)  2/540 (0.37%)  0/93 (0.00%) 
Colorectal Cancer * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Gastric Cancer * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Intestinal Adenocarcinoma * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Lung Adenocarcinoma * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Lung Neoplasm * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Lung Neoplasm Malignant * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Malignant Melanoma * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Malignant Neoplasm of Ampulla of Vater * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Metastases to Meninges * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Metastatic Pain * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Pancreatic Carcinoma * 1  2/542 (0.37%)  0/540 (0.00%)  1/93 (1.08%) 
Squamous Cell Carcinoma * 1  1/542 (0.18%)  0/540 (0.00%)  1/93 (1.08%) 
Urethral Cancer * 1  0/542 (0.00%)  1/540 (0.19%)  1/93 (1.08%) 
Nervous system disorders       
Convulsion * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Dizziness * 1  2/542 (0.37%)  1/540 (0.19%)  0/93 (0.00%) 
Epilepsy * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Monoparesis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Paraesthesia * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Paraparesis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Paraplegia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Presyncope * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Quadriparesis * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Sciatica * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Syncope * 1  6/542 (1.11%)  1/540 (0.19%)  0/93 (0.00%) 
VIth nerve paralysis * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Amyotrophic Lateral Sclerosis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Carotid Artery Stenosis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Cerebral Haemorrhage * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Cerebral Infarction * 1  0/542 (0.00%)  2/540 (0.37%)  0/93 (0.00%) 
Cerebral Ischaemia * 1  3/542 (0.55%)  0/540 (0.00%)  0/93 (0.00%) 
Cerebrovascular Accident * 1  6/542 (1.11%)  2/540 (0.37%)  0/93 (0.00%) 
Embolic Stroke * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Loss of Consciousness * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Memory Impairment * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Migraine with Aura * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Nerve Root Compression * 1  2/542 (0.37%)  0/540 (0.00%)  1/93 (1.08%) 
Neurological Symptom * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Spinal Cord Compression * 1  7/542 (1.29%)  4/540 (0.74%)  0/93 (0.00%) 
Syncope Vasovagal * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Transient Ischaemic Attack * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Psychiatric disorders       
Agitation * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Delirium * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Completed Suicide * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Confusional State * 1  1/542 (0.18%)  2/540 (0.37%)  0/93 (0.00%) 
Renal and urinary disorders       
Dysuria * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Haematuria * 1  11/542 (2.03%)  5/540 (0.93%)  3/93 (3.23%) 
Hydronephrosis * 1  2/542 (0.37%)  4/540 (0.74%)  0/93 (0.00%) 
Nephrolithiasis * 1  3/542 (0.55%)  0/540 (0.00%)  0/93 (0.00%) 
Pollakiuria * 1  3/542 (0.55%)  2/540 (0.37%)  0/93 (0.00%) 
Bladder Mass * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Bladder Obstruction * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Bladder Spasm * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Bladder Tamponade * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Calculus Bladder * 1  0/542 (0.00%)  0/540 (0.00%)  2/93 (2.15%) 
Calculus Ureteric * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Haemorrhage Urinary Tract * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Obstructive Uropathy * 1  0/542 (0.00%)  2/540 (0.37%)  0/93 (0.00%) 
Renal Colic * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Renal Failure * 1  1/542 (0.18%)  3/540 (0.56%)  0/93 (0.00%) 
Renal Failure Acute * 1  3/542 (0.55%)  2/540 (0.37%)  1/93 (1.08%) 
Renal Impairment * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Ureteric Obstruction * 1  2/542 (0.37%)  2/540 (0.37%)  0/93 (0.00%) 
Ureteric Stenosis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Urethral Obstruction * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Urethral Stenosis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Urinary Incontinence * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Urinary Retention * 1  6/542 (1.11%)  3/540 (0.56%)  1/93 (1.08%) 
Urinary Tract Obstruction * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Reproductive system and breast disorders       
Prostatomegaly * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Erectile Dysfunction * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Prostatic Haemorrhage * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Scrotal Pain * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea * 1  2/542 (0.37%)  5/540 (0.93%)  0/93 (0.00%) 
Hypoxia * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Pneumothorax * 1  3/542 (0.55%)  1/540 (0.19%)  0/93 (0.00%) 
Acute Pulmonary Oedema * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Chronic Obstructive Pulmonary Disease * 1  0/542 (0.00%)  2/540 (0.37%)  0/93 (0.00%) 
Lung Disorder * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Pleural Effusion * 1  1/542 (0.18%)  3/540 (0.56%)  0/93 (0.00%) 
Pneumonia Aspiration * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Pulmonary Embolism * 1  10/542 (1.85%)  12/540 (2.22%)  1/93 (1.08%) 
Respiratory Failure * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Tonsillar Cyst * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Skin and subcutaneous tissue disorders       
Lentigo * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Actinic Keratosis * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Skin Lesion * 1  0/542 (0.00%)  0/540 (0.00%)  1/93 (1.08%) 
Surgical and medical procedures       
Chemotherapy * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Pancreatectomy * 1  2/542 (0.37%)  0/540 (0.00%)  0/93 (0.00%) 
Aortic Valve Replacement * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Knee Arthroplasty * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Transurethral Prostatectomy * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Vascular disorders       
Hypertension * 1  1/542 (0.18%)  3/540 (0.56%)  0/93 (0.00%) 
Hypotension * 1  1/542 (0.18%)  1/540 (0.19%)  0/93 (0.00%) 
Thrombophlebitis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Thrombosis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Arterial Thrombosis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Deep Vein Thrombosis * 1  4/542 (0.74%)  2/540 (0.37%)  0/93 (0.00%) 
Embolism Venous * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Hypertensive Crisis * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Orthostatic Hypotension * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Peripheral Embolism * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
Peripheral Vascular Disorder * 1  1/542 (0.18%)  0/540 (0.00%)  0/93 (0.00%) 
Venous Thrombosis * 1  0/542 (0.00%)  1/540 (0.19%)  0/93 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 11.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Abiraterone Acetate + Prednisone (AAP) Placebo Placebo to AA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   530/542 (97.79%)   505/540 (93.52%)   86/93 (92.47%) 
Blood and lymphatic system disorders       
Anaemia * 1  59/542 (10.89%)  53/540 (9.81%)  12/93 (12.90%) 
Gastrointestinal disorders       
Constipation * 1  144/542 (26.57%)  112/540 (20.74%)  15/93 (16.13%) 
Diarrhoea * 1  135/542 (24.91%)  98/540 (18.15%)  13/93 (13.98%) 
Dyspepsia * 1  62/542 (11.44%)  28/540 (5.19%)  1/93 (1.08%) 
Nausea * 1  144/542 (26.57%)  127/540 (23.52%)  15/93 (16.13%) 
Vomiting * 1  86/542 (15.87%)  61/540 (11.30%)  12/93 (12.90%) 
Abdominal Pain * 1  49/542 (9.04%)  44/540 (8.15%)  5/93 (5.38%) 
General disorders       
Asthenia * 1  46/542 (8.49%)  46/540 (8.52%)  1/93 (1.08%) 
Fatigue * 1  243/542 (44.83%)  200/540 (37.04%)  27/93 (29.03%) 
Pyrexia * 1  54/542 (9.96%)  33/540 (6.11%)  5/93 (5.38%) 
Oedema Peripheral * 1  148/542 (27.31%)  119/540 (22.04%)  22/93 (23.66%) 
Infections and infestations       
Bronchitis * 1  34/542 (6.27%)  14/540 (2.59%)  0/93 (0.00%) 
Nasopharyngitis * 1  65/542 (11.99%)  46/540 (8.52%)  5/93 (5.38%) 
Sinusitis * 1  29/542 (5.35%)  5/540 (0.93%)  3/93 (3.23%) 
Lower Respiratory Tract Infection * 1  12/542 (2.21%)  13/540 (2.41%)  5/93 (5.38%) 
Upper Respiratory Tract Infection * 1  74/542 (13.65%)  43/540 (7.96%)  4/93 (4.30%) 
Urinary Tract Infection * 1  49/542 (9.04%)  40/540 (7.41%)  11/93 (11.83%) 
Injury, poisoning and procedural complications       
Contusion * 1  81/542 (14.94%)  49/540 (9.07%)  6/93 (6.45%) 
Fall * 1  47/542 (8.67%)  20/540 (3.70%)  12/93 (12.90%) 
Skin Laceration * 1  13/542 (2.40%)  15/540 (2.78%)  6/93 (6.45%) 
Investigations       
Alanine Aminotransferase Increased * 1  70/542 (12.92%)  26/540 (4.81%)  3/93 (3.23%) 
Aspartate Aminotransferase Increased * 1  63/542 (11.62%)  25/540 (4.63%)  4/93 (4.30%) 
Weight Decreased * 1  42/542 (7.75%)  27/540 (5.00%)  6/93 (6.45%) 
Weight Increased * 1  29/542 (5.35%)  40/540 (7.41%)  2/93 (2.15%) 
Metabolism and nutrition disorders       
Anorexia * 1  56/542 (10.33%)  40/540 (7.41%)  10/93 (10.75%) 
Hyperglycaemia * 1  52/542 (9.59%)  41/540 (7.59%)  6/93 (6.45%) 
Hypokalaemia * 1  99/542 (18.27%)  68/540 (12.59%)  9/93 (9.68%) 
Hyponatraemia * 1  14/542 (2.58%)  15/540 (2.78%)  5/93 (5.38%) 
Decreased Appetite * 1  28/542 (5.17%)  30/540 (5.56%)  0/93 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  172/542 (31.73%)  131/540 (24.26%)  19/93 (20.43%) 
Myalgia * 1  40/542 (7.38%)  32/540 (5.93%)  3/93 (3.23%) 
Back Pain * 1  199/542 (36.72%)  180/540 (33.33%)  26/93 (27.96%) 
Bone Pain * 1  144/542 (26.57%)  112/540 (20.74%)  14/93 (15.05%) 
Groin Pain * 1  41/542 (7.56%)  22/540 (4.07%)  0/93 (0.00%) 
Muscle Spasms * 1  78/542 (14.39%)  111/540 (20.56%)  2/93 (2.15%) 
Muscular Weakness * 1  35/542 (6.46%)  42/540 (7.78%)  5/93 (5.38%) 
Musculoskeletal Pain * 1  97/542 (17.90%)  77/540 (14.26%)  12/93 (12.90%) 
Neck Pain * 1  30/542 (5.54%)  17/540 (3.15%)  2/93 (2.15%) 
Pain in Extremity * 1  107/542 (19.74%)  89/540 (16.48%)  16/93 (17.20%) 
Nervous system disorders       
Dizziness * 1  81/542 (14.94%)  73/540 (13.52%)  7/93 (7.53%) 
Headache * 1  86/542 (15.87%)  66/540 (12.22%)  9/93 (9.68%) 
Neuropathy Peripheral * 1  12/542 (2.21%)  6/540 (1.11%)  7/93 (7.53%) 
Psychiatric disorders       
Anxiety * 1  30/542 (5.54%)  23/540 (4.26%)  4/93 (4.30%) 
Depression * 1  32/542 (5.90%)  19/540 (3.52%)  3/93 (3.23%) 
Insomnia * 1  82/542 (15.13%)  62/540 (11.48%)  5/93 (5.38%) 
Renal and urinary disorders       
Haematuria * 1  56/542 (10.33%)  32/540 (5.93%)  4/93 (4.30%) 
Nocturia * 1  38/542 (7.01%)  29/540 (5.37%)  0/93 (0.00%) 
Pollakiuria * 1  56/542 (10.33%)  55/540 (10.19%)  2/93 (2.15%) 
Urinary Incontinence * 1  37/542 (6.83%)  25/540 (4.63%)  0/93 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  106/542 (19.56%)  74/540 (13.70%)  11/93 (11.83%) 
Dyspnoea * 1  71/542 (13.10%)  52/540 (9.63%)  7/93 (7.53%) 
Skin and subcutaneous tissue disorders       
Rash * 1  49/542 (9.04%)  21/540 (3.89%)  1/93 (1.08%) 
Vascular disorders       
Hypertension * 1  129/542 (23.80%)  73/540 (13.52%)  6/93 (6.45%) 
Hot Flush * 1  124/542 (22.88%)  100/540 (18.52%)  6/93 (6.45%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 11.0
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.
A copy of the manuscript must be provided to the Sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: SENIOR DIRECTOR CLINICAL RESEARCH
Organization: Janssen R&D US
EMail: ClinicalTrialDisclosure@its.jnj.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00887198    
Other Study ID Numbers: CR016927
COU-AA-302 ( Other Identifier: Janssen Research & Development, LLC )
2008-008004-41 ( EudraCT Number )
First Submitted: April 18, 2009
First Posted: April 23, 2009
Results First Submitted: March 30, 2015
Results First Posted: April 9, 2015
Last Update Posted: June 25, 2018