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A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer (PREVAIL)

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: NCT01212991
Recruitment Status : Completed
First Posted : October 1, 2010
Results First Posted : October 16, 2014
Last Update Posted : March 17, 2020
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: Enzalutamide
Drug: Placebo
Enrollment 1717
Recruitment Details  
Pre-assignment Details Following the independent data monitoring committee's recommendation, a protocol amendment was implemented for double-blind phase to be proceeded to open-label phase, which allowed previously placebo treated participants who had not received commercial enzalutamide the opportunity, to receive open-label access to enzalutamide.
Arm/Group Title Enzalutamide Placebo Placebo Participants Crossover to Enzalutamide
Hide Arm/Group Description Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Participants received placebo, administered as four capsules, once per day by mouth. Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Period Title: Double-blind
Started 872 845 0
Safety Population 871 844 0
Completed 0 234 0
Not Completed 872 611 0
Reason Not Completed
Lost to Follow-up             8             4             0
Death             699             550             0
Withdrawal by Subject             16             19             0
Other             7             0             0
Sponsor decision             142             38             0
Period Title: Open-label
Started 0 0 [1] 234 [2]
Completed 0 0 0
Not Completed 0 0 234
Reason Not Completed
Death             0             0             166
Lost to Follow-up             0             0             5
Withdrawal by Subject             0             0             7
Sponsor decision             0             0             53
Other             0             0             3
[1]
participants were given the opportunity to receive open-label access to enzalutamide
[2]
previous placebo treated participants were given the opportunity to receive enzalutamide
Arm/Group Title Enzalutamide Placebo Total
Hide Arm/Group Description Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Participants received placebo, administered as four capsules, once per day by mouth. Total of all reporting groups
Overall Number of Baseline Participants 872 845 1717
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 872 participants 845 participants 1717 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
179
  20.5%
179
  21.2%
358
  20.9%
>=65 years
693
  79.5%
666
  78.8%
1359
  79.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 872 participants 845 participants 1717 participants
71.3  (8.51) 71.2  (8.42) 71.3  (8.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 872 participants 845 participants 1717 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
872
 100.0%
845
 100.0%
1717
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Count of participants
Number Analyzed 872 participants 845 participants 1717 participants
United States 127 120 247
Slovakia 13 14 27
Finland 18 15 33
Spain 44 37 81
Lithuania 8 6 14
Austria 9 9 18
Russian Federation 12 10 22
Israel 14 11 25
United Kingdom 78 75 153
Italy 15 15 30
France 85 90 175
Canada 91 88 179
Poland 21 18 39
Belgium 28 29 57
Singapore 5 4 9
Australia 116 116 232
Denmark 43 44 87
Netherlands 15 13 28
Germany 41 42 83
Japan 28 33 61
Sweden 21 18 39
Korea, Republic of 40 38 78
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time from randomization to death due to any cause. For patients who were alive at the time of the analysis data cutoff, overall survival was censored at the last date the patient was known to be alive or analysis data cutoff date, whichever was first. This included patients who were known to have died after the data analysis cutoff date. Patients with no post-baseline survival information were censored on the date of randomization.
Time Frame During study period (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - All patients randomly assigned to treatment.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Overall Number of Participants Analyzed 872 845
Median (95% Confidence Interval)
Unit of Measure: months
32.4 [1] 
(30.1 to NA)
30.2 [1] 
(28.0 to NA)
[1]
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A 2-stage group sequential method (Lan DeMets OBF) assigned the level of significance for the pre-specified interim overall survival analysis (p<0.015) based on overall 2-sided type I error rate of 0.049. Final results based upon interim analysis.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.706
Confidence Interval (2-Sided) 95%
0.596 to 0.837
Estimation Comments The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with <1 favoring enzalutamide.
2.Primary Outcome
Title Radiographic Progression-free Survival (rPFS)
Hide Description Radiographic progression-free survival 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 within 168 days after treatment discontinuation, whichever was first. Radiographic disease progression was evaluated by CT scan or 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 RECIST 1.1 for soft tissue disease and PCWG2 guidelines for bone disease. Patients who did not reach the endpoint were censored at their last assessment.
Time Frame During study period (up to 20 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - All patients randomly assigned to treatment excluding 84 patients who were not randomized before the radiographic Progression-free Survival data cutoff date of 06 May 2012.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Overall Number of Participants Analyzed 832 801
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(13.8 to NA)
3.9
(3.7 to 5.4)
[1]
The median time to radiographic progression-free survival and its upper 95% confidence limit were not yet reached in the enzalutamide group because an insufficient number of patients had an event at the time of analysis.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The assigned 2-sided type I error rate was 0.001 for the analysis of radiographic progression-free survival.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.186
Confidence Interval (2-Sided) 95%
0.149 to 0.231
Estimation Comments The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.
3.Secondary Outcome
Title Time to First Skeletal-related Event
Hide Description Time to first skeletal-related event was defined as the time from randomization to the date of the first occurrence of a skeletal-related event for each patient. A skeletal-related event was defined as radiation therapy or surgery to bone for prostate cancer, pathological bone fracture, spinal cord compression, or initiation/change in antineoplastic therapy to treat bone pain from prostate cancer. Skeletal-related events were recorded at each scheduled and unscheduled study visit and during long-term follow-up if a skeletal-related event was not documented previously. Patients who did not have a skeletal-related event at the time of the analysis data cutoff were censored at the date of last assessment indicating no evidence of skeletal-related event. Patients with no postbaseline assessments were censored on the date of randomization.
Time Frame During study period (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - All patients randomly assigned to treatment.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Overall Number of Participants Analyzed 872 845
Median (95% Confidence Interval)
Unit of Measure: months
31.1 [1] 
(29.5 to NA)
31.3 [1] 
(23.9 to NA)
[1]
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.01 for this analysis.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.718
Confidence Interval 95%
0.610 to 0.844
Estimation Comments The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.
4.Secondary Outcome
Title Time to Initiation of Cytotoxic Chemotherapy
Hide Description The time to initiation of cytotoxic chemotherapy is defined as the time from randomization to the date of initiation of cytotoxic chemotherapy for the treatment of prostate cancer for each patient. For patients who did not start cytotoxic chemotherapy at the time of the analysis data cutoff, time to initiation of cytotoxic chemotherapy was censored at the date of last assessment where no cytotoxic chemotherapy was indicated or at the analysis data cutoff date, whichever was first. Time to initiation of cytotoxic chemotherapy for patients with no postbaseline assessments was censored on the date of randomization.
Time Frame During study period (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - All patients randomly assigned to treatment.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Overall Number of Participants Analyzed 872 845
Median (95% Confidence Interval)
Unit of Measure: months
28.0 [1] 
(25.8 to NA)
10.8
(9.7 to 12.2)
[1]
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.0125 for this analysis.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.349
Confidence Interval 95%
0.303 to 0.403
Estimation Comments The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.
5.Secondary Outcome
Title Time to Prostate-specific Antigen (PSA) Progression
Hide Description Time to PSA progression was defined as the time from randomization to date of first confirmed observation of PSA progression for each patient. For patients with PSA declines at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir was documented, and confirmed 3 or more weeks later. For patients with no PSA decline at week 13, the PSA progression date was defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above baseline was documented, and confirmed 3 or more weeks later. For patients who did not have confirmed PSA progression at the time of the analysis data cutoff, time to PSA progression was censored at the date of the last PSA assessment showing no evidence of confirmed PSA progression or the analysis data cutoff date, whichever was first. Time to PSA progression for patients with no postbaseline assessments was censored on the date of randomization.
Time Frame During study period (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) - All patients randomized.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Overall Number of Participants Analyzed 872 845
Median (95% Confidence Interval)
Unit of Measure: months
11.2
(11.1 to 13.7)
2.8
(2.8 to 2.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.0167 for this analysis.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.169
Confidence Interval 95%
0.147 to 0.195
Estimation Comments The hazard ratio is based on an unstratified Cox regression model (with treatment as the only covariate) and is relative to placebo with < 1 favoring enzalutamide.
6.Secondary Outcome
Title Percentage of Patients With Prostate Specific Antigen (PSA) Response ≥ 50%
Hide Description PSA response was defined as a ≥ 50% reduction in PSA from baseline to the lowest postbaseline PSA value and required confirmation by a consecutive assessment at least 3 weeks later. Patients were evaluable for PSA response rate if a patient had a PSA level measured at baseline and at least one postbaseline assessment.
Time Frame During study period (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable intent to treat (ITT) population - All patients randomly assigned to treatment with PSA values at baseline and at least one postbaseline assessment.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Overall Number of Participants Analyzed 854 777
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
78
(75.1 to 80.7)
3.5
(2.3 to 5.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.025 for this analysis.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in response rates
Estimated Value 74.51
Confidence Interval 95%
71.45 to 77.57
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Best Overall Soft Tissue Response
Hide Description The best overall soft tissue objective response is defined as partial response [PR] or complete response [CR] while on study treatment based on investigator assessments of target, nontarget, and new lesions using RECIST 1.1. Soft tissue was assessed by CT or MRI at regularly scheduled visits. Only patients with measurable soft tissue disease (ie, at least 1 target lesion identified per RECIST 1.1) at screening are included in this analysis. All percentages are based on number of participants with measurable soft tissue disease at screening in each treatment group.
Time Frame During study period (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population With Measurable Disease - All participants who were randomly assigned to treatment and had at least one target lesion at screening.
Arm/Group Title Enzalutamide Placebo
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Overall Number of Participants Analyzed 396 381
Measure Type: Number
Unit of Measure: Percentage of participants
58.8 5.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Enzalutamide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Holm step down method of multiple comparisons was used to maintain a study wide type I error of 5% for prespecified secondary efficacy analyses. The 2-sided type I error rate was 0.05 for this analysis.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in objective response rate
Estimated Value 53.85
Confidence Interval 95%
48.53 to 59.17
Estimation Comments [Not Specified]
8.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 first dose of study drug and up to a maximum of 6.5 years that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.
Time Frame Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all randomized participants who received at least 1 dose or partial dose of study drug.
Arm/Group Title Enzalutamide Placebo Placebo Participants Crossover to Enzalutamide
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Overall Number of Participants Analyzed 871 844 234
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
857
  98.4%
791
  93.7%
212
  90.6%
SAEs
384
  44.1%
229
  27.1%
104
  44.4%
9.Other Pre-specified Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute Common Terminology Criteria for AEs (CTCAE), Version 4.0
Hide Description An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. A treatment-emergent AE (TEAE) was defined as an AE that occurred from the date and time of the first dose of study drug up to a maximum duration of 6.5 years. Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported.
Time Frame Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all randomized participants who received at least 1 dose or partial dose of study drug.
Arm/Group Title Enzalutamide Placebo Placebo Participants Crossover to Enzalutamide
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Overall Number of Participants Analyzed 871 844 234
Measure Type: Count of Participants
Unit of Measure: Participants
465
  53.4%
318
  37.7%
129
  55.1%
10.Other Pre-specified Outcome
Title Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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 first dose of study drug and up to a maximum duration of 6.5 years that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
Time Frame Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all randomized participants who received at least 1 dose or partial dose of study drug.
Arm/Group Title Enzalutamide Placebo Placebo Participants Crossover to Enzalutamide
Hide Arm/Group Description:
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Participants received placebo, administered as four capsules, once per day by mouth.
Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
Overall Number of Participants Analyzed 871 844 234
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
579
  66.5%
423
  50.1%
119
  50.9%
SAEs
38
   4.4%
22
   2.6%
14
   6.0%
Time Frame Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 6.5 years)
Adverse Event Reporting Description Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety set.
 
Arm/Group Title Enzalutamide Placebo Placebo Participants Crossover to Enzalutamide
Hide Arm/Group Description Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Participants received placebo, administered as four capsules, once per day by mouth. Participants who received placebo in double-blind period and who agreed to proceed to open-label phase period, received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth.
All-Cause Mortality
Enzalutamide Placebo Placebo Participants Crossover to Enzalutamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   699/871 (80.25%)   550/844 (65.17%)   166/234 (70.94%) 
Hide Serious Adverse Events
Enzalutamide Placebo Placebo Participants Crossover to Enzalutamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   384/871 (44.09%)   229/844 (27.13%)   104/234 (44.44%) 
Blood and lymphatic system disorders       
Anaemia * 1  18/871 (2.07%)  9/844 (1.07%)  6/234 (2.56%) 
Disseminated intravascular coagulation * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Iron deficiency anaemia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Neutropenia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Pancytopenia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Haemolytic Uraemic Syndrome * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Idiopathic Thrombocytopenic Purpura * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Lymphadenopathy * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Platelet Dysfunction * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Cardiac disorders       
Atrial fibrillation * 1  10/871 (1.15%)  6/844 (0.71%)  0/234 (0.00%) 
Acute myocardial infarction * 1  11/871 (1.26%)  0/844 (0.00%)  1/234 (0.43%) 
Arteriosclerosis coronary artery * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Atrioventricular block * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Acute coronary syndrome * 1  5/871 (0.57%)  0/844 (0.00%)  0/234 (0.00%) 
Angina pectoris * 1  3/871 (0.34%)  0/844 (0.00%)  1/234 (0.43%) 
Angina unstable * 1  0/871 (0.00%)  1/844 (0.12%)  1/234 (0.43%) 
Cardiac failure acute * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Congestive cardiomyopathy * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Hypertensive heart disease * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Sick sinus syndrome * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Sinus tachycardia * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Ventricular tachycardia * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Ventricular extrasystoles * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Atrial Flutter * 1  0/871 (0.00%)  0/844 (0.00%)  2/234 (0.85%) 
Atrial Tachycardia * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Atrioventricular Block Complete * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Bradycardia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Cardiac Arrest * 1  3/871 (0.34%)  2/844 (0.24%)  0/234 (0.00%) 
Cardiac Failure * 1  5/871 (0.57%)  2/844 (0.24%)  3/234 (1.28%) 
Cardiac Failure Congestive * 1  2/871 (0.23%)  1/844 (0.12%)  1/234 (0.43%) 
Cardiopulmonary Failure * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Cardiovascular Insufficiency * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Coronary Artery Disease * 1  6/871 (0.69%)  0/844 (0.00%)  0/234 (0.00%) 
Coronary Artery Stenosis * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Ischaemic Cardiomyopathy * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Left Ventricular Failure * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Mitral Valve Disease * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Mitral Valve Incompetence * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Myocardial Infarction * 1  6/871 (0.69%)  1/844 (0.12%)  1/234 (0.43%) 
Supraventricular Tachycardia * 1  2/871 (0.23%)  0/844 (0.00%)  1/234 (0.43%) 
Tricuspid Valve Incompetence * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Ventricular Fibrillation * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Wolff-Parkinson-White Syndrome * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Ear and labyrinth disorders       
Vertigo * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Endocrine disorders       
Adrenal insufficiency * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Goitre * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Inappropriate antidiuretic hormone secretion * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Eye disorders       
Amaurosis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Cataract * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Retinal artery occlusion * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Eyelid Ptosis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Retinal Vein Occlusion * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Gastrointestinal disorders       
Constipation * 1  5/871 (0.57%)  5/844 (0.59%)  2/234 (0.85%) 
Vomiting * 1  2/871 (0.23%)  2/844 (0.24%)  0/234 (0.00%) 
Diarrhoea * 1  3/871 (0.34%)  1/844 (0.12%)  1/234 (0.43%) 
Nausea * 1  3/871 (0.34%)  0/844 (0.00%)  2/234 (0.85%) 
Upper gastrointestinal haemorrhage * 1  4/871 (0.46%)  0/844 (0.00%)  0/234 (0.00%) 
Abdominal pain * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Gastrointestinal haemorrhage * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Inguinal hernia * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Intestinal obstruction * 1  0/871 (0.00%)  2/844 (0.24%)  0/234 (0.00%) 
Melaena * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Small intestinal obstruction * 1  2/871 (0.23%)  1/844 (0.12%)  1/234 (0.43%) 
Duodenal ulcer haemorrhage * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Abdominal pain lower * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Diverticulum intestinal haemorrhagic * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Dysphagia * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Gastric ulcer haemorrhage * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Large intestinal haemorrhage * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Large intestine polyp * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Lower gastrointestinal haemorrhage * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Pancreatitis acute * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Peritoneal haemorrhage * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Rectal stenosis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Subileus * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Duodenal ulcer * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Gastritis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Anal Stenosis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Gastrointestinal Ulcer * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Ileus * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Oesophageal Spasm * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Peptic Ulcer * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Rectal Haemorrhage * 1  0/871 (0.00%)  0/844 (0.00%)  2/234 (0.85%) 
General disorders       
General physical health deterioration * 1  15/871 (1.72%)  10/844 (1.18%)  6/234 (2.56%) 
Disease progression * 1  10/871 (1.15%)  7/844 (0.83%)  11/234 (4.70%) 
Death * 1  5/871 (0.57%)  1/844 (0.12%)  0/234 (0.00%) 
Oedema peripheral * 1  2/871 (0.23%)  3/844 (0.36%)  0/234 (0.00%) 
Fatigue * 1  5/871 (0.57%)  0/844 (0.00%)  2/234 (0.85%) 
Gait disturbance * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Pain * 1  3/871 (0.34%)  0/844 (0.00%)  0/234 (0.00%) 
Performance status decreased * 1  0/871 (0.00%)  2/844 (0.24%)  0/234 (0.00%) 
Pyrexia * 1  2/871 (0.23%)  1/844 (0.12%)  3/234 (1.28%) 
Asthenia * 1  0/871 (0.00%)  1/844 (0.12%)  5/234 (2.14%) 
Chest pain * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Device dislocation * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Drowning * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Generalized oedema * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Medical device complication * 1  0/871 (0.00%)  1/844 (0.12%)  1/234 (0.43%) 
Non-cardiac chest pain * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Oedema * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Sudden death * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Suprapubic pain * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Adverse drug reaction * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Device occlusion * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Local swelling * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Device Malfunction * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Medical Device Pain * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Multi-Organ Failure * 1  3/871 (0.34%)  0/844 (0.00%)  0/234 (0.00%) 
Hepatobiliary disorders       
Bile duct obstruction * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Cholecystitis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Cholecystitis chronic * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Hepatic failure * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Hepatic function abnormal * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Jaundice * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Jaundice cholestatic * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Bile Duct Stone * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Cholangitis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Hepatic Cyst * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Immune system disorders       
Anaphylactic shock * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Drug hypersensitivity * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Infections and infestations       
Pneumonia * 1  14/871 (1.61%)  7/844 (0.83%)  8/234 (3.42%) 
Urinary tract infection * 1  8/871 (0.92%)  5/844 (0.59%)  10/234 (4.27%) 
Urosepsis * 1  5/871 (0.57%)  3/844 (0.36%)  4/234 (1.71%) 
Sepsis * 1  3/871 (0.34%)  4/844 (0.47%)  1/234 (0.43%) 
Gastroenteritis * 1  4/871 (0.46%)  1/844 (0.12%)  0/234 (0.00%) 
Device related infection * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Bronchitis * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Cellulitis * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Herpes zoster * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Appendicitis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Appendicitis perforated * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Bacteraemia * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Diverticulitis * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Gallbladder abscess * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Gastroenteritis staphylococcal * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Lower respiratory tract infection * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Osteomyelitis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Peritonitis * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Respiratory tract infection * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Septic shock * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Urinary tract infection fungal * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Viral infection * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Wound infection * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Chronic sinusitis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Acute Sinusitis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Arthritis Bacterial * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Cholecystitis Infective * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Clostridium Difficile Colitis * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Clostridium Difficile Sepsis * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Erysipelas * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Escherichia Urinary Tract Infection * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Infected Dermal Cyst * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Infection * 1  2/871 (0.23%)  0/844 (0.00%)  3/234 (1.28%) 
Meningitis Pneumococcal * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Postoperative Wound Infection * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Pulmonary Sepsis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Pyelonephritis Acute * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Upper Respiratory Tract Infection * 1  0/871 (0.00%)  0/844 (0.00%)  2/234 (0.85%) 
Injury, poisoning and procedural complications       
Fall * 1  12/871 (1.38%)  3/844 (0.36%)  2/234 (0.85%) 
Femoral neck fracture * 1  7/871 (0.80%)  0/844 (0.00%)  0/234 (0.00%) 
Femur fracture * 1  3/871 (0.34%)  2/844 (0.24%)  1/234 (0.43%) 
Spinal compression fracture * 1  4/871 (0.46%)  1/844 (0.12%)  0/234 (0.00%) 
Road traffic accident * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Humerus fracture * 1  4/871 (0.46%)  0/844 (0.00%)  1/234 (0.43%) 
Wrist fracture * 1  3/871 (0.34%)  0/844 (0.00%)  0/234 (0.00%) 
Hip fracture * 1  3/871 (0.34%)  2/844 (0.24%)  1/234 (0.43%) 
Subdural haematoma * 1  0/871 (0.00%)  2/844 (0.24%)  2/234 (0.85%) 
Toxicity to various agents * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Cystitis radiation * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Ankle fracture * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Chest injury * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Clavicle fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Extradural haematoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Facial bones fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Foreign body * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Gastroenteritis radiation * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Hand fracture * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Head injury * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Lumbar vertebral fracture * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Post procedural haemorrhage * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Radiation oesophagitis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Radius fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Skeletal injury * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Subdural haemorrhage * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Tibia fracture * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Traumatic fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Traumatic intracranial haemorrhage * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Upper limb fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Contrast media reaction * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Contusion * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Lower limb fracture * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Post procedural haematuria * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Procedural pain * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Pubis fracture * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Vascular pseudoaneurysm * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Back Injury * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Cervical Vertebral Fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Joint Injury * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Post Procedural Bile Leak * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Renal Haematoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Rib Fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Spinal Fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Sternal Fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Thoracic Vertebral Fracture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Investigations       
Electrocardiogram QT prolonged * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Haemoglobin decreased * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Platelet count decreased * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Hepatic enzyme increased * 1  0/871 (0.00%)  2/844 (0.24%)  0/234 (0.00%) 
Arteriogram coronary * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Blood creatinine increased * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Coagulation time prolonged * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Eastern cooperative oncology group performance status worsened * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
International normalized ratio increased * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Electrocardiogram repolarisation abnormality * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Weight decreased * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Biopsy * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Ejection Fraction Decreased * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Electrocardiogram Abnormal * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metabolism and nutrition disorders       
Dehydration * 1  2/871 (0.23%)  3/844 (0.36%)  1/234 (0.43%) 
Decreased appetite * 1  2/871 (0.23%)  2/844 (0.24%)  1/234 (0.43%) 
Hypercalcaemia * 1  3/871 (0.34%)  0/844 (0.00%)  0/234 (0.00%) 
Hypoglycaemia * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Cachexia * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Fluid retention * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Hyperkalaemia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Hypokalaemia * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Hyponatraemia * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Type 2 diabetes mellitus * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metabolic acidosis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Hypophagia * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Malnutrition * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Musculoskeletal and connective tissue disorders       
Pathological Fracture * 1  15/871 (1.72%)  6/844 (0.71%)  3/234 (1.28%) 
Back pain * 1  4/871 (0.46%)  5/844 (0.59%)  0/234 (0.00%) 
Bone pain * 1  3/871 (0.34%)  5/844 (0.59%)  0/234 (0.00%) 
Osteoarthritis * 1  8/871 (0.92%)  2/844 (0.24%)  2/234 (0.85%) 
Intervertebral disc protrusion * 1  4/871 (0.46%)  1/844 (0.12%)  0/234 (0.00%) 
Muscular weakness * 1  1/871 (0.11%)  2/844 (0.24%)  1/234 (0.43%) 
Musculoskeletal chest pain * 1  0/871 (0.00%)  3/844 (0.36%)  0/234 (0.00%) 
Arthralgia * 1  2/871 (0.23%)  0/844 (0.00%)  1/234 (0.43%) 
Neck pain * 1  0/871 (0.00%)  2/844 (0.24%)  0/234 (0.00%) 
Osteolysis * 1  0/871 (0.00%)  2/844 (0.24%)  0/234 (0.00%) 
Spinal column stenosis * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Lumbar spinal stenosis * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Musculoskeletal pain * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Myalgia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Myopathy * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Periostitis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Rhabdomyolysis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Spinal osteoarthritis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Arthritis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Groin pain * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Pain in extremity * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Bursitis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Cervical Spinal Stenosis * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Synovial Cyst * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastatic pain * 1  18/871 (2.07%)  17/844 (2.01%)  4/234 (1.71%) 
Cancer pain * 1  3/871 (0.34%)  3/844 (0.36%)  2/234 (0.85%) 
Gastric cancer * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Transitional cell carcinoma * 1  4/871 (0.46%)  0/844 (0.00%)  2/234 (0.85%) 
Adenocarcinoma of colon * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Lung adenocarcinoma * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Malignant pleural effusion * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Metastases to central nervous system * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Metastases to liver * 1  0/871 (0.00%)  2/844 (0.24%)  0/234 (0.00%) 
Metastases to meninges * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Metastases to soft tissue * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Metastases to spine * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Prostate cancer metastatic * 1  0/871 (0.00%)  2/844 (0.24%)  1/234 (0.43%) 
Rectal cancer * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Malignant melanoma * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Prostate cancer * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Tonsil cancer * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Adenocarcinoma gastric * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Anal cancer * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Bladder cancer * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Bladder transitional cell carcinoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Colon cancer * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Colorectal cancer * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Hepatocellular carcinoma * 1  3/871 (0.34%)  0/844 (0.00%)  0/234 (0.00%) 
Intestinal adenocarcinoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Lung neoplasm malignant * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metastases to bladder * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metastases to bone * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Metastases to bone marrow * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metastases to breast * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metastases to lung * 1  0/871 (0.00%)  1/844 (0.12%)  2/234 (0.85%) 
Metastases to peritoneum * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Neuroendocrine carcinoma of the skin * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Osteosarcoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Renal cell carcinoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Small cell lung cancer limited stage * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Thyroid adenoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Tumour associated fever * 1  0/871 (0.00%)  1/844 (0.12%)  1/234 (0.43%) 
Tumour embolism * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Tumour pain * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
B-cell lymphoma * 1  3/871 (0.34%)  0/844 (0.00%)  0/234 (0.00%) 
Gastrointestinal stromal tumour * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Myelodysplastic syndrome * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Acute Myeloid Leukaemia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Basal Cell Carcinoma * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Brain Neoplasm * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Colorectal Adenocarcinoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Colorectal Cancer Metastatic * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Diffuse Large B-Cell Lymphoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Gastric Cancer Recurrent * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Gastrointestinal Cancer Metastatic * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Glioblastoma Multiforme * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metastases To Chest Wall * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metastases To Penis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metastatic Neoplasm * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Myxofibrosarcoma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Non-Hodgkin's Lymphoma * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Plasma Cell Myeloma * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Small Cell Lung Cancer * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Squamous Cell Carcinoma Of Skin * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Nervous system disorders       
Spinal cord compression * 1  35/871 (4.02%)  25/844 (2.96%)  10/234 (4.27%) 
Syncope * 1  8/871 (0.92%)  0/844 (0.00%)  3/234 (1.28%) 
Cerebrovascular accident * 1  7/871 (0.80%)  1/844 (0.12%)  0/234 (0.00%) 
Cauda equina syndrome * 1  4/871 (0.46%)  0/844 (0.00%)  0/234 (0.00%) 
Nerve root compression * 1  2/871 (0.23%)  2/844 (0.24%)  0/234 (0.00%) 
Transient ischaemic attack * 1  6/871 (0.69%)  3/844 (0.36%)  0/234 (0.00%) 
Presyncope * 1  3/871 (0.34%)  0/844 (0.00%)  0/234 (0.00%) 
Paraesthesia * 1  0/871 (0.00%)  2/844 (0.24%)  0/234 (0.00%) 
Paraparesis * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Ataxia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Brain injury * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Cerebral haemorrhage * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Cerebral infarction * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Cervicobrachial syndrome * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Coma hepatic * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Dementia * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Memory impairment * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Meningorrhagia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Metabolic encephalopathy * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Reversible ischaemic neurological deficit * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Spinal cord ischaemia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Subarachnoid haemorrhage * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Vith nerve disorder * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Complex partial seizures * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Neuralgia * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Sciatica * 1  0/871 (0.00%)  2/844 (0.24%)  0/234 (0.00%) 
Cervical Cord Compression * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Convulsion * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Cranial Nerve Paralysis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Grand Mal Convulsion * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Haemorrhage Intracranial * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Headache * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Hypoxic-Ischaemic Encephalopathy * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Lethargy * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Loss Of Consciousness * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Neurological Symptom * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Sensory Loss * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Vith Nerve Paralysis * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Dizziness * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Epiduritis * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Monoplegia * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Status Epilepticus * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Psychiatric disorders       
Confusional state * 1  1/871 (0.11%)  4/844 (0.47%)  2/234 (0.85%) 
Suicide attempt * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Depression * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Major depression * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Delirium * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Renal and urinary disorders       
Urinary retention * 1  10/871 (1.15%)  13/844 (1.54%)  3/234 (1.28%) 
Haematuria * 1  11/871 (1.26%)  12/844 (1.42%)  3/234 (1.28%) 
Urinary tract obstruction * 1  8/871 (0.92%)  9/844 (1.07%)  1/234 (0.43%) 
Hydronephrosis * 1  2/871 (0.23%)  11/844 (1.30%)  1/234 (0.43%) 
Renal failure acute * 1  6/871 (0.69%)  5/844 (0.59%)  2/234 (0.85%) 
Ureteric obstruction * 1  4/871 (0.46%)  4/844 (0.47%)  1/234 (0.43%) 
Obstructive uropathy * 1  5/871 (0.57%)  6/844 (0.71%)  3/234 (1.28%) 
Bladder outlet obstruction * 1  2/871 (0.23%)  3/844 (0.36%)  0/234 (0.00%) 
Postrenal failure * 1  2/871 (0.23%)  3/844 (0.36%)  0/234 (0.00%) 
Urinary bladder haemorrhage * 1  3/871 (0.34%)  0/844 (0.00%)  0/234 (0.00%) 
Calculus bladder * 1  1/871 (0.11%)  1/844 (0.12%)  1/234 (0.43%) 
Prerenal failure * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Renal failure * 1  3/871 (0.34%)  1/844 (0.12%)  0/234 (0.00%) 
Acute prerenal failure * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Bladder obstruction * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Renal failure chronic * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Urethral meatus stenosis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Urethral obstruction * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Urine flow decreased * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Bladder neck obstruction * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Micturition urgency * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Calculus Ureteric * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Nephrolithiasis * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Renal Colic * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Urethral Stenosis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Urinary Incontinence * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Nephrotic Syndrome * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Calculus Urinary * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Pelvic pain * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Prostatic obstruction * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Prostatitis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Testicular pain * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Epididymitis * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism * 1  6/871 (0.69%)  7/844 (0.83%)  0/234 (0.00%) 
Chronic obstructive pulmonary disease * 1  5/871 (0.57%)  3/844 (0.36%)  0/234 (0.00%) 
Dyspnoea * 1  3/871 (0.34%)  2/844 (0.24%)  0/234 (0.00%) 
Pleural effusion * 1  2/871 (0.23%)  1/844 (0.12%)  0/234 (0.00%) 
Epistaxis * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Acute pulmonary oedema * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Aspiration * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Asthma * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Haemothorax * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Hydrothorax * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Hypoxia * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Nasal polyps * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Organising pneumonia * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Pneumonia aspiration * 1  3/871 (0.34%)  0/844 (0.00%)  1/234 (0.43%) 
Pneumonitis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Pulmonary haemorrhage * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Restrictive pulmonary disease * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Tracheal obstruction extrinsic * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Bronchiectasis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Pneumothorax * 1  2/871 (0.23%)  1/844 (0.12%)  1/234 (0.43%) 
Skin and subcutaneous tissue disorders       
Toxic skin eruption * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Rash * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Swelling face * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Rash Maculo-Papular * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Surgical and medical procedures       
Cancer hormonal therapy * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Pain management * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Knee Arthroplasty * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Radical Cystectomy * 1  0/871 (0.00%)  0/844 (0.00%)  1/234 (0.43%) 
Umbilical Hernia Repair * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Vascular disorders       
Deep vein thrombosis * 1  4/871 (0.46%)  2/844 (0.24%)  0/234 (0.00%) 
Hypertension * 1  4/871 (0.46%)  0/844 (0.00%)  1/234 (0.43%) 
Hypotension * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Orthostatic hypotension * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Aortic aneurysm * 1  1/871 (0.11%)  1/844 (0.12%)  0/234 (0.00%) 
Aortic aneurysm rupture * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Circulatory collapse * 1  2/871 (0.23%)  0/844 (0.00%)  0/234 (0.00%) 
Hypovolaemic shock * 1  1/871 (0.11%)  0/844 (0.00%)  1/234 (0.43%) 
Lymphoedema * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Vena cava thrombosis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Aortic stenosis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Phlebitis * 1  0/871 (0.00%)  1/844 (0.12%)  0/234 (0.00%) 
Subclavian artery stenosis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Aneurysm * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
Peripheral Artery Stenosis * 1  1/871 (0.11%)  0/844 (0.00%)  0/234 (0.00%) 
1
Term from vocabulary, MedDRA 16.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Enzalutamide Placebo Placebo Participants Crossover to Enzalutamide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   814/871 (93.46%)   723/844 (85.66%)   180/234 (76.92%) 
Blood and lymphatic system disorders       
Anaemia * 1  76/871 (8.73%)  68/844 (8.06%)  23/234 (9.83%) 
Gastrointestinal disorders       
Nausea * 1  211/871 (24.23%)  192/844 (22.75%)  34/234 (14.53%) 
Constipation * 1  220/871 (25.26%)  145/844 (17.18%)  38/234 (16.24%) 
Diarrhoea * 1  160/871 (18.37%)  121/844 (14.34%)  20/234 (8.55%) 
Vomiting * 1  64/871 (7.35%)  70/844 (8.29%)  9/234 (3.85%) 
Abdominal pain * 1  56/871 (6.43%)  31/844 (3.67%)  4/234 (1.71%) 
General disorders       
Fatigue * 1  332/871 (38.12%)  220/844 (26.07%)  63/234 (26.92%) 
Asthenia * 1  122/871 (14.01%)  69/844 (8.18%)  15/234 (6.41%) 
Oedema peripheral * 1  115/871 (13.20%)  70/844 (8.29%)  20/234 (8.55%) 
Infections and infestations       
Urinary tract infection * 1  70/871 (8.04%)  56/844 (6.64%)  11/234 (4.70%) 
Nasopharyngitis * 1  74/871 (8.50%)  44/844 (5.21%)  6/234 (2.56%) 
Upper respiratory tract infection * 1  61/871 (7.00%)  30/844 (3.55%)  7/234 (2.99%) 
Injury, poisoning and procedural complications       
Fall * 1  136/871 (15.61%)  42/844 (4.98%)  15/234 (6.41%) 
Investigations       
Weight decreased * 1  122/871 (14.01%)  72/844 (8.53%)  26/234 (11.11%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  182/871 (20.90%)  139/844 (16.47%)  36/234 (15.38%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  280/871 (32.15%)  188/844 (22.27%)  32/234 (13.68%) 
Arthralgia * 1  206/871 (23.65%)  137/844 (16.23%)  22/234 (9.40%) 
Pain in extremity * 1  124/871 (14.24%)  97/844 (11.49%)  13/234 (5.56%) 
Bone pain * 1  100/871 (11.48%)  116/844 (13.74%)  18/234 (7.69%) 
Musculoskeletal pain * 1  112/871 (12.86%)  74/844 (8.77%)  28/234 (11.97%) 
Musculoskeletal chest pain * 1  73/871 (8.38%)  40/844 (4.74%)  5/234 (2.14%) 
Myalgia * 1  59/871 (6.77%)  49/844 (5.81%)  8/234 (3.42%) 
Muscular Weakness * 1  45/871 (5.17%)  27/844 (3.20%)  8/234 (3.42%) 
Nervous system disorders       
Headache * 1  102/871 (11.71%)  59/844 (6.99%)  15/234 (6.41%) 
Dizziness * 1  85/871 (9.76%)  54/844 (6.40%)  13/234 (5.56%) 
Dysgeusia * 1  67/871 (7.69%)  31/844 (3.67%)  5/234 (2.14%) 
Psychiatric disorders       
Insomnia * 1  78/871 (8.96%)  48/844 (5.69%)  10/234 (4.27%) 
Renal and urinary disorders       
Haematuria * 1  93/871 (10.68%)  43/844 (5.09%)  11/234 (4.70%) 
Pollakiuria * 1  62/871 (7.12%)  37/844 (4.38%)  6/234 (2.56%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  95/871 (10.91%)  58/844 (6.87%)  2/234 (0.85%) 
Dyspnoea * 1  88/871 (10.10%)  60/844 (7.11%)  14/234 (5.98%) 
Skin and subcutaneous tissue disorders       
Rash * 1  31/871 (3.56%)  21/844 (2.49%)  14/234 (5.98%) 
Vascular disorders       
Hot flush * 1  159/871 (18.25%)  66/844 (7.82%)  11/234 (4.70%) 
Hypertension * 1  148/871 (16.99%)  36/844 (4.27%)  28/234 (11.97%) 
1
Term from vocabulary, MedDRA 16.1
*
Indicates events were collected by non-systematic assessment
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.
PI agrees not to independently publish the results before the publication of the multi-center PI paper. Sponsor shall review and comment 30 days prior to submission or disclosure. If publication or disclosure contains Sponsor Confidential Information, other than study data, PI agrees to remove Confidential Information from publication or disclosure. Sponsor may request that PI delay such publication for an additional 60 days to protect the patentability of any invention described.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 8007181021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01212991    
Other Study ID Numbers: MDV3100-03
2010-020821-41 ( EudraCT Number )
C3431003 ( Other Identifier: Alias Study Number )
First Submitted: September 29, 2010
First Posted: October 1, 2010
Results First Submitted: October 8, 2014
Results First Posted: October 16, 2014
Last Update Posted: March 17, 2020