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Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Men With Hormone-refractory Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00321620
First received: May 2, 2006
Last updated: February 19, 2016
Last verified: February 2016
Results First Received: December 10, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Supportive Care
Condition: Bone Metastases
Interventions: Drug: zoledronic acid
Biological: denosumab

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled from 12 May 2006 through 18 December 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1904 participants were enrolled, however 3 were excluded from all analyses as Institutional Review Board review activities and oversight were not ensured.

Reporting Groups
  Description
Zoledronic Acid Zoledronic acid 4 mg by intravenous injection with a subcutaneous denosumab placebo once every 4 weeks
Denosumab Denosumab 120 mg subcutaneously with an intravenous zoledronic acid placebo once every 4 weeks

Participant Flow:   Overall Study
    Zoledronic Acid   Denosumab
STARTED   951   950 
Received Investigational Product   946   942 
COMPLETED   208   228 
NOT COMPLETED   743   722 
Death                269                294 
Withdrawal by Subject                164                147 
Disease progression                113                117 
Adverse Event                43                56 
Lost to Follow-up                13                9 
Physician Decision                4                1 
Noncompliance                14                7 
Protocol deviation                4                3 
Ineligibility determined                2                3 
Participant request                75                52 
Other                42                33 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Zoledronic Acid Zoledronic acid 4 mg by intravenous injection with a subcutaneous denosumab placebo once every 4 weeks
Denosumab Denosumab 120 mg subcutaneously with an intravenous zoledronic acid placebo once every 4 weeks
Total Total of all reporting groups

Baseline Measures
   Zoledronic Acid   Denosumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 951   950   1901 
Age 
[Units: Years]
Mean (Standard Deviation)
 71.0  (8.4)   70.5  (8.7)   70.8  (8.6) 
Gender 
[Units: Participants]
     
Female   0   0   0 
Male   951   950   1901 
Race/Ethnicity, Customized 
[Units: Participants]
     
White or Caucasian   810   829   1639 
Black or African American   35   38   73 
Hispanic or Latino   57   45   102 
Asian   26   22   48 
Native Hawaiian or Other Pacific Islander   1   1   2 
Other   22   15   37 
Prostate-Specific Antigen (PSA) Stratification Factor 
[Units: Participants]
     
PSA level < 10 ng/mL   145   145   290 
PSA level ≥ 10 ng/mL   806   805   1611 
Previous Skeletal-Related Event (SRE) Stratification Factor 
[Units: Participants]
     
Yes   231   232   463 
No   720   718   1438 
Current Prostate Cancer Chemotherapy Stratification Factor [1] 
[Units: Participants]
     
Yes   132   132   264 
No   819   818   1637 
[1] Defined as within 6 weeks before randomization


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to the First On-Study SRE (Non-inferiority)   [ Time Frame: Up to 40.5 months ]

2.  Secondary:   Time to the First On-Study SRE (Superiority)   [ Time Frame: Up to 40.5 months ]

3.  Secondary:   Time to the First-And-Subsequent On-Study SRE   [ Time Frame: Up to 40.5 months ]


  Serious Adverse Events
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Time Frame up to 3 years 5 months
Additional Description

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

One subject who was randomized to zoledronic acid and received denosumab as the 1st investigational product was analyzed on the denosumab arm for safety analyses.


Reporting Groups
  Description
Zoledronic Acid 4 mg Q4W No text entered.
Denosumab 120 mg Q4W No text entered.

Serious Adverse Events
    Zoledronic Acid 4 mg Q4W   Denosumab 120 mg Q4W
Total, serious adverse events     
# participants affected / at risk   568/945 (60.11%)   594/943 (62.99%) 
Blood and lymphatic system disorders     
Anaemia † 1     
# participants affected / at risk   82/945 (8.68%)   108/943 (11.45%) 
Anaemia of malignant disease † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Coagulopathy † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Disseminated intravascular coagulation † 1     
# participants affected / at risk   2/945 (0.21%)   3/943 (0.32%) 
Febrile bone marrow aplasia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Febrile neutropenia † 1     
# participants affected / at risk   8/945 (0.85%)   8/943 (0.85%) 
Haemorrhagic anaemia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Heparin-induced thrombocytopenia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hypercoagulation † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Leukopenia † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Lymphadenopathy † 1     
# participants affected / at risk   0/945 (0.00%)   3/943 (0.32%) 
Neutropenia † 1     
# participants affected / at risk   4/945 (0.42%)   10/943 (1.06%) 
Normochromic normocytic anaemia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Pancytopenia † 1     
# participants affected / at risk   3/945 (0.32%)   1/943 (0.11%) 
Splenic infarction † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Thrombocytopenia † 1     
# participants affected / at risk   5/945 (0.53%)   10/943 (1.06%) 
Cardiac disorders     
Acute coronary syndrome † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Acute myocardial infarction † 1     
# participants affected / at risk   7/945 (0.74%)   5/943 (0.53%) 
Angina pectoris † 1     
# participants affected / at risk   5/945 (0.53%)   1/943 (0.11%) 
Angina unstable † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Arrhythmia † 1     
# participants affected / at risk   2/945 (0.21%)   6/943 (0.64%) 
Arteriosclerosis coronary artery † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Atrial fibrillation † 1     
# participants affected / at risk   8/945 (0.85%)   10/943 (1.06%) 
Atrial flutter † 1     
# participants affected / at risk   3/945 (0.32%)   0/943 (0.00%) 
Atrial tachycardia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Atrioventricular block complete † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Bundle branch block right † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Cardiac arrest † 1     
# participants affected / at risk   4/945 (0.42%)   5/943 (0.53%) 
Cardiac asthma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Cardiac failure † 1     
# participants affected / at risk   23/945 (2.43%)   21/943 (2.23%) 
Cardiac failure acute † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Cardiac failure congestive † 1     
# participants affected / at risk   7/945 (0.74%)   8/943 (0.85%) 
Cardio-respiratory arrest † 1     
# participants affected / at risk   12/945 (1.27%)   7/943 (0.74%) 
Cardiogenic shock † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Cardiomegaly † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Cardiopulmonary failure † 1     
# participants affected / at risk   6/945 (0.63%)   2/943 (0.21%) 
Cardiovascular insufficiency † 1     
# participants affected / at risk   3/945 (0.32%)   1/943 (0.11%) 
Coronary artery disease † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Coronary artery stenosis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Ischaemic cardiomyopathy † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Left ventricular failure † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Myocardial infarction † 1     
# participants affected / at risk   13/945 (1.38%)   9/943 (0.95%) 
Myocardial ischaemia † 1     
# participants affected / at risk   6/945 (0.63%)   5/943 (0.53%) 
Sick sinus syndrome † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Supraventricular tachycardia † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Tachyarrhythmia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Tachycardia † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Ventricular fibrillation † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Ear and labyrinth disorders     
Acute vestibular syndrome † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hypoacusis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Vertigo † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Endocrine disorders     
Adrenal insufficiency † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Eye disorders     
Blindness unilateral † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Cataract † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Diplopia † 1     
# participants affected / at risk   0/945 (0.00%)   3/943 (0.32%) 
Retinal artery thrombosis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Vision blurred † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Visual impairment † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Gastrointestinal disorders     
Abdominal pain † 1     
# participants affected / at risk   12/945 (1.27%)   8/943 (0.85%) 
Abdominal pain lower † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Abdominal pain upper † 1     
# participants affected / at risk   3/945 (0.32%)   3/943 (0.32%) 
Anal fissure † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Anal haemorrhage † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Ascites † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Colitis † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Colitis ulcerative † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Colonic obstruction † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Constipation † 1     
# participants affected / at risk   9/945 (0.95%)   5/943 (0.53%) 
Diarrhoea † 1     
# participants affected / at risk   13/945 (1.38%)   12/943 (1.27%) 
Dysphagia † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Enterovesical fistula † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Faecal incontinence † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Faecaloma † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Faeces discoloured † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Gastric ulcer † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Gastric ulcer haemorrhage † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Gastric ulcer perforation † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Gastritis erosive † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Gastrointestinal disorder † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Gastrointestinal haemorrhage † 1     
# participants affected / at risk   4/945 (0.42%)   3/943 (0.32%) 
Gastrointestinal obstruction † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Gingival bleeding † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Haematemesis † 1     
# participants affected / at risk   3/945 (0.32%)   2/943 (0.21%) 
Haematochezia † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Ileus † 1     
# participants affected / at risk   0/945 (0.00%)   3/943 (0.32%) 
Ileus paralytic † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Inguinal hernia † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Intestinal obstruction † 1     
# participants affected / at risk   4/945 (0.42%)   4/943 (0.42%) 
Intestinal perforation † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Lower gastrointestinal haemorrhage † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Melaena † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Nausea † 1     
# participants affected / at risk   14/945 (1.48%)   8/943 (0.85%) 
Obstruction gastric † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Odynophagia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Oesophageal ulcer † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Oesophagitis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Pancreatitis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Pancreatitis acute † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Peritonitis † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Proctalgia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Rectal haemorrhage † 1     
# participants affected / at risk   3/945 (0.32%)   3/943 (0.32%) 
Rectal stenosis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Rectourethral fistula † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Reflux gastritis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Retroperitoneal haematoma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Retroperitoneal haemorrhage † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Small intestinal obstruction † 1     
# participants affected / at risk   0/945 (0.00%)   3/943 (0.32%) 
Stomatitis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Subileus † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Upper gastrointestinal haemorrhage † 1     
# participants affected / at risk   3/945 (0.32%)   6/943 (0.64%) 
Vomiting † 1     
# participants affected / at risk   22/945 (2.33%)   24/943 (2.55%) 
General disorders     
Abasia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Asthenia † 1     
# participants affected / at risk   29/945 (3.07%)   37/943 (3.92%) 
Catheter related complication † 1     
# participants affected / at risk   3/945 (0.32%)   2/943 (0.21%) 
Catheter site pain † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Chest discomfort † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Chest pain † 1     
# participants affected / at risk   13/945 (1.38%)   9/943 (0.95%) 
Chills † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Death † 1     
# participants affected / at risk   10/945 (1.06%)   11/943 (1.17%) 
Discomfort † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Disease progression † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Drug intolerance † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Fatigue † 1     
# participants affected / at risk   10/945 (1.06%)   20/943 (2.12%) 
Gait disturbance † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
General physical health deterioration † 1     
# participants affected / at risk   28/945 (2.96%)   29/943 (3.08%) 
Generalised oedema † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Hernia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Impaired healing † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Inflammation † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Localised oedema † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Malaise † 1     
# participants affected / at risk   3/945 (0.32%)   3/943 (0.32%) 
Mucosal inflammation † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Multi-organ failure † 1     
# participants affected / at risk   18/945 (1.90%)   18/943 (1.91%) 
Oedema † 1     
# participants affected / at risk   3/945 (0.32%)   1/943 (0.11%) 
Oedema peripheral † 1     
# participants affected / at risk   8/945 (0.85%)   13/943 (1.38%) 
Pain † 1     
# participants affected / at risk   12/945 (1.27%)   16/943 (1.70%) 
Performance status decreased † 1     
# participants affected / at risk   2/945 (0.21%)   9/943 (0.95%) 
Pyrexia † 1     
# participants affected / at risk   18/945 (1.90%)   19/943 (2.01%) 
Sudden death † 1     
# participants affected / at risk   2/945 (0.21%)   3/943 (0.32%) 
Suprapubic pain † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Terminal state † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hepatobiliary disorders     
Bile duct obstruction † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Bile duct stone † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Biliary tract disorder † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Cholecystitis † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Cholecystitis acute † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Cholelithiasis † 1     
# participants affected / at risk   3/945 (0.32%)   0/943 (0.00%) 
Cholelithiasis obstructive † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hepatic failure † 1     
# participants affected / at risk   6/945 (0.63%)   10/943 (1.06%) 
Hepatitis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hepatomegaly † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hepatorenal syndrome † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hyperbilirubinaemia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Jaundice † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Jaundice cholestatic † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Infections and infestations     
Abscess intestinal † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Alveolar osteitis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Anal abscess † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Appendicitis † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Bacteraemia † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Bronchitis † 1     
# participants affected / at risk   1/945 (0.11%)   6/943 (0.64%) 
Bronchopneumonia † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Candidiasis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Catheter related infection † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Cellulitis † 1     
# participants affected / at risk   4/945 (0.42%)   6/943 (0.64%) 
Central line infection † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Cholecystitis infective † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Clostridial infection † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Clostridium difficile colitis † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Cystitis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Dermo-hypodermitis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Device related infection † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Diverticulitis † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Endotoxaemia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Enterococcal sepsis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Erysipelas † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Fungal oesophagitis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Gangrene † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Gastroenteritis † 1     
# participants affected / at risk   3/945 (0.32%)   1/943 (0.11%) 
Gastroenteritis viral † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Gastrointestinal infection † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Herpes zoster † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Infection † 1     
# participants affected / at risk   3/945 (0.32%)   1/943 (0.11%) 
Infective exacerbation of chronic obstructive airways disease † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Influenza † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Kidney infection † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Lobar pneumonia † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Lower respiratory tract infection † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Ludwig angina † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Lung infection † 1     
# participants affected / at risk   3/945 (0.32%)   2/943 (0.21%) 
Meningitis bacterial † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Necrotising fasciitis † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Neutropenic sepsis † 1     
# participants affected / at risk   0/945 (0.00%)   3/943 (0.32%) 
Oesophageal candidiasis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Oral candidiasis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Orchitis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Osteomyelitis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Otitis media † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Penile abscess † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Peridiverticulitis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Perirectal abscess † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Pneumonia † 1     
# participants affected / at risk   24/945 (2.54%)   40/943 (4.24%) 
Pneumonia bacterial † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Pneumonia klebsiella † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Post procedural sepsis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Postoperative wound infection † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Pulmonary sepsis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Pyelonephritis † 1     
# participants affected / at risk   2/945 (0.21%)   4/943 (0.42%) 
Pyelonephritis acute † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Pyelonephritis chronic † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Renal abscess † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Scrotal abscess † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Sepsis † 1     
# participants affected / at risk   11/945 (1.16%)   12/943 (1.27%) 
Septic shock † 1     
# participants affected / at risk   4/945 (0.42%)   5/943 (0.53%) 
Skin infection † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Staphylococcal infection † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Staphylococcal sepsis † 1     
# participants affected / at risk   0/945 (0.00%)   3/943 (0.32%) 
Subcutaneous abscess † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Tongue abscess † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Urinary tract infection † 1     
# participants affected / at risk   30/945 (3.17%)   28/943 (2.97%) 
Urosepsis † 1     
# participants affected / at risk   4/945 (0.42%)   5/943 (0.53%) 
Wound infection † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Injury, poisoning and procedural complications     
Cardiac pacemaker malfunction † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Concussion † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Contusion † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Cystitis radiation † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Device failure † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Device malfunction † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Drug toxicity † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Extradural haematoma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Fall † 1     
# participants affected / at risk   3/945 (0.32%)   4/943 (0.42%) 
Femur fracture † 1     
# participants affected / at risk   3/945 (0.32%)   4/943 (0.42%) 
Fracture † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Gastroenteritis radiation † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Head injury † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Ilium fracture † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Joint dislocation † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Kidney rupture † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Lumbar vertebral fracture † 1     
# participants affected / at risk   4/945 (0.42%)   0/943 (0.00%) 
Medical device discomfort † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Mouth injury † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Overdose † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Poisoning † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Post procedural haemorrhage † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Procedural pain † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Renal haematoma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Rib fracture † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Skin laceration † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Stent occlusion † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Sternal fracture † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Subdural haematoma † 1     
# participants affected / at risk   2/945 (0.21%)   7/943 (0.74%) 
Subdural haemorrhage † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Tendon rupture † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Thoracic vertebral fracture † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Tibia fracture † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Traumatic lung injury † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Wound dehiscence † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Investigations     
Aspiration bronchial † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Blood alkaline phosphatase increased † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Blood bilirubin increased † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Blood creatinine † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Blood creatinine increased † 1     
# participants affected / at risk   0/945 (0.00%)   5/943 (0.53%) 
Blood pressure systolic abnormal † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Blood urine present † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
General physical condition abnormal † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Glomerular filtration rate † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Haemoglobin decreased † 1     
# participants affected / at risk   6/945 (0.63%)   2/943 (0.21%) 
Hepatic enzyme increased † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
International normalised ratio decreased † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Liver function test abnormal † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Occult blood positive † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Platelet count decreased † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Prostatic specific antigen increased † 1     
# participants affected / at risk   1/945 (0.11%)   4/943 (0.42%) 
Prothrombin time prolonged † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Urine output decreased † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Weight decreased † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Metabolism and nutrition disorders     
Cachexia † 1     
# participants affected / at risk   12/945 (1.27%)   14/943 (1.48%) 
Decreased appetite † 1     
# participants affected / at risk   13/945 (1.38%)   13/943 (1.38%) 
Dehydration † 1     
# participants affected / at risk   19/945 (2.01%)   36/943 (3.82%) 
Diabetes mellitus † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Electrolyte imbalance † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Failure to thrive † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Feeding disorder † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Fluid overload † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Gout † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hypercreatininaemia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hyperglycaemia † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Hyperkalaemia † 1     
# participants affected / at risk   5/945 (0.53%)   6/943 (0.64%) 
Hypermetabolism † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hypernatraemia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hyperosmolar state † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hypoalbuminaemia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hypocalcaemia † 1     
# participants affected / at risk   7/945 (0.74%)   24/943 (2.55%) 
Hypoglycaemia † 1     
# participants affected / at risk   3/945 (0.32%)   4/943 (0.42%) 
Hypokalaemia † 1     
# participants affected / at risk   5/945 (0.53%)   4/943 (0.42%) 
Hypomagnesaemia † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Hyponatraemia † 1     
# participants affected / at risk   4/945 (0.42%)   4/943 (0.42%) 
Hypophosphataemia † 1     
# participants affected / at risk   0/945 (0.00%)   6/943 (0.64%) 
Metabolic acidosis † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Metabolic disorder † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Polydipsia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   9/945 (0.95%)   11/943 (1.17%) 
Back pain † 1     
# participants affected / at risk   36/945 (3.81%)   29/943 (3.08%) 
Bone pain † 1     
# participants affected / at risk   34/945 (3.60%)   24/943 (2.55%) 
Cervical spinal stenosis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Flank pain † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Groin pain † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Intervertebral disc disorder † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Intervertebral disc protrusion † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Joint effusion † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Joint range of motion decreased † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Joint swelling † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Lumbar spinal stenosis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Mobility decreased † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Muscle haemorrhage † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Muscular weakness † 1     
# participants affected / at risk   4/945 (0.42%)   9/943 (0.95%) 
Musculoskeletal chest pain † 1     
# participants affected / at risk   2/945 (0.21%)   3/943 (0.32%) 
Musculoskeletal pain † 1     
# participants affected / at risk   7/945 (0.74%)   1/943 (0.11%) 
Myalgia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Myopathy † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Neck mass † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Neck pain † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Osteitis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Osteoarthritis † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Osteochondrosis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Osteonecrosis † 1     
# participants affected / at risk   4/945 (0.42%)   14/943 (1.48%) 
Osteoporosis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Pain in extremity † 1     
# participants affected / at risk   20/945 (2.12%)   10/943 (1.06%) 
Pathological fracture † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Rhabdomyolysis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Sarcopenia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Spinal column stenosis † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Spinal disorder † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Spondylolisthesis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bile duct cancer † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Bladder cancer † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Bladder transitional cell carcinoma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Cancer pain † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Colon cancer † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Gastric cancer † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Lung adenocarcinoma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Lung carcinoma cell type unspecified recurrent † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Malignant neoplasm progression † 1     
# participants affected / at risk   3/945 (0.32%)   2/943 (0.21%) 
Meningioma benign † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Metastases to bladder † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Metastases to bone † 1     
# participants affected / at risk   9/945 (0.95%)   10/943 (1.06%) 
Metastases to bone marrow † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Metastases to central nervous system † 1     
# participants affected / at risk   6/945 (0.63%)   14/943 (1.48%) 
Metastases to liver † 1     
# participants affected / at risk   5/945 (0.53%)   13/943 (1.38%) 
Metastases to lung † 1     
# participants affected / at risk   4/945 (0.42%)   4/943 (0.42%) 
Metastases to lymph nodes † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Metastases to meninges † 1     
# participants affected / at risk   5/945 (0.53%)   3/943 (0.32%) 
Metastases to rectum † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Metastasis † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Metastatic neoplasm † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Metastatic pain † 1     
# participants affected / at risk   3/945 (0.32%)   5/943 (0.53%) 
Nasal sinus cancer † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Neoplasm progression † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Neoplasm prostate † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Pancreatic carcinoma † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Pancreatic carcinoma metastatic † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Paraneoplastic syndrome † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Pituitary tumour benign † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Prostate cancer † 1     
# participants affected / at risk   56/945 (5.93%)   34/943 (3.61%) 
Prostate cancer metastatic † 1     
# participants affected / at risk   17/945 (1.80%)   8/943 (0.85%) 
Rectal cancer † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Renal cell carcinoma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Transitional cell carcinoma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Waldenstrom's macroglobulinaemia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Nervous system disorders     
Balance disorder † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Brown-Sequard syndrome † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Cauda equina syndrome † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Cerebral artery embolism † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Cerebral haematoma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Cerebral haemorrhage † 1     
# participants affected / at risk   5/945 (0.53%)   4/943 (0.42%) 
Cerebral infarction † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Cerebral ischaemia † 1     
# participants affected / at risk   4/945 (0.42%)   5/943 (0.53%) 
Cerebrovascular accident † 1     
# participants affected / at risk   5/945 (0.53%)   15/943 (1.59%) 
Cerebrovascular disorder † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Cervical cord compression † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Cognitive disorder † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Convulsion † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Depressed level of consciousness † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Diabetic hyperglycaemic coma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Diplegia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Dizziness † 1     
# participants affected / at risk   3/945 (0.32%)   3/943 (0.32%) 
Dysaesthesia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Dysarthria † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Embolic stroke † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Encephalitis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Epidural lipomatosis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Facial palsy † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Facial paresis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Grand mal convulsion † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Haemorrhage intracranial † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Haemorrhagic stroke † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Headache † 1     
# participants affected / at risk   4/945 (0.42%)   1/943 (0.11%) 
Hemiparesis † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Hemiplegia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hepatic encephalopathy † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Hypertonia † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hypoaesthesia † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Hypotonia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Intracranial pressure increased † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Ischaemic stroke † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Lethargy † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Loss of consciousness † 1     
# participants affected / at risk   2/945 (0.21%)   3/943 (0.32%) 
Mental impairment † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Monoparesis † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Myoclonus † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Nerve root compression † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Neuralgia † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Neurological decompensation † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Paraesthesia † 1     
# participants affected / at risk   4/945 (0.42%)   1/943 (0.11%) 
Paralysis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Paraparesis † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Paraplegia † 1     
# participants affected / at risk   5/945 (0.53%)   4/943 (0.42%) 
Peripheral motor neuropathy † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Peripheral sensorimotor neuropathy † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Polyneuropathy † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Presyncope † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Radicular syndrome † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Sciatica † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Somnolence † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Spinal cord compression † 1     
# participants affected / at risk   33/945 (3.49%)   24/943 (2.55%) 
Spinal cord ischaemia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Subarachnoid haemorrhage † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Syncope † 1     
# participants affected / at risk   6/945 (0.63%)   10/943 (1.06%) 
Transient ischaemic attack † 1     
# participants affected / at risk   4/945 (0.42%)   3/943 (0.32%) 
Trigeminal neuralgia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Psychiatric disorders     
Abnormal behaviour † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Agitation † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Anxiety † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Confusional state † 1     
# participants affected / at risk   10/945 (1.06%)   12/943 (1.27%) 
Delirium † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Depression † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Disorientation † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Emotional distress † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hypochondriasis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Mental status changes † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Sopor † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Renal and urinary disorders     
Anuria † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Azotaemia † 1     
# participants affected / at risk   4/945 (0.42%)   1/943 (0.11%) 
Bladder obstruction † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Bladder perforation † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Calculus bladder † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Calculus ureteric † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Calculus urinary † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Dysuria † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Faecaluria † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Haematuria † 1     
# participants affected / at risk   37/945 (3.92%)   23/943 (2.44%) 
Haemorrhage urinary tract † 1     
# participants affected / at risk   1/945 (0.11%)   3/943 (0.32%) 
Hydronephrosis † 1     
# participants affected / at risk   12/945 (1.27%)   19/943 (2.01%) 
Neurogenic bladder † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Obstructive uropathy † 1     
# participants affected / at risk   4/945 (0.42%)   2/943 (0.21%) 
Oliguria † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Pollakiuria † 1     
# participants affected / at risk   0/945 (0.00%)   2/943 (0.21%) 
Polyuria † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Renal colic † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Renal cyst † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Renal disorder † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Renal failure † 1     
# participants affected / at risk   28/945 (2.96%)   26/943 (2.76%) 
Renal failure acute † 1     
# participants affected / at risk   16/945 (1.69%)   18/943 (1.91%) 
Renal failure chronic † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Renal impairment † 1     
# participants affected / at risk   5/945 (0.53%)   2/943 (0.21%) 
Renal pain † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Ureteric obstruction † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Urethral haemorrhage † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Urethral obstruction † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Urethral stenosis † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Urinary bladder haemorrhage † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Urinary incontinence † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Urinary retention † 1     
# participants affected / at risk   35/945 (3.70%)   32/943 (3.39%) 
Urinary tract disorder † 1     
# participants affected / at risk   0/945 (0.00%)   3/943 (0.32%) 
Urinary tract obstruction † 1     
# participants affected / at risk   6/945 (0.63%)   5/943 (0.53%) 
Urine odour abnormal † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Genital pain † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Oedema genital † 1     
# participants affected / at risk   4/945 (0.42%)   0/943 (0.00%) 
Pelvic pain † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Penile pain † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Perineal pain † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Prostatic cyst † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Prostatic disorder † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Prostatic haemorrhage † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Prostatic obstruction † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Prostatitis † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Prostatomegaly † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Scrotal oedema † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Scrotal pain † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema † 1     
# participants affected / at risk   3/945 (0.32%)   2/943 (0.21%) 
Acute respiratory distress syndrome † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Acute respiratory failure † 1     
# participants affected / at risk   4/945 (0.42%)   1/943 (0.11%) 
Asthma † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Bronchopneumopathy † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Chronic obstructive pulmonary disease † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Chronic respiratory failure † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Cough † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Dyspnoea † 1     
# participants affected / at risk   28/945 (2.96%)   36/943 (3.82%) 
Dyspnoea exertional † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Emphysema † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Epistaxis † 1     
# participants affected / at risk   2/945 (0.21%)   4/943 (0.42%) 
Haemoptysis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Haemothorax † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Hydrothorax † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Hypoxia † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Interstitial lung disease † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Lung disorder † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Lung infiltration † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Orthopnoea † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Pleural effusion † 1     
# participants affected / at risk   9/945 (0.95%)   12/943 (1.27%) 
Pleural haemorrhage † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Pleurisy † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Pneumonitis † 1     
# participants affected / at risk   1/945 (0.11%)   2/943 (0.21%) 
Pneumothorax † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Pulmonary embolism † 1     
# participants affected / at risk   16/945 (1.69%)   20/943 (2.12%) 
Pulmonary hypertension † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Pulmonary oedema † 1     
# participants affected / at risk   5/945 (0.53%)   3/943 (0.32%) 
Pulmonary thrombosis † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Respiratory acidosis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Respiratory disorder † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Respiratory distress † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Respiratory failure † 1     
# participants affected / at risk   14/945 (1.48%)   24/943 (2.55%) 
Respiratory tract congestion † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Tachypnoea † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Decubitus ulcer † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Erythema † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hypoaesthesia facial † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Periorbital oedema † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Purpura † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Skin toxicity † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Skin ulcer † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Stasis dermatitis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Social circumstances     
Walking disability † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Surgical and medical procedures     
Catheter placement † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Ostectomy † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Spinal operation † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Transurethral prostatectomy † 1     
# participants affected / at risk   3/945 (0.32%)   2/943 (0.21%) 
Ureteral stent insertion † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Vascular disorders     
Accelerated hypertension † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Aortic dissection † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Circulatory collapse † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Deep vein thrombosis † 1     
# participants affected / at risk   8/945 (0.85%)   8/943 (0.85%) 
Embolism † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Extremity necrosis † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Extrinsic vascular compression † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Haematoma † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Haemorrhage † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Hypertension † 1     
# participants affected / at risk   3/945 (0.32%)   5/943 (0.53%) 
Hypertensive crisis † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Hypotension † 1     
# participants affected / at risk   8/945 (0.85%)   8/943 (0.85%) 
Hypovolaemic shock † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Orthostatic hypotension † 1     
# participants affected / at risk   0/945 (0.00%)   1/943 (0.11%) 
Pelvic venous thrombosis † 1     
# participants affected / at risk   2/945 (0.21%)   0/943 (0.00%) 
Phlebitis † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Shock † 1     
# participants affected / at risk   1/945 (0.11%)   1/943 (0.11%) 
Thrombophlebitis † 1     
# participants affected / at risk   1/945 (0.11%)   0/943 (0.00%) 
Thrombosis † 1     
# participants affected / at risk   3/945 (0.32%)   0/943 (0.00%) 
Venous thrombosis † 1     
# participants affected / at risk   2/945 (0.21%)   2/943 (0.21%) 
Venous thrombosis limb † 1     
# participants affected / at risk   2/945 (0.21%)   1/943 (0.11%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 12.1




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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00321620     History of Changes
Other Study ID Numbers: 20050103
Study First Received: May 2, 2006
Results First Received: December 10, 2010
Last Updated: February 19, 2016
Health Authority: Argentina: Ministry of Health
Australia: Therapeutic Goods Administration
Austria: Secretariat of Health
Belgium: Pharmaceutical Inspectorate
Brazil: Ministry of Health
Bulgaria: Ministry of Health
Canada: Health Products and Food Branch
Chile: Health Ministry
Czech Republic: State Institute for Drug Control
Denmark: Ministry of Health
Estonia: State Agency of Medicines
France: Ministry of Health
Germancy: Federal Institute for Drugs and Medical Devices
Greece: National Organization for Medicines
Guatemala: Ministry of Health
Hungary: Ministry of Health, Social and Family Affairs
Israel: Ministry of Health
Italy: Ministry of Health
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Lithuania: Ministry of Health
Mexico: Ministry of Health
Netherlands: Medicines Evaluation Board
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Panama: Ministry of Health, Peru: Ministry of Health
Poland: Drug Institut
Portugal: National Institute of Pharmacy and Medicines
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South Africa: Department of Health
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