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Study to Determine Treatment Effects of Denosumab in Patients With Breast Cancer Receiving Aromatase Inhibitor Therapy

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: NCT00556374
Recruitment Status : Active, not recruiting
First Posted : November 12, 2007
Results First Posted : November 6, 2015
Last Update Posted : January 13, 2020
Sponsor:
Collaborator:
Austrian Breast and Colorectal Cancer Study Group
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Supportive Care
Condition Breast Cancer
Interventions Drug: Placebo
Biological: Denosumab
Drug: Non-steroidal aromatase inhibitor therapy
Drug: Zoledronic Acid
Other: Standard of Care
Enrollment 3420
Recruitment Details The first patient was enrolled on 18 December 2006 and the last patient was enrolled on 22 July 2013. 5 patients randomized withdrew full consent and are not included in any analyses. Results data are reported as of 06 October 2014 (the date of last end of treatment visit).
Pre-assignment Details Randomization was stratified by type of hospital (major academic centers or other centers), prior aromatase inhibitor usage (Yes/No) and total lumbar spine bone mineral density (BMD) score at baseline (T-score < -1.0 or ≥ -1.0).
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy. Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Period Title: Overall Study
Started 1709 1711
Received Study Drug 1699 1700
Completed 1462 [1] 1491 [1]
Not Completed 247 220
Reason Not Completed
Withdrawal by Subject             190             172
Death             50             43
Lost to Follow-up             7             5
[1]
Indicates participants continuing study
Arm/Group Title Placebo Denosumab Total
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy. Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy. Total of all reporting groups
Overall Number of Baseline Participants 1709 1711 3420
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1709 participants 1711 participants 3420 participants
64.6  (8.0) 64.0  (7.9) 64.3  (8.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1709 participants 1711 participants 3420 participants
Female
1709
 100.0%
1711
 100.0%
3420
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1709 participants 1711 participants 3420 participants
White/Caucasian
1700
  99.5%
1702
  99.5%
3402
  99.5%
Asian
7
   0.4%
5
   0.3%
12
   0.4%
Hispanic/Latino
1
   0.1%
3
   0.2%
4
   0.1%
Black/Afro-Caribbean
0
   0.0%
1
   0.1%
1
   0.0%
Missing
1
   0.1%
0
   0.0%
1
   0.0%
Stratification Factor: Type of Hospital  
Measure Type: Number
Unit of measure:  Particpants
Number Analyzed 1709 participants 1711 participants 3420 participants
Major Academic Center 632 633 1265
Other Center 1077 1078 2155
Stratification Factor: Prior Aromatase inhibitor Use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1709 participants 1711 participants 3420 participants
No
269
  15.7%
270
  15.8%
539
  15.8%
Yes
1440
  84.3%
1441
  84.2%
2881
  84.2%
Stratification Factor: Total Lumbar Spine Bone Mineral Density T-score  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1709 participants 1711 participants 3420 participants
T-score < -1.0
775
  45.3%
773
  45.2%
1548
  45.3%
T-score ≥ -1.0
934
  54.7%
938
  54.8%
1872
  54.7%
1.Primary Outcome
Title Time to First Clinical Fracture
Hide Description The time to first on-study clinical fracture defined as the number of days from randomization to the date of the x-ray confirming the clinical fracture. A clinical fracture is any clinically evident fracture with associated symptoms and confirmed by x-ray. Participants who died or withdrew without experiencing a clinical fracture were censored at the date of last contact or study termination whichever was earlier.
Time Frame From randomization until the primary analysis cut-off date of 26 March 2014; maximum time on study was 87 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (all randomized participants)
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Overall Number of Participants Analyzed 1709 1711
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not reached due to the low number of events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments The efficacy clinical hypothesis is that denosumab, when administered subcutaneously at a dose of 60 mg every 6 months, will be considered efficacious in patients with non-metastatic breast cancer receiving AIT if the rate of first clinical fracture in denosumab-treated patients is lower than that in placebo-treated patients. It is anticipated that denosumab will reduce the rate by 30% compared with placebo (ie, the true hazard ratio of denosumab compared with placebo is 0.70).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox Proportional Hazard Model
Comments Stratification factors are hospital type, prior use of aromatase inhibitor, and baseline lumbar spine BMD.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.504
Confidence Interval (2-Sided) 95%
0.39 to 0.65
Estimation Comments From the Cox proportional hazard model with treatment as the independent variable and stratified by randomization strata. A hazard ratio < 1.0 indicates a lower average event rate and a longer fracture-free time for denosumab relative to placebo.
2.Secondary Outcome
Title Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites
Hide Description Bone mineral density was assessed by dual x-ray absorptiometry.
Time Frame Baseline and Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
BMD analysis set - total lumbar spine at Month 36 (participants with evaluable BMD values at Baseline and Month 36 for total lumbar spine)
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Overall Number of Participants Analyzed 245 230
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-2.75
(-3.44 to -2.07)
7.27
(6.56 to 7.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Hochberg procedure was used to control for multiplicity.
Method ANCOVA
Comments Model includes treatment group as the independent variable and adjusted for baseline value and the randomization stratification factors.
Method of Estimation Estimation Parameter Difference from Placebo
Estimated Value 10.02
Confidence Interval (2-Sided) 95%
9.04 to 11.01
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites
Hide Description Bone mineral density was assessed by dual x-ray absorptiometry.
Time Frame Baseline and Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
BMD analysis set - total hip at Month 36 (participants with evaluable BMD values at Baseline and Month 36 for total hip)
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Overall Number of Participants Analyzed 237 231
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-3.32
(-4.06 to -2.58)
4.60
(3.85 to 5.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Hochberg procedure was used to control for multiplicity.
Method ANCOVA
Comments Model includes treatment group as the independent variable and adjusted for baseline value and the randomization stratification factors.
Method of Estimation Estimation Parameter Difference from Placebo
Estimated Value 7.92
Confidence Interval (2-Sided) 95%
6.87 to 8.97
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites
Hide Description Bone mineral density was assessed by dual x-ray absorptiometry.
Time Frame Baseline and Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
BMD analysis set - femoral neck at Month 36 (participants with evaluable BMD values at Baseline and Month 36 for femoral neck)
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Overall Number of Participants Analyzed 238 231
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-3.10
(-3.72 to -2.48)
3.41
(2.78 to 4.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Hochberg procedure was used to control for multiplicity.
Method ANCOVA
Comments Model includes treatment group as the independent variable and adjusted for baseline value and the randomization stratification factors.
Method of Estimation Estimation Parameter Difference from Placebo
Estimated Value 6.51
Confidence Interval (2-Sided) 95%
5.62 to 7.39
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With New Vertebral Fractures
Hide Description

Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height.

A new vertebral fracture is defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays.

Time Frame 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
Vertebral Fracture Analysis Set with a Baseline and at least one post-baseline vertebral x-ray prior to or at Month 36.
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Overall Number of Participants Analyzed 809 835
Measure Type: Number
Unit of Measure: participants
49 27
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0088
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model includes treatment groups as the independent variable and stratified by the randomization stratification factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.33 to 0.85
Estimation Comments Values < 1 for odds ratio favor denosumab.
6.Secondary Outcome
Title Number of Participants With New or Worsening Vertebral Fractures
Hide Description Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height. A new vertebral fracture is defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays. Worsening of pre-existing fractures is defined as an increase in fracture severity of at least 1 grade on the semiquantitative scale.
Time Frame 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
Vertebral Fracture Analysis Set with a Baseline and at least one post-baseline vertebral x-ray prior to or at Month 36.
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Overall Number of Participants Analyzed 809 835
Measure Type: Number
Unit of Measure: participants
55 31
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0070
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model includes treatment groups as the independent variable and stratified by the randomization stratification factors.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.34 to 0.84
Estimation Comments Values < 1 for odds ratio favor denosumab.
7.Secondary Outcome
Title Disease-free Survival
Hide Description

Disease-free survival (DFS) is defined as the time interval from the randomization date to the date of first evidence of local or distant metastases, contra-lateral breast cancer, secondary carcinoma, or death from any cause (whichever occurred first). Participants last known to be alive, who did not experience recurrence of disease, were censored at their last contact date or at the data cut-off date whichever came first.

DFS was initially specified to be analyzed after completion of the long-term follow-up period, however after analysis of the primary results was completed the data monitoring committee recommended that the analysis be conducted 18 months after the primary analysis data cut-off date.

Time Frame From randomization until the DFS data cut-off date of 15 September 2015; maximum time on study was 102 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Overall Number of Participants Analyzed 1709 1711
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Not reached due to the low number of events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0515
Comments [Not Specified]
Method Cox Proportional Hazard Model
Comments Stratified by randomization strata (hospital type, use of aromatase inhibitor, baseline lumbar spine BMD).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.816
Confidence Interval (2-Sided) 95%
0.66 to 1.00
Estimation Comments From the Cox Proportional hazard model with treatment fitted as a covariate and stratified by randomization strata. A hazard ratio < 1.0 indicates a lower average event rate and a longer disease-free time for denosumab relative to placebo.
8.Secondary Outcome
Title Bone Metastases-free Survival
Hide Description Bone metastasis-free survival (BMFS) determined by the time from randomization to the first observation of bone metastasis or death from any cause. BMFS will be analyzed after long-term follow-up is complete.
Time Frame Participants will be followed for bone metastasis-free survival once every 12 months for 66 months after primary completion date.
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) determined by the time from randomization to death from any cause. OS will be analyzed after long-term follow-up is complete.
Time Frame Participants will be followed for overall survival once every 12 months for 66 months after primary completion date.
Outcome Measure Data Not Reported
Time Frame From the first dose of study drug until 30 days after the last dose; 0.1 - 7.5 years with median of 3.0 years in Placebo arm, and 0.1 - 7.1 years with median of 3.0 years in Denosumab arm
Adverse Event Reporting Description

Nine participants in the placebo arm received denosumab in error and are counted in this arm for safety analyses.

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

 
Arm/Group Title Placebo Q6M Denosumab 60mg Q6M
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 6 months (Q6M). All participants continued to receive an approved non-steroidal aromatase inhibitor therapy. Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy
All-Cause Mortality
Placebo Q6M Denosumab 60mg Q6M
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Placebo Q6M Denosumab 60mg Q6M
Affected / at Risk (%) Affected / at Risk (%)
Total   515/1690 (30.47%)   521/1709 (30.49%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Anaemia  1  2/1690 (0.12%)  3/1709 (0.18%) 
Iron deficiency anaemia  1  3/1690 (0.18%)  3/1709 (0.18%) 
Leukopenia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Lymphadenitis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Lymphadenopathy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Pancytopenia  1  1/1690 (0.06%)  1/1709 (0.06%) 
Cardiac disorders     
Acute coronary syndrome  1  1/1690 (0.06%)  0/1709 (0.00%) 
Acute left ventricular failure  1  1/1690 (0.06%)  0/1709 (0.00%) 
Acute myocardial infarction  1  1/1690 (0.06%)  1/1709 (0.06%) 
Angina pectoris  1  4/1690 (0.24%)  5/1709 (0.29%) 
Aortic valve incompetence  1  0/1690 (0.00%)  2/1709 (0.12%) 
Aortic valve stenosis  1  2/1690 (0.12%)  4/1709 (0.23%) 
Arrhythmia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Arteriosclerosis coronary artery  1  1/1690 (0.06%)  0/1709 (0.00%) 
Atrial fibrillation  1  11/1690 (0.65%)  14/1709 (0.82%) 
Atrial flutter  1  2/1690 (0.12%)  0/1709 (0.00%) 
Atrial tachycardia  1  1/1690 (0.06%)  1/1709 (0.06%) 
Atrioventricular block second degree  1  1/1690 (0.06%)  0/1709 (0.00%) 
Bradycardia  1  2/1690 (0.12%)  3/1709 (0.18%) 
Cardiac arrest  1  0/1690 (0.00%)  1/1709 (0.06%) 
Cardiac failure  1  1/1690 (0.06%)  8/1709 (0.47%) 
Cardio-respiratory arrest  1  1/1690 (0.06%)  0/1709 (0.00%) 
Cardiomyopathy  1  2/1690 (0.12%)  1/1709 (0.06%) 
Congestive cardiomyopathy  1  1/1690 (0.06%)  2/1709 (0.12%) 
Coronary artery disease  1  11/1690 (0.65%)  10/1709 (0.59%) 
Coronary artery stenosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Ischaemic cardiomyopathy  1  1/1690 (0.06%)  0/1709 (0.00%) 
Mitral valve incompetence  1  1/1690 (0.06%)  2/1709 (0.12%) 
Myocardial infarction  1  5/1690 (0.30%)  1/1709 (0.06%) 
Palpitations  1  1/1690 (0.06%)  0/1709 (0.00%) 
Sick sinus syndrome  1  0/1690 (0.00%)  1/1709 (0.06%) 
Sinus tachycardia  1  2/1690 (0.12%)  0/1709 (0.00%) 
Stress cardiomyopathy  1  1/1690 (0.06%)  0/1709 (0.00%) 
Supraventricular extrasystoles  1  0/1690 (0.00%)  1/1709 (0.06%) 
Supraventricular tachycardia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Tachycardia  1  1/1690 (0.06%)  1/1709 (0.06%) 
Congenital, familial and genetic disorders     
Developmental hip dysplasia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Gene mutation  1  0/1690 (0.00%)  1/1709 (0.06%) 
Ear and labyrinth disorders     
Deafness  1  0/1690 (0.00%)  1/1709 (0.06%) 
Deafness unilateral  1  0/1690 (0.00%)  1/1709 (0.06%) 
Ear canal stenosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Meniere's disease  1  0/1690 (0.00%)  1/1709 (0.06%) 
Sudden hearing loss  1  0/1690 (0.00%)  1/1709 (0.06%) 
Tinnitus  1  0/1690 (0.00%)  1/1709 (0.06%) 
Vertigo  1  10/1690 (0.59%)  9/1709 (0.53%) 
Vertigo positional  1  0/1690 (0.00%)  4/1709 (0.23%) 
Vestibular disorder  1  1/1690 (0.06%)  1/1709 (0.06%) 
Endocrine disorders     
Basedow's disease  1  1/1690 (0.06%)  0/1709 (0.00%) 
Goitre  1  12/1690 (0.71%)  21/1709 (1.23%) 
Hyperparathyroidism  1  0/1690 (0.00%)  2/1709 (0.12%) 
Hyperthyroidism  1  0/1690 (0.00%)  1/1709 (0.06%) 
Eye disorders     
Blepharochalasis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Cataract  1  28/1690 (1.66%)  16/1709 (0.94%) 
Cataract cortical  1  1/1690 (0.06%)  1/1709 (0.06%) 
Cataract nuclear  1  1/1690 (0.06%)  3/1709 (0.18%) 
Diabetic retinopathy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Exfoliation glaucoma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Macular degeneration  1  1/1690 (0.06%)  0/1709 (0.00%) 
Macular fibrosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Open angle glaucoma  1  0/1690 (0.00%)  1/1709 (0.06%) 
Retinal degeneration  1  1/1690 (0.06%)  0/1709 (0.00%) 
Retinal detachment  1  0/1690 (0.00%)  2/1709 (0.12%) 
Retinal tear  1  0/1690 (0.00%)  2/1709 (0.12%) 
Vitreous haemorrhage  1  1/1690 (0.06%)  0/1709 (0.00%) 
Vitreous opacities  1  1/1690 (0.06%)  0/1709 (0.00%) 
Gastrointestinal disorders     
Abdominal adhesions  1  0/1690 (0.00%)  1/1709 (0.06%) 
Abdominal discomfort  1  0/1690 (0.00%)  1/1709 (0.06%) 
Abdominal hernia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Abdominal pain  1  2/1690 (0.12%)  2/1709 (0.12%) 
Abdominal pain upper  1  2/1690 (0.12%)  0/1709 (0.00%) 
Abdominal wall haematoma  1  0/1690 (0.00%)  1/1709 (0.06%) 
Abnormal faeces  1  0/1690 (0.00%)  2/1709 (0.12%) 
Anal fissure  1  0/1690 (0.00%)  1/1709 (0.06%) 
Chronic gastritis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Colitis  1  3/1690 (0.18%)  1/1709 (0.06%) 
Colitis ischaemic  1  0/1690 (0.00%)  2/1709 (0.12%) 
Colon dysplasia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Constipation  1  0/1690 (0.00%)  2/1709 (0.12%) 
Crohn's disease  1  0/1690 (0.00%)  1/1709 (0.06%) 
Dental caries  1  1/1690 (0.06%)  0/1709 (0.00%) 
Diaphragmatic hernia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Diarrhoea  1  4/1690 (0.24%)  2/1709 (0.12%) 
Diverticular perforation  1  1/1690 (0.06%)  1/1709 (0.06%) 
Diverticulum  1  0/1690 (0.00%)  2/1709 (0.12%) 
Diverticulum intestinal  1  2/1690 (0.12%)  1/1709 (0.06%) 
Duodenitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Dysphagia  1  1/1690 (0.06%)  1/1709 (0.06%) 
Enteritis  1  3/1690 (0.18%)  2/1709 (0.12%) 
Gastric antral vascular ectasia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Gastric haemorrhage  1  1/1690 (0.06%)  0/1709 (0.00%) 
Gastritis  1  6/1690 (0.36%)  7/1709 (0.41%) 
Gastritis erosive  1  0/1690 (0.00%)  2/1709 (0.12%) 
Gastritis haemorrhagic  1  1/1690 (0.06%)  0/1709 (0.00%) 
Gastrointestinal angiodysplasia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Gastrointestinal haemorrhage  1  1/1690 (0.06%)  1/1709 (0.06%) 
Gastrointestinal motility disorder  1  0/1690 (0.00%)  1/1709 (0.06%) 
Gastrointestinal necrosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Gastrooesophageal reflux disease  1  2/1690 (0.12%)  1/1709 (0.06%) 
Haematochezia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Haemorrhoids  1  1/1690 (0.06%)  4/1709 (0.23%) 
Hiatus hernia  1  4/1690 (0.24%)  0/1709 (0.00%) 
Ileus  1  1/1690 (0.06%)  2/1709 (0.12%) 
Incarcerated umbilical hernia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Inguinal hernia  1  2/1690 (0.12%)  2/1709 (0.12%) 
Intestinal obstruction  1  0/1690 (0.00%)  1/1709 (0.06%) 
Intestinal perforation  1  0/1690 (0.00%)  1/1709 (0.06%) 
Intestinal polyp  1  1/1690 (0.06%)  0/1709 (0.00%) 
Large intestinal stenosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Large intestine perforation  1  1/1690 (0.06%)  0/1709 (0.00%) 
Large intestine polyp  1  4/1690 (0.24%)  8/1709 (0.47%) 
Mallory-Weiss syndrome  1  0/1690 (0.00%)  1/1709 (0.06%) 
Nausea  1  0/1690 (0.00%)  2/1709 (0.12%) 
Oesophageal motility disorder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Painful defaecation  1  0/1690 (0.00%)  1/1709 (0.06%) 
Pancreatic pseudocyst  1  1/1690 (0.06%)  0/1709 (0.00%) 
Pancreatitis  1  0/1690 (0.00%)  3/1709 (0.18%) 
Pancreatitis acute  1  1/1690 (0.06%)  1/1709 (0.06%) 
Peritoneal necrosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Rectal polyp  1  0/1690 (0.00%)  1/1709 (0.06%) 
Subileus  1  0/1690 (0.00%)  1/1709 (0.06%) 
Swollen tongue  1  0/1690 (0.00%)  1/1709 (0.06%) 
Umbilical hernia  1  2/1690 (0.12%)  4/1709 (0.23%) 
Vomiting  1  2/1690 (0.12%)  0/1709 (0.00%) 
General disorders     
Chest discomfort  1  0/1690 (0.00%)  2/1709 (0.12%) 
Chest pain  1  7/1690 (0.41%)  4/1709 (0.23%) 
Cyst  1  1/1690 (0.06%)  1/1709 (0.06%) 
Device connection issue  1  0/1690 (0.00%)  1/1709 (0.06%) 
Device dislocation  1  4/1690 (0.24%)  3/1709 (0.18%) 
Face oedema  1  1/1690 (0.06%)  0/1709 (0.00%) 
Fat necrosis  1  1/1690 (0.06%)  2/1709 (0.12%) 
Fibrosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
General physical health deterioration  1  1/1690 (0.06%)  3/1709 (0.18%) 
Granuloma  1  0/1690 (0.00%)  1/1709 (0.06%) 
Hyperplasia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Impaired healing  1  0/1690 (0.00%)  4/1709 (0.23%) 
Incarcerated hernia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Local swelling  1  1/1690 (0.06%)  0/1709 (0.00%) 
Medical device complication  1  1/1690 (0.06%)  1/1709 (0.06%) 
Multi-organ failure  1  1/1690 (0.06%)  0/1709 (0.00%) 
Non-cardiac chest pain  1  2/1690 (0.12%)  1/1709 (0.06%) 
Oedema peripheral  1  2/1690 (0.12%)  3/1709 (0.18%) 
Pain  1  2/1690 (0.12%)  2/1709 (0.12%) 
Pyrexia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  1/1690 (0.06%)  1/1709 (0.06%) 
Biliary cirrhosis primary  1  1/1690 (0.06%)  0/1709 (0.00%) 
Biliary colic  1  1/1690 (0.06%)  1/1709 (0.06%) 
Cholangitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Cholecystitis  1  2/1690 (0.12%)  8/1709 (0.47%) 
Cholecystitis acute  1  1/1690 (0.06%)  0/1709 (0.00%) 
Cholecystitis chronic  1  3/1690 (0.18%)  2/1709 (0.12%) 
Cholelithiasis  1  9/1690 (0.53%)  14/1709 (0.82%) 
Drug-induced liver injury  1  1/1690 (0.06%)  0/1709 (0.00%) 
Gallbladder polyp  1  2/1690 (0.12%)  0/1709 (0.00%) 
Hepatic cirrhosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Jaundice  1  0/1690 (0.00%)  1/1709 (0.06%) 
Immune system disorders     
Allergy to arthropod sting  1  1/1690 (0.06%)  0/1709 (0.00%) 
Anaphylactic reaction  1  0/1690 (0.00%)  1/1709 (0.06%) 
Drug hypersensitivity  1  1/1690 (0.06%)  0/1709 (0.00%) 
Hypersensitivity  1  2/1690 (0.12%)  2/1709 (0.12%) 
Sarcoidosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Infections and infestations     
Abscess  1  0/1690 (0.00%)  1/1709 (0.06%) 
Abscess jaw  1  0/1690 (0.00%)  1/1709 (0.06%) 
Abscess limb  1  0/1690 (0.00%)  1/1709 (0.06%) 
Anal abscess  1  0/1690 (0.00%)  1/1709 (0.06%) 
Appendicitis  1  2/1690 (0.12%)  5/1709 (0.29%) 
Arthritis infective  1  1/1690 (0.06%)  0/1709 (0.00%) 
Bacterial infection  1  1/1690 (0.06%)  0/1709 (0.00%) 
Borrelia infection  1  2/1690 (0.12%)  0/1709 (0.00%) 
Breast abscess  1  1/1690 (0.06%)  2/1709 (0.12%) 
Bronchitis  1  1/1690 (0.06%)  6/1709 (0.35%) 
Bronchopneumonia  1  1/1690 (0.06%)  2/1709 (0.12%) 
Campylobacter gastroenteritis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Cellulitis  1  2/1690 (0.12%)  0/1709 (0.00%) 
Cholecystitis infective  1  1/1690 (0.06%)  0/1709 (0.00%) 
Chronic sinusitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Clostridium difficile colitis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Cystitis  1  2/1690 (0.12%)  0/1709 (0.00%) 
Device related infection  1  3/1690 (0.18%)  2/1709 (0.12%) 
Diverticulitis  1  9/1690 (0.53%)  9/1709 (0.53%) 
Encephalitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Erysipelas  1  10/1690 (0.59%)  15/1709 (0.88%) 
Escherichia sepsis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Escherichia urinary tract infection  1  1/1690 (0.06%)  0/1709 (0.00%) 
Eye infection bacterial  1  0/1690 (0.00%)  1/1709 (0.06%) 
Febrile infection  1  2/1690 (0.12%)  1/1709 (0.06%) 
Gastroenteritis  1  1/1690 (0.06%)  6/1709 (0.35%) 
Gastrointestinal infection  1  1/1690 (0.06%)  0/1709 (0.00%) 
Haematoma infection  1  2/1690 (0.12%)  0/1709 (0.00%) 
Helicobacter gastritis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Herpes zoster  1  3/1690 (0.18%)  2/1709 (0.12%) 
Implant site infection  1  0/1690 (0.00%)  1/1709 (0.06%) 
Incision site abscess  1  0/1690 (0.00%)  1/1709 (0.06%) 
Infected seroma  1  0/1690 (0.00%)  1/1709 (0.06%) 
Infection  1  2/1690 (0.12%)  0/1709 (0.00%) 
Infective exacerbation of chronic obstructive airways disease  1  1/1690 (0.06%)  1/1709 (0.06%) 
Influenza  1  1/1690 (0.06%)  0/1709 (0.00%) 
Joint abscess  1  1/1690 (0.06%)  0/1709 (0.00%) 
Localised infection  1  0/1690 (0.00%)  1/1709 (0.06%) 
Mastitis  1  1/1690 (0.06%)  2/1709 (0.12%) 
Nasopharyngitis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Oesophageal candidiasis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Ophthalmic herpes zoster  1  0/1690 (0.00%)  1/1709 (0.06%) 
Otitis media  1  1/1690 (0.06%)  0/1709 (0.00%) 
Paronychia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Peritoneal abscess  1  1/1690 (0.06%)  0/1709 (0.00%) 
Pharyngitis  1  0/1690 (0.00%)  3/1709 (0.18%) 
Pneumonia  1  7/1690 (0.41%)  9/1709 (0.53%) 
Pneumonia bacterial  1  1/1690 (0.06%)  0/1709 (0.00%) 
Post procedural infection  1  0/1690 (0.00%)  2/1709 (0.12%) 
Postoperative wound infection  1  2/1690 (0.12%)  0/1709 (0.00%) 
Psoas abscess  1  0/1690 (0.00%)  1/1709 (0.06%) 
Pyelonephritis  1  2/1690 (0.12%)  3/1709 (0.18%) 
Respiratory tract infection  1  1/1690 (0.06%)  4/1709 (0.23%) 
Rhinitis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Salpingitis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Sepsis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Sinusitis  1  1/1690 (0.06%)  4/1709 (0.23%) 
Skin infection  1  1/1690 (0.06%)  0/1709 (0.00%) 
Soft tissue infection  1  1/1690 (0.06%)  0/1709 (0.00%) 
Subcutaneous abscess  1  3/1690 (0.18%)  6/1709 (0.35%) 
Tonsillitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Tracheobronchitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Urinary tract infection  1  9/1690 (0.53%)  7/1709 (0.41%) 
Vestibular neuronitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Injury, poisoning and procedural complications     
Alcohol poisoning  1  1/1690 (0.06%)  1/1709 (0.06%) 
Anastomotic stenosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Animal bite  1  1/1690 (0.06%)  0/1709 (0.00%) 
Bone contusion  1  2/1690 (0.12%)  0/1709 (0.00%) 
Brain contusion  1  0/1690 (0.00%)  1/1709 (0.06%) 
Bursa injury  1  0/1690 (0.00%)  1/1709 (0.06%) 
Concussion  1  5/1690 (0.30%)  1/1709 (0.06%) 
Contusion  1  6/1690 (0.36%)  4/1709 (0.23%) 
Extradural haematoma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Fall  1  1/1690 (0.06%)  0/1709 (0.00%) 
Haemodilution  1  0/1690 (0.00%)  1/1709 (0.06%) 
Head injury  1  1/1690 (0.06%)  0/1709 (0.00%) 
Incisional hernia  1  3/1690 (0.18%)  3/1709 (0.18%) 
Joint dislocation  1  3/1690 (0.18%)  2/1709 (0.12%) 
Joint injury  1  1/1690 (0.06%)  0/1709 (0.00%) 
Ligament rupture  1  3/1690 (0.18%)  0/1709 (0.00%) 
Ligament sprain  1  2/1690 (0.12%)  0/1709 (0.00%) 
Meniscus injury  1  24/1690 (1.42%)  23/1709 (1.35%) 
Post procedural bile leak  1  0/1690 (0.00%)  1/1709 (0.06%) 
Post procedural complication  1  2/1690 (0.12%)  1/1709 (0.06%) 
Post procedural haematoma  1  1/1690 (0.06%)  2/1709 (0.12%) 
Post procedural inflammation  1  1/1690 (0.06%)  0/1709 (0.00%) 
Post-traumatic neck syndrome  1  0/1690 (0.00%)  1/1709 (0.06%) 
Postoperative hernia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Postoperative thrombosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Procedural intestinal perforation  1  0/1690 (0.00%)  1/1709 (0.06%) 
Procedural pain  1  0/1690 (0.00%)  2/1709 (0.12%) 
Radiation alveolitis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Radiation pneumonitis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Radiation skin injury  1  1/1690 (0.06%)  4/1709 (0.23%) 
Road traffic accident  1  0/1690 (0.00%)  1/1709 (0.06%) 
Scar  1  5/1690 (0.30%)  2/1709 (0.12%) 
Seroma  1  2/1690 (0.12%)  2/1709 (0.12%) 
Skin abrasion  1  0/1690 (0.00%)  1/1709 (0.06%) 
Spinal column injury  1  1/1690 (0.06%)  0/1709 (0.00%) 
Splenic haematoma  1  0/1690 (0.00%)  1/1709 (0.06%) 
Subdural haematoma  1  4/1690 (0.24%)  0/1709 (0.00%) 
Suture rupture  1  1/1690 (0.06%)  0/1709 (0.00%) 
Tendon rupture  1  1/1690 (0.06%)  1/1709 (0.06%) 
Toxicity to various agents  1  1/1690 (0.06%)  1/1709 (0.06%) 
Traumatic arthrosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Vascular bypass dysfunction  1  0/1690 (0.00%)  1/1709 (0.06%) 
Wound  1  1/1690 (0.06%)  0/1709 (0.00%) 
Wound dehiscence  1  1/1690 (0.06%)  1/1709 (0.06%) 
Investigations     
Blood creatinine increased  1  0/1690 (0.00%)  1/1709 (0.06%) 
Blood pressure abnormal  1  0/1690 (0.00%)  1/1709 (0.06%) 
Colonoscopy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Glycosylated haemoglobin increased  1  0/1690 (0.00%)  1/1709 (0.06%) 
Mammogram abnormal  1  0/1690 (0.00%)  1/1709 (0.06%) 
Pulmonary arterial pressure increased  1  1/1690 (0.06%)  0/1709 (0.00%) 
Smear cervix abnormal  1  1/1690 (0.06%)  0/1709 (0.00%) 
Weight decreased  1  0/1690 (0.00%)  1/1709 (0.06%) 
Metabolism and nutrition disorders     
Dehydration  1  0/1690 (0.00%)  1/1709 (0.06%) 
Diabetes mellitus  1  0/1690 (0.00%)  1/1709 (0.06%) 
Electrolyte imbalance  1  0/1690 (0.00%)  2/1709 (0.12%) 
Hyperglycaemia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Hypocalcaemia  1  1/1690 (0.06%)  2/1709 (0.12%) 
Hyponatraemia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Insulin resistance  1  1/1690 (0.06%)  0/1709 (0.00%) 
Obesity  1  1/1690 (0.06%)  0/1709 (0.00%) 
Type 2 diabetes mellitus  1  1/1690 (0.06%)  3/1709 (0.18%) 
Musculoskeletal and connective tissue disorders     
Acquired claw toe  1  1/1690 (0.06%)  0/1709 (0.00%) 
Arthralgia  1  2/1690 (0.12%)  6/1709 (0.35%) 
Arthritis  1  4/1690 (0.24%)  0/1709 (0.00%) 
Back pain  1  8/1690 (0.47%)  10/1709 (0.59%) 
Bone cyst  1  0/1690 (0.00%)  1/1709 (0.06%) 
Bone pain  1  0/1690 (0.00%)  1/1709 (0.06%) 
Bursitis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Cervical spinal stenosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Chondromalacia  1  2/1690 (0.12%)  0/1709 (0.00%) 
Chondropathy  1  1/1690 (0.06%)  6/1709 (0.35%) 
Dupuytren's contracture  1  2/1690 (0.12%)  0/1709 (0.00%) 
Exostosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Fistula  1  2/1690 (0.12%)  0/1709 (0.00%) 
Foot deformity  1  12/1690 (0.71%)  13/1709 (0.76%) 
Haemarthrosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Intervertebral disc degeneration  1  0/1690 (0.00%)  1/1709 (0.06%) 
Intervertebral disc disorder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Intervertebral disc protrusion  1  15/1690 (0.89%)  14/1709 (0.82%) 
Joint effusion  1  1/1690 (0.06%)  0/1709 (0.00%) 
Joint instability  1  0/1690 (0.00%)  1/1709 (0.06%) 
Ligament disorder  1  1/1690 (0.06%)  1/1709 (0.06%) 
Lumbar spinal stenosis  1  6/1690 (0.36%)  8/1709 (0.47%) 
Meniscal degeneration  1  2/1690 (0.12%)  0/1709 (0.00%) 
Mobility decreased  1  0/1690 (0.00%)  1/1709 (0.06%) 
Musculoskeletal chest pain  1  1/1690 (0.06%)  1/1709 (0.06%) 
Musculoskeletal pain  1  1/1690 (0.06%)  1/1709 (0.06%) 
Osteoarthritis  1  58/1690 (3.43%)  62/1709 (3.63%) 
Osteochondrosis  1  1/1690 (0.06%)  2/1709 (0.12%) 
Osteonecrosis  1  3/1690 (0.18%)  1/1709 (0.06%) 
Pain in extremity  1  0/1690 (0.00%)  2/1709 (0.12%) 
Polyarthritis  1  1/1690 (0.06%)  4/1709 (0.23%) 
Polymyalgia rheumatica  1  1/1690 (0.06%)  0/1709 (0.00%) 
Pseudarthrosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Rheumatoid arthritis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Rotator cuff syndrome  1  1/1690 (0.06%)  3/1709 (0.18%) 
Scoliosis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Spinal column stenosis  1  1/1690 (0.06%)  3/1709 (0.18%) 
Spinal osteoarthritis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Spinal pain  1  3/1690 (0.18%)  2/1709 (0.12%) 
Spondyloarthropathy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Spondylolisthesis  1  2/1690 (0.12%)  1/1709 (0.06%) 
Synovitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Tendon disorder  1  0/1690 (0.00%)  3/1709 (0.18%) 
Tenosynovitis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Tenosynovitis stenosans  1  4/1690 (0.24%)  9/1709 (0.53%) 
Torticollis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Trigger finger  1  6/1690 (0.36%)  2/1709 (0.12%) 
Vertebral foraminal stenosis  1  1/1690 (0.06%)  4/1709 (0.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of colon  1  0/1690 (0.00%)  1/1709 (0.06%) 
Basal cell carcinoma  1  5/1690 (0.30%)  4/1709 (0.23%) 
Benign breast neoplasm  1  0/1690 (0.00%)  2/1709 (0.12%) 
Benign lymph node neoplasm  1  0/1690 (0.00%)  1/1709 (0.06%) 
Benign salivary gland neoplasm  1  1/1690 (0.06%)  1/1709 (0.06%) 
Bladder papilloma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Bladder transitional cell carcinoma recurrent  1  1/1690 (0.06%)  0/1709 (0.00%) 
Bowen's disease  1  0/1690 (0.00%)  1/1709 (0.06%) 
Breast adenoma  1  1/1690 (0.06%)  1/1709 (0.06%) 
Breast cancer  1  0/1690 (0.00%)  1/1709 (0.06%) 
Breast cancer metastatic  1  1/1690 (0.06%)  0/1709 (0.00%) 
Breast cancer recurrent  1  4/1690 (0.24%)  3/1709 (0.18%) 
Breast cancer stage III  1  0/1690 (0.00%)  1/1709 (0.06%) 
Bronchial carcinoma  1  1/1690 (0.06%)  3/1709 (0.18%) 
Cervix carcinoma  1  0/1690 (0.00%)  1/1709 (0.06%) 
Chronic lymphocytic leukaemia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Colon adenoma  1  1/1690 (0.06%)  3/1709 (0.18%) 
Colon cancer  1  1/1690 (0.06%)  2/1709 (0.12%) 
Colon neoplasm  1  2/1690 (0.12%)  0/1709 (0.00%) 
Contralateral breast cancer  1  1/1690 (0.06%)  4/1709 (0.23%) 
Endometrial adenocarcinoma  1  1/1690 (0.06%)  1/1709 (0.06%) 
Fibroadenoma of breast  1  1/1690 (0.06%)  1/1709 (0.06%) 
Gastric cancer  1  1/1690 (0.06%)  0/1709 (0.00%) 
Gastrointestinal tract adenoma  1  1/1690 (0.06%)  2/1709 (0.12%) 
Haemangioma of liver  1  1/1690 (0.06%)  0/1709 (0.00%) 
Hepatic neoplasm  1  0/1690 (0.00%)  1/1709 (0.06%) 
Inflammatory myofibroblastic tumour  1  1/1690 (0.06%)  0/1709 (0.00%) 
Intestinal adenocarcinoma  1  1/1690 (0.06%)  1/1709 (0.06%) 
Intraductal papilloma of breast  1  1/1690 (0.06%)  0/1709 (0.00%) 
Intraductal proliferative breast lesion  1  4/1690 (0.24%)  1/1709 (0.06%) 
Invasive ductal breast carcinoma  1  0/1690 (0.00%)  2/1709 (0.12%) 
Lentigo maligna  1  1/1690 (0.06%)  0/1709 (0.00%) 
Lip and/or oral cavity cancer  1  1/1690 (0.06%)  0/1709 (0.00%) 
Lipoma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Lobular breast carcinoma in situ  1  1/1690 (0.06%)  0/1709 (0.00%) 
Lung adenocarcinoma  1  1/1690 (0.06%)  2/1709 (0.12%) 
Lung neoplasm malignant  1  2/1690 (0.12%)  0/1709 (0.00%) 
Malignant melanoma  1  1/1690 (0.06%)  1/1709 (0.06%) 
Malignant melanoma in situ  1  1/1690 (0.06%)  0/1709 (0.00%) 
Malignant pleural effusion  1  0/1690 (0.00%)  1/1709 (0.06%) 
Mediastinum neoplasm  1  0/1690 (0.00%)  1/1709 (0.06%) 
Melanocytic naevus  1  1/1690 (0.06%)  0/1709 (0.00%) 
Meningioma  1  2/1690 (0.12%)  1/1709 (0.06%) 
Meningioma benign  1  0/1690 (0.00%)  1/1709 (0.06%) 
Metastases to bone  1  5/1690 (0.30%)  5/1709 (0.29%) 
Metastases to liver  1  3/1690 (0.18%)  2/1709 (0.12%) 
Metastases to lung  1  0/1690 (0.00%)  1/1709 (0.06%) 
Metastases to lymph nodes  1  1/1690 (0.06%)  2/1709 (0.12%) 
Metastases to peritoneum  1  1/1690 (0.06%)  1/1709 (0.06%) 
Metastases to pleura  1  0/1690 (0.00%)  1/1709 (0.06%) 
Metastases to skin  1  1/1690 (0.06%)  0/1709 (0.00%) 
Neuroma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Oral fibroma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Ovarian adenoma  1  0/1690 (0.00%)  4/1709 (0.23%) 
Ovarian epithelial cancer  1  1/1690 (0.06%)  0/1709 (0.00%) 
Ovarian fibroma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Pancreatic carcinoma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Papillary thyroid cancer  1  1/1690 (0.06%)  1/1709 (0.06%) 
Parathyroid tumour benign  1  2/1690 (0.12%)  0/1709 (0.00%) 
Pituitary tumour benign  1  0/1690 (0.00%)  1/1709 (0.06%) 
Rectal adenocarcinoma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Rectal adenoma  1  3/1690 (0.18%)  0/1709 (0.00%) 
Rectal cancer  1  1/1690 (0.06%)  3/1709 (0.18%) 
Renal cell carcinoma  1  1/1690 (0.06%)  1/1709 (0.06%) 
Salivary gland adenoma  1  0/1690 (0.00%)  2/1709 (0.12%) 
Schwannoma  1  0/1690 (0.00%)  1/1709 (0.06%) 
Squamous cell carcinoma  1  3/1690 (0.18%)  0/1709 (0.00%) 
Squamous cell carcinoma of lung  1  1/1690 (0.06%)  0/1709 (0.00%) 
Thyroid adenoma  1  0/1690 (0.00%)  1/1709 (0.06%) 
Thyroid cancer  1  1/1690 (0.06%)  1/1709 (0.06%) 
Thyroid neoplasm  1  2/1690 (0.12%)  1/1709 (0.06%) 
Transitional cell carcinoma  1  0/1690 (0.00%)  2/1709 (0.12%) 
Transitional cell carcinoma urethra  1  1/1690 (0.06%)  0/1709 (0.00%) 
Uterine leiomyoma  1  3/1690 (0.18%)  0/1709 (0.00%) 
Uterine leiomyosarcoma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Nervous system disorders     
Acoustic neuritis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Amnesia  1  1/1690 (0.06%)  1/1709 (0.06%) 
Amnestic disorder  1  0/1690 (0.00%)  1/1709 (0.06%) 
Carotid artery aneurysm  1  2/1690 (0.12%)  0/1709 (0.00%) 
Carotid artery disease  1  0/1690 (0.00%)  1/1709 (0.06%) 
Carotid artery stenosis  1  2/1690 (0.12%)  1/1709 (0.06%) 
Carpal tunnel syndrome  1  13/1690 (0.77%)  14/1709 (0.82%) 
Cerebellar haemorrhage  1  0/1690 (0.00%)  1/1709 (0.06%) 
Cerebral infarction  1  1/1690 (0.06%)  1/1709 (0.06%) 
Cerebral ischaemia  1  1/1690 (0.06%)  1/1709 (0.06%) 
Cerebrovascular accident  1  9/1690 (0.53%)  6/1709 (0.35%) 
Cerebrovascular disorder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Cervical myelopathy  1  1/1690 (0.06%)  0/1709 (0.00%) 
Cervical radiculopathy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Cervicobrachial syndrome  1  2/1690 (0.12%)  3/1709 (0.18%) 
Chronic inflammatory demyelinating polyradiculoneuropathy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Cognitive disorder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Dementia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Diabetic coma  1  1/1690 (0.06%)  0/1709 (0.00%) 
Dizziness  1  2/1690 (0.12%)  0/1709 (0.00%) 
Drop attacks  1  0/1690 (0.00%)  1/1709 (0.06%) 
Epilepsy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Facial neuralgia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Facial paresis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Generalised tonic-clonic seizure  1  1/1690 (0.06%)  0/1709 (0.00%) 
Guillain-Barre syndrome  1  1/1690 (0.06%)  0/1709 (0.00%) 
Headache  1  0/1690 (0.00%)  2/1709 (0.12%) 
Intercostal neuralgia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Intracranial aneurysm  1  1/1690 (0.06%)  0/1709 (0.00%) 
Loss of consciousness  1  0/1690 (0.00%)  1/1709 (0.06%) 
Lumbar radiculopathy  1  0/1690 (0.00%)  2/1709 (0.12%) 
Medication overuse headache  1  0/1690 (0.00%)  1/1709 (0.06%) 
Meralgia paraesthetica  1  1/1690 (0.06%)  0/1709 (0.00%) 
Migraine  1  0/1690 (0.00%)  1/1709 (0.06%) 
Monoplegia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Morton's neuralgia  1  1/1690 (0.06%)  1/1709 (0.06%) 
Motor neurone disease  1  1/1690 (0.06%)  0/1709 (0.00%) 
Nerve compression  1  0/1690 (0.00%)  1/1709 (0.06%) 
Nervous system disorder  1  0/1690 (0.00%)  1/1709 (0.06%) 
Neuralgia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Paraesthesia  1  0/1690 (0.00%)  2/1709 (0.12%) 
Peroneal nerve palsy  1  1/1690 (0.06%)  0/1709 (0.00%) 
Polyneuropathy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Radicular syndrome  1  1/1690 (0.06%)  2/1709 (0.12%) 
Sciatica  1  4/1690 (0.24%)  7/1709 (0.41%) 
Senile dementia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Small fibre neuropathy  1  1/1690 (0.06%)  0/1709 (0.00%) 
Speech disorder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Spinal claudication  1  0/1690 (0.00%)  2/1709 (0.12%) 
Syncope  1  4/1690 (0.24%)  6/1709 (0.35%) 
Transient global amnesia  1  0/1690 (0.00%)  3/1709 (0.18%) 
Transient ischaemic attack  1  1/1690 (0.06%)  1/1709 (0.06%) 
VIIth nerve paralysis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Vascular encephalopathy  1  0/1690 (0.00%)  2/1709 (0.12%) 
Psychiatric disorders     
Alcohol withdrawal syndrome  1  0/1690 (0.00%)  2/1709 (0.12%) 
Bipolar disorder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Burnout syndrome  1  0/1690 (0.00%)  1/1709 (0.06%) 
Depressed mood  1  0/1690 (0.00%)  1/1709 (0.06%) 
Depression  1  8/1690 (0.47%)  8/1709 (0.47%) 
Mental disorder  1  1/1690 (0.06%)  1/1709 (0.06%) 
Panic attack  1  2/1690 (0.12%)  0/1709 (0.00%) 
Post-traumatic stress disorder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Psychosomatic disease  1  1/1690 (0.06%)  0/1709 (0.00%) 
Stress  1  0/1690 (0.00%)  1/1709 (0.06%) 
Suicide attempt  1  1/1690 (0.06%)  0/1709 (0.00%) 
Renal and urinary disorders     
Acute prerenal failure  1  0/1690 (0.00%)  1/1709 (0.06%) 
Calculus ureteric  1  2/1690 (0.12%)  1/1709 (0.06%) 
Cystitis haemorrhagic  1  1/1690 (0.06%)  1/1709 (0.06%) 
Diabetic nephropathy  1  1/1690 (0.06%)  0/1709 (0.00%) 
Hydronephrosis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Hypertonic bladder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Incontinence  1  2/1690 (0.12%)  1/1709 (0.06%) 
Nephrolithiasis  1  2/1690 (0.12%)  0/1709 (0.00%) 
Renal artery stenosis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Renal colic  1  2/1690 (0.12%)  0/1709 (0.00%) 
Renal failure acute  1  1/1690 (0.06%)  1/1709 (0.06%) 
Stress urinary incontinence  1  1/1690 (0.06%)  4/1709 (0.23%) 
Urethral disorder  1  1/1690 (0.06%)  0/1709 (0.00%) 
Urge incontinence  1  2/1690 (0.12%)  1/1709 (0.06%) 
Urinary incontinence  1  0/1690 (0.00%)  1/1709 (0.06%) 
Reproductive system and breast disorders     
Adenomyosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Adnexa uteri cyst  1  0/1690 (0.00%)  2/1709 (0.12%) 
Adnexa uteri mass  1  1/1690 (0.06%)  0/1709 (0.00%) 
Breast calcifications  1  4/1690 (0.24%)  4/1709 (0.23%) 
Breast cyst  1  1/1690 (0.06%)  1/1709 (0.06%) 
Breast discharge  1  1/1690 (0.06%)  0/1709 (0.00%) 
Breast disorder  1  6/1690 (0.36%)  1/1709 (0.06%) 
Breast enlargement  1  1/1690 (0.06%)  0/1709 (0.00%) 
Breast fibrosis  1  3/1690 (0.18%)  2/1709 (0.12%) 
Breast haematoma  1  2/1690 (0.12%)  1/1709 (0.06%) 
Breast necrosis  1  1/1690 (0.06%)  3/1709 (0.18%) 
Breast pain  1  1/1690 (0.06%)  0/1709 (0.00%) 
Cervical dysplasia  1  1/1690 (0.06%)  4/1709 (0.23%) 
Cervical polyp  1  0/1690 (0.00%)  3/1709 (0.18%) 
Cystocele  1  2/1690 (0.12%)  0/1709 (0.00%) 
Dyspareunia  1  0/1690 (0.00%)  1/1709 (0.06%) 
Endometrial hyperplasia  1  2/1690 (0.12%)  3/1709 (0.18%) 
Fibrocystic breast disease  1  0/1690 (0.00%)  3/1709 (0.18%) 
Ovarian cyst  1  1/1690 (0.06%)  7/1709 (0.41%) 
Postmenopausal haemorrhage  1  1/1690 (0.06%)  3/1709 (0.18%) 
Rectocele  1  2/1690 (0.12%)  0/1709 (0.00%) 
Uterine adhesions  1  0/1690 (0.00%)  1/1709 (0.06%) 
Uterine polyp  1  3/1690 (0.18%)  4/1709 (0.23%) 
Uterine prolapse  1  2/1690 (0.12%)  1/1709 (0.06%) 
Uterovaginal prolapse  1  2/1690 (0.12%)  2/1709 (0.12%) 
Vaginal prolapse  1  0/1690 (0.00%)  1/1709 (0.06%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  2/1690 (0.12%)  0/1709 (0.00%) 
Atelectasis  1  0/1690 (0.00%)  2/1709 (0.12%) 
Cheyne-Stokes respiration  1  0/1690 (0.00%)  1/1709 (0.06%) 
Chronic obstructive pulmonary disease  1  0/1690 (0.00%)  3/1709 (0.18%) 
Cough  1  1/1690 (0.06%)  1/1709 (0.06%) 
Diaphragmatic paralysis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Dyspnoea  1  4/1690 (0.24%)  3/1709 (0.18%) 
Dyspnoea exertional  1  0/1690 (0.00%)  4/1709 (0.23%) 
Emphysema  1  0/1690 (0.00%)  1/1709 (0.06%) 
Epistaxis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Hyperventilation  1  0/1690 (0.00%)  1/1709 (0.06%) 
Lung disorder  1  0/1690 (0.00%)  1/1709 (0.06%) 
Nasal polyps  1  0/1690 (0.00%)  1/1709 (0.06%) 
Organising pneumonia  1  1/1690 (0.06%)  0/1709 (0.00%) 
Oropharyngeal pain  1  0/1690 (0.00%)  1/1709 (0.06%) 
Pharyngeal cyst  1  1/1690 (0.06%)  0/1709 (0.00%) 
Pleural effusion  1  2/1690 (0.12%)  1/1709 (0.06%) 
Pleurisy  1  0/1690 (0.00%)  2/1709 (0.12%) 
Pneumonia aspiration  1  2/1690 (0.12%)  0/1709 (0.00%) 
Pneumonitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Pneumothorax  1  1/1690 (0.06%)  0/1709 (0.00%) 
Pulmonary alveolar haemorrhage  1  1/1690 (0.06%)  0/1709 (0.00%) 
Pulmonary embolism  1  11/1690 (0.65%)  12/1709 (0.70%) 
Pulmonary fibrosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Pulmonary hypertension  1  0/1690 (0.00%)  1/1709 (0.06%) 
Pulmonary mass  1  2/1690 (0.12%)  0/1709 (0.00%) 
Pulmonary oedema  1  1/1690 (0.06%)  0/1709 (0.00%) 
Sinus polyp  1  0/1690 (0.00%)  1/1709 (0.06%) 
Sleep apnoea syndrome  1  5/1690 (0.30%)  2/1709 (0.12%) 
Vocal cord polyp  1  2/1690 (0.12%)  0/1709 (0.00%) 
Skin and subcutaneous tissue disorders     
Acquired epidermolysis bullosa  1  0/1690 (0.00%)  1/1709 (0.06%) 
Angioedema  1  0/1690 (0.00%)  1/1709 (0.06%) 
Dermal cyst  1  0/1690 (0.00%)  1/1709 (0.06%) 
Dermatitis allergic  1  0/1690 (0.00%)  2/1709 (0.12%) 
Diabetic foot  1  0/1690 (0.00%)  1/1709 (0.06%) 
Drug eruption  1  2/1690 (0.12%)  0/1709 (0.00%) 
Eczema  1  0/1690 (0.00%)  1/1709 (0.06%) 
Erythema  1  0/1690 (0.00%)  1/1709 (0.06%) 
Erythema nodosum  1  0/1690 (0.00%)  1/1709 (0.06%) 
Hyperkeratosis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Keloid scar  1  0/1690 (0.00%)  2/1709 (0.12%) 
Lichen sclerosus  1  0/1690 (0.00%)  1/1709 (0.06%) 
Panniculitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Rash  1  0/1690 (0.00%)  1/1709 (0.06%) 
Rash maculo-papular  1  0/1690 (0.00%)  1/1709 (0.06%) 
Scar pain  1  1/1690 (0.06%)  2/1709 (0.12%) 
Skin necrosis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Skin ulcer  1  1/1690 (0.06%)  3/1709 (0.18%) 
Stasis dermatitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Urticaria  1  1/1690 (0.06%)  1/1709 (0.06%) 
Surgical and medical procedures     
Breast reconstruction  1  0/1690 (0.00%)  1/1709 (0.06%) 
Hysterectomy  1  1/1690 (0.06%)  0/1709 (0.00%) 
Hysterosalpingo-oophorectomy  1  0/1690 (0.00%)  1/1709 (0.06%) 
Intraocular lens implant  1  0/1690 (0.00%)  1/1709 (0.06%) 
Knee arthroplasty  1  1/1690 (0.06%)  0/1709 (0.00%) 
Mastectomy  1  3/1690 (0.18%)  1/1709 (0.06%) 
Oophorectomy  1  1/1690 (0.06%)  0/1709 (0.00%) 
Prophylaxis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Vascular disorders     
Aortic dissection  1  0/1690 (0.00%)  1/1709 (0.06%) 
Arterial stenosis  1  2/1690 (0.12%)  0/1709 (0.00%) 
Arteriovenous fistula  1  0/1690 (0.00%)  1/1709 (0.06%) 
Bleeding varicose vein  1  1/1690 (0.06%)  1/1709 (0.06%) 
Circulatory collapse  1  4/1690 (0.24%)  3/1709 (0.18%) 
Deep vein thrombosis  1  3/1690 (0.18%)  2/1709 (0.12%) 
Femoral artery occlusion  1  1/1690 (0.06%)  2/1709 (0.12%) 
Haematoma  1  3/1690 (0.18%)  0/1709 (0.00%) 
Hypertension  1  6/1690 (0.36%)  5/1709 (0.29%) 
Hypertensive crisis  1  14/1690 (0.83%)  10/1709 (0.59%) 
Hypotension  1  2/1690 (0.12%)  0/1709 (0.00%) 
Iliac artery occlusion  1  0/1690 (0.00%)  1/1709 (0.06%) 
Intermittent claudication  1  0/1690 (0.00%)  1/1709 (0.06%) 
Lymphoedema  1  2/1690 (0.12%)  5/1709 (0.29%) 
Peripheral arterial occlusive disease  1  4/1690 (0.24%)  3/1709 (0.18%) 
Peripheral artery stenosis  1  1/1690 (0.06%)  3/1709 (0.18%) 
Peripheral venous disease  1  4/1690 (0.24%)  0/1709 (0.00%) 
Raynaud's phenomenon  1  1/1690 (0.06%)  0/1709 (0.00%) 
Subclavian artery stenosis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Subclavian steal syndrome  1  1/1690 (0.06%)  0/1709 (0.00%) 
Temporal arteritis  1  0/1690 (0.00%)  2/1709 (0.12%) 
Thrombophlebitis  1  0/1690 (0.00%)  1/1709 (0.06%) 
Thrombosis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Varicose vein  1  10/1690 (0.59%)  12/1709 (0.70%) 
Vasculitis  1  1/1690 (0.06%)  0/1709 (0.00%) 
Venous thrombosis  1  1/1690 (0.06%)  1/1709 (0.06%) 
Venous thrombosis limb  1  0/1690 (0.00%)  1/1709 (0.06%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Q6M Denosumab 60mg Q6M
Affected / at Risk (%) Affected / at Risk (%)
Total   838/1690 (49.59%)   882/1709 (51.61%) 
General disorders     
Fatigue  1  100/1690 (5.92%)  109/1709 (6.38%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  446/1690 (26.39%)  441/1709 (25.80%) 
Back pain  1  146/1690 (8.64%)  151/1709 (8.84%) 
Bone pain  1  111/1690 (6.57%)  139/1709 (8.13%) 
Osteoarthritis  1  61/1690 (3.61%)  89/1709 (5.21%) 
Pain in extremity  1  85/1690 (5.03%)  107/1709 (6.26%) 
Spinal pain  1  73/1690 (4.32%)  89/1709 (5.21%) 
Skin and subcutaneous tissue disorders     
Scar pain  1  86/1690 (5.09%)  78/1709 (4.56%) 
Vascular disorders     
Hot flush  1  234/1690 (13.85%)  270/1709 (15.80%) 
Hypertension  1  94/1690 (5.56%)  111/1709 (6.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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 Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
EMail: medinfo@amgen.com
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00556374    
Other Study ID Numbers: 20050209
ABCSG-18 ( Other Identifier: Austrian Breast and Colorectal Cancer Study Group )
2005-005275-15 ( EudraCT Number )
First Submitted: November 8, 2007
First Posted: November 12, 2007
Results First Submitted: October 6, 2015
Results First Posted: November 6, 2015
Last Update Posted: January 13, 2020