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Evaluation of New or Worsening Lens Opacifications in Men With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss

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: NCT00925600
Recruitment Status : Completed
First Posted : June 22, 2009
Results First Posted : May 30, 2017
Last Update Posted : May 30, 2017
Sponsor:
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
Conditions Cancer
Cataract
Low Bone Mineral Density
Osteopenia
Osteoporosis
Prostate Cancer
Interventions Biological: Denosumab
Biological: Placebo
Enrollment 769
Recruitment Details

This study was conducted at 125 centers in 18 countries: Australia, Bulgaria, Canada, the Czech Republic, France, Greece, Hungary, India, Latvia, Mexico, New Zealand, Poland, Russia, Slovakia, Slovenia, South Africa, Ukraine, and the United States.

The first participant enrolled on 30 November 2009 and the last participant enrolled on 04 May 2015.
Pre-assignment Details Participants were randomly assigned to receive denosumab or placebo in a 1:1 allocation ratio. Randomization was stratified on the basis of screening Lens Opacities Classification System (LOCS) III status (< 3.0 at all sites versus ≥ 3.0 at any site); age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description Participants randomized to receive placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants randomized to receive denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Period Title: Overall Study
Started 386 383
Received Treatment 383 [1] 382
Completed 354 355
Not Completed 32 28
Reason Not Completed
Withdrawal by Subject             16             14
Death             4             3
Lost to Follow-up             2             2
Disease Progression             1             3
Administrative Decision             1             1
Noncompliance             2             0
Ineligibility Determined             2             0
Protocol Deviation             0             1
Requirement for Alternative Therapy             0             1
Other             3             1
Adverse Event             1             2
[1]
Three participants received at least 1 dose of denosumab in error
Arm/Group Title Placebo Denosumab Total
Hide Arm/Group Description Participants randomized to receive placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants randomized to receive denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6. Total of all reporting groups
Overall Number of Baseline Participants 386 383 769
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 386 participants 383 participants 769 participants
71.0  (7.0) 71.1  (7.2) 71.0  (7.1)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 386 participants 383 participants 769 participants
18 - 64 years 73 66 139
65 - 74 years 189 194 383
75 - 84 years 119 116 235
≥ 85 years 5 7 12
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 386 participants 383 participants 769 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
386
 100.0%
383
 100.0%
769
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 386 participants 383 participants 769 participants
White 359 346 705
Black (or African American) 12 11 23
Hispanic/Latino 1 9 10
Other 7 8 15
Asian 7 7 14
Japanese 0 1 1
Native Hawaiian or Other Pacific Islander 0 1 1
Presence of Cataract(s)   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 386 participants 383 participants 769 participants
Yes 59 63 122
No 327 320 647
[1]
Measure Description: From baseline medical history
Presence of Diabetes   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 386 participants 383 participants 769 participants
Yes 70 61 131
No 316 322 638
[1]
Measure Description: From baseline medical history
Received Androgen-deprivation Therapy (ADT)  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 386 participants 383 participants 769 participants
Yes 350 353 703
No 36 30 66
Orchiectomy (Surgical Castration)  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 386 participants 383 participants 769 participants
Yes 58 51 109
No 328 332 660
Screening Lens Opacities Classification System (LOCS) III Status   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 386 participants 383 participants 769 participants
< 3.0 at all sites [P, C, and NO] 299 299 598
≥ 3.0 at any of these sites 87 84 171
[1]
Measure Description: The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity.
Participant-reported History of Cataract   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 386 participants 383 participants 769 participants
Yes 35 35 70
No 351 348 699
[1]
Measure Description: Participant-reported history of cataracts was a study stratification factor.
1.Primary Outcome
Title Percentage of Participants With Lens Opacification Event Development or Progression by Month 12
Hide Description The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site. Three participants randomized to placebo who received ≥ 1 dose of denosumab in error are analyzed in the denosumab group.
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.
Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Overall Number of Participants Analyzed 374 379
Measure Type: Number
Unit of Measure: percentage of participants
33.2 33.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments The primary endpoint was summarized with the point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (< 3.0 at all sites [P, C, and NO] vs. ≥ 3.0 at any of these sites), age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was demonstrated if the upper bound of the 97.5% one-sided confidence interval, or equivalently upper bound of two-sided 95% confidence interval was less than the pre-specified non-inferiority bound of 10%.
Statistical Test of Hypothesis P-Value 0.0026
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-6.3 to 7.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.4
Estimation Comments [Not Specified]
2.Other Pre-specified Outcome
Title Percentage of Participant With Lens Opacification Event Development or Progression by Month 12 Based on a Change of ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III Score
Hide Description The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III score from baseline.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site. Three participants randomized to placebo who eceived ≥ 1 dose of denosumab in error are analyzed in the denosumab group.
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.
Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Overall Number of Participants Analyzed 374 379
Measure Type: Number
Unit of Measure: percentage of participants
10.7 8.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments The point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval was constructed using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (< 3.0 at all sites [P, C, and NO] vs. ≥ 3.0 at any of these sites), age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-6.4 to 2.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.1
Estimation Comments [Not Specified]
3.Other Pre-specified Outcome
Title Percentage of Participants With Lens Opacification Event Development or Progression by Month 6
Hide Description The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 6 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Lens opacification analysis set includes randomized participants who received ≥1 dose of study drug, had an evaluable baseline and at least 1 evaluable post-baseline LOCS III assessment at the corresponding lens site at or before month 6. Three participants randomized to placebo who received denosumab in error are analyzed in the denosumab group.
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.
Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Overall Number of Participants Analyzed 374 379
Measure Type: Number
Unit of Measure: percentage of participants
19.3 19.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments The point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval was constructed using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (< 3.0 at all sites [P, C, and NO] vs. ≥ 3.0 at any of these sites), age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-5.9 to 5.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.9
Estimation Comments [Not Specified]
4.Other Pre-specified Outcome
Title Percentage of Participants With Confirmed Lens Opacification Event Development or Progression by Month 12
Hide Description

The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity.

Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline. A confirmed lens opacification event development or progression was defined as 2 directly subsequent events per protocol assessments at the same location (P, C, NO) using LOCS III as above.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description

Lens opacification analysis set with at least two post-baseline LOCS III measurements by month 12.

Three participants randomized to placebo who received at least 1 dose of denosumab in error are analyzed in the denosumab group.
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.
Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Overall Number of Participants Analyzed 361 367
Measure Type: Number
Unit of Measure: percentage of participants
18.3 16.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab
Comments The point estimate of absolute risk difference (difference in incidence rates, denosumab minus placebo) and the corresponding 95% confidence interval was constructed using the Mantel-Haenszel method adjusting for the stratification factors: baseline LOCS III status (< 3.0 at all sites [P, C, and NO] vs. ≥ 3.0 at any of these sites), age group (< 75, ≥ 75 years), and patient-reported history of cataract (yes/no).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-7.6 to 3.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.8
Estimation Comments [Not Specified]
5.Other Pre-specified Outcome
Title Percentage of Participants With a Decrease From Baseline in Best Corrected Visual Acuity (BCVA) of ≥ 10 Letters
Hide Description

The best corrected visual acuity (BCVA) is the best vision one can achieve with correction (such as eye glasses) as measured on an eye chart. BCVA was assessed by a trained ophthalmologist using the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at 4 meters. The modified University of Crete ETDRS chart was used in Ukraine, Greece, Russia and Bulgaria, which do not use the Roman alphabet. The 2000 series revised ETDRS chart was used to assess the change in all other countries.

The letter score was calculated based on the number of letters that were correctly identified; higher letter scores correspond to better visual acuity.
Time Frame Baseline and Months 3, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Lens opacification analysis set with evaluable assessments at both baseline and the time point of interest in the same eye (as indicated by "n"). Three participants randomized to placebo who received at least 1 dose of denosumab in error are analyzed in the denosumab group.
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.
Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Overall Number of Participants Analyzed 374 379
Measure Type: Number
Unit of Measure: percentage of participants
Month 3 (n = 372, 375) 5.4 6.1
Month 6 (n = 355, 357) 4.2 6.4
Month 9 (n = 350, 346) 4.6 6.6
Month 12 (n = 343, 342) 5.2 7.3
6.Other Pre-specified Outcome
Title Change From Baseline in Refraction Needed to Achieve BCVA
Hide Description Refraction error was measured using a phoropter. The change from baseline in spherical refraction error needed to achieve BCVA is reported.
Time Frame Baseline and months 3, 6, 9, and 12
Hide Outcome Measure Data
Hide Analysis Population Description

Lens opacification analysis set with evaluable assessments at both baseline and each time point in the same eye.

n=the number of evaluable eyes in the lens opacification analysis set at the corresponding time point; 3 participants randomized to placebo who received denosumab in error are analyzed in the denosumab group.
Arm/Group Title Placebo - Left Eye Placebo - Right Eye Denosumab Denosumab - Right Eye
Hide Arm/Group Description:
Participants received placebo subcutaneous injection on Day 1 and at Month 6.
Participants received placebo subcutaneous injection on Day 1 and at Month 6.
Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Overall Number of Participants Analyzed 374 374 379 379
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
 374 374 379 379
Mean (Standard Deviation)
Unit of Measure: diopters
Month 3 (n = 362, 358, 358, 359) 0.01  (0.60) 0.01  (0.49) 0.05  (0.73) 0.04  (0.51)
Month 6 (n = 347, 343, 341, 344) -0.01  (0.80) 0.06  (0.70) 0.06  (0.90) 0.04  (0.59)
Month 9 (n = 341, 339, 332, 332) 0.00  (0.84) 0.01  (0.73) 0.04  (0.75) 0.01  (0.62)
Month 12 (n = 336, 334, 328, 329) -0.03  (0.70) -0.04  (0.59) 0.03  (0.77) 0.00  (0.48)
7.Other Pre-specified Outcome
Title Number of Participants With Adverse Events
Hide Description

Adverse events (AEs) were assessed for severity by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) severity grading scale, version 3.0, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 =Life-threatening AE and Grade 5 = Death due to AE.

Treatment-related AEs (TRAEs) include only events for which the investigator indicated there was a reasonable possibility they may have been caused by the study drug.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who received at least one dose of study drug. Three participants randomized to the placebo group who received at least 1 dose of denosumab in error are analyzed in the denosumab group for safety.
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description:
Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.
Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
Overall Number of Participants Analyzed 380 385
Measure Type: Number
Unit of Measure: participants
Any adverse event 193 191
Serious adverse events 52 42
AE leading to discontinuation of study drug 5 7
AE leading to discontinuation from study 2 4
Fatal adverse events 4 3
AE grade 3, 4, or 5 53 46
Treatment-related adverse events 19 21
Serious treatment-related adverse events 1 2
TRAE leading to discontinuation of study drug 1 3
TRAE leading to discontinuation from study 0 1
Fatal treatment-related adverse events 0 0
TRAE grade 3, 4, or 5 2 2
Time Frame 12 months
Adverse Event Reporting Description

All enrolled participants who received at least one dose of study drug. Three participants randomized to the placebo group received at least 1 dose of denosumab in error, and are included in the denosumab group for safety.

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Placebo Denosumab
Hide Arm/Group Description Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6. Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.
All-Cause Mortality
Placebo Denosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Placebo Denosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   52/380 (13.68%)   42/385 (10.91%) 
Blood and lymphatic system disorders     
Anaemia megaloblastic † 1  1/380 (0.26%)  0/385 (0.00%) 
Cardiac disorders     
Angina pectoris † 1  0/380 (0.00%)  2/385 (0.52%) 
Atrial fibrillation † 1  1/380 (0.26%)  1/385 (0.26%) 
Cardiac failure † 1  0/380 (0.00%)  1/385 (0.26%) 
Cardiac failure congestive † 1  1/380 (0.26%)  0/385 (0.00%) 
Cardiac fibrillation † 1  1/380 (0.26%)  0/385 (0.00%) 
Cardio-respiratory arrest † 1  0/380 (0.00%)  1/385 (0.26%) 
Cardiogenic shock † 1  1/380 (0.26%)  0/385 (0.00%) 
Coronary artery disease † 1  2/380 (0.53%)  1/385 (0.26%) 
Coronary artery insufficiency † 1  1/380 (0.26%)  0/385 (0.00%) 
Coronary artery stenosis † 1  1/380 (0.26%)  0/385 (0.00%) 
Ischaemic cardiomyopathy † 1  0/380 (0.00%)  1/385 (0.26%) 
Myocardial infarction † 1  2/380 (0.53%)  1/385 (0.26%) 
Myocardial ischaemia † 1  1/380 (0.26%)  3/385 (0.78%) 
Tachycardia paroxysmal † 1  0/380 (0.00%)  1/385 (0.26%) 
Ventricular tachycardia † 1  0/380 (0.00%)  1/385 (0.26%) 
Ear and labyrinth disorders     
Tinnitus † 1  0/380 (0.00%)  1/385 (0.26%) 
Eye disorders     
Optic nerve disorder † 1  0/380 (0.00%)  1/385 (0.26%) 
Uveitis † 1  0/380 (0.00%)  1/385 (0.26%) 
Gastrointestinal disorders     
Abdominal pain † 1  1/380 (0.26%)  0/385 (0.00%) 
Colitis ulcerative † 1  0/380 (0.00%)  1/385 (0.26%) 
Diarrhoea † 1  2/380 (0.53%)  0/385 (0.00%) 
Gastrointestinal haemorrhage † 1  0/380 (0.00%)  1/385 (0.26%) 
Ileus † 1  1/380 (0.26%)  0/385 (0.00%) 
Inguinal hernia † 1  1/380 (0.26%)  1/385 (0.26%) 
Mechanical ileus † 1  1/380 (0.26%)  0/385 (0.00%) 
Rectal haemorrhage † 1  1/380 (0.26%)  1/385 (0.26%) 
Small intestinal stenosis † 1  0/380 (0.00%)  1/385 (0.26%) 
General disorders     
Asthenia † 1  1/380 (0.26%)  0/385 (0.00%) 
Cyst † 1  1/380 (0.26%)  0/385 (0.00%) 
Peripheral swelling † 1  1/380 (0.26%)  0/385 (0.00%) 
Pseudoangina † 1  1/380 (0.26%)  0/385 (0.00%) 
Pyrexia † 1  0/380 (0.00%)  1/385 (0.26%) 
Hepatobiliary disorders     
Bile duct stone † 1  0/380 (0.00%)  1/385 (0.26%) 
Cholecystitis acute † 1  1/380 (0.26%)  1/385 (0.26%) 
Cholelithiasis † 1  1/380 (0.26%)  0/385 (0.00%) 
Infections and infestations     
Appendicitis perforated † 1  1/380 (0.26%)  0/385 (0.00%) 
Arthritis bacterial † 1  1/380 (0.26%)  0/385 (0.00%) 
Atypical pneumonia † 1  1/380 (0.26%)  0/385 (0.00%) 
Diverticulitis † 1  2/380 (0.53%)  0/385 (0.00%) 
Herpes zoster † 1  1/380 (0.26%)  0/385 (0.00%) 
Kidney infection † 1  0/380 (0.00%)  1/385 (0.26%) 
Liver abscess † 1  0/380 (0.00%)  1/385 (0.26%) 
Pneumonia † 1  2/380 (0.53%)  0/385 (0.00%) 
Pyelonephritis acute † 1  1/380 (0.26%)  1/385 (0.26%) 
Injury, poisoning and procedural complications     
Cystitis radiation † 1  0/380 (0.00%)  1/385 (0.26%) 
Foot fracture † 1  1/380 (0.26%)  0/385 (0.00%) 
Fracture † 1  0/380 (0.00%)  1/385 (0.26%) 
Hip fracture † 1  1/380 (0.26%)  0/385 (0.00%) 
Lumbar vertebral fracture † 1  1/380 (0.26%)  1/385 (0.26%) 
Multiple injuries † 1  0/380 (0.00%)  1/385 (0.26%) 
Patella fracture † 1  1/380 (0.26%)  0/385 (0.00%) 
Radiation proctitis † 1  0/380 (0.00%)  1/385 (0.26%) 
Urethral stricture postoperative † 1  1/380 (0.26%)  1/385 (0.26%) 
Metabolism and nutrition disorders     
Dehydration † 1  0/380 (0.00%)  1/385 (0.26%) 
Diabetes mellitus inadequate control † 1  0/380 (0.00%)  1/385 (0.26%) 
Hyponatraemia † 1  1/380 (0.26%)  0/385 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  0/380 (0.00%)  1/385 (0.26%) 
Back pain † 1  1/380 (0.26%)  0/385 (0.00%) 
Connective tissue inflammation † 1  1/380 (0.26%)  0/385 (0.00%) 
Intervertebral disc compression † 1  0/380 (0.00%)  1/385 (0.26%) 
Osteoarthritis † 1  0/380 (0.00%)  2/385 (0.52%) 
Spinal osteoarthritis † 1  0/380 (0.00%)  1/385 (0.26%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer † 1  0/380 (0.00%)  1/385 (0.26%) 
Metastases to central nervous system † 1  1/380 (0.26%)  0/385 (0.00%) 
Plasma cell myeloma † 1  0/380 (0.00%)  1/385 (0.26%) 
Prostate cancer † 1  0/380 (0.00%)  1/385 (0.26%) 
Squamous cell carcinoma of skin † 1  1/380 (0.26%)  0/385 (0.00%) 
Nervous system disorders     
Aphasia † 1  1/380 (0.26%)  0/385 (0.00%) 
Cerebrovascular accident † 1  4/380 (1.05%)  1/385 (0.26%) 
Dementia † 1  1/380 (0.26%)  0/385 (0.00%) 
Dizziness † 1  2/380 (0.53%)  0/385 (0.00%) 
Encephalomalacia † 1  1/380 (0.26%)  0/385 (0.00%) 
Epilepsy † 1  1/380 (0.26%)  0/385 (0.00%) 
Haemorrhagic stroke † 1  1/380 (0.26%)  0/385 (0.00%) 
Normal pressure hydrocephalus † 1  0/380 (0.00%)  1/385 (0.26%) 
Syncope † 1  1/380 (0.26%)  1/385 (0.26%) 
Transient ischaemic attack † 1  1/380 (0.26%)  0/385 (0.00%) 
Product Issues     
Device dislocation † 1  0/380 (0.00%)  1/385 (0.26%) 
Device malfunction † 1  0/380 (0.00%)  1/385 (0.26%) 
Psychiatric disorders     
Depression † 1  1/380 (0.26%)  0/385 (0.00%) 
Renal and urinary disorders     
Acute kidney injury † 1  2/380 (0.53%)  0/385 (0.00%) 
Haematuria † 1  1/380 (0.26%)  1/385 (0.26%) 
Pelvi-ureteric obstruction † 1  1/380 (0.26%)  0/385 (0.00%) 
Stress urinary incontinence † 1  1/380 (0.26%)  0/385 (0.00%) 
Urethral stenosis † 1  1/380 (0.26%)  1/385 (0.26%) 
Urinary retention † 1  2/380 (0.53%)  0/385 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure † 1  1/380 (0.26%)  0/385 (0.00%) 
Chronic obstructive pulmonary disease † 1  1/380 (0.26%)  0/385 (0.00%) 
Chronic respiratory failure † 1  1/380 (0.26%)  0/385 (0.00%) 
Epistaxis † 1  0/380 (0.00%)  1/385 (0.26%) 
Pulmonary embolism † 1  2/380 (0.53%)  2/385 (0.52%) 
Pulmonary fibrosis † 1  1/380 (0.26%)  0/385 (0.00%) 
Skin and subcutaneous tissue disorders     
Diabetic foot † 1  1/380 (0.26%)  0/385 (0.00%) 
Rash generalised † 1  1/380 (0.26%)  0/385 (0.00%) 
Vascular disorders     
Deep vein thrombosis † 1  1/380 (0.26%)  0/385 (0.00%) 
Peripheral ischaemia † 1  1/380 (0.26%)  0/385 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Placebo Denosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   107/380 (28.16%)   121/385 (31.43%) 
Blood and lymphatic system disorders     
Anaemia † 1  4/380 (1.05%)  2/385 (0.52%) 
Cardiac disorders     
Atrial fibrillation † 1  3/380 (0.79%)  4/385 (1.04%) 
Ear and labyrinth disorders     
Vertigo † 1  0/380 (0.00%)  6/385 (1.56%) 
Eye disorders     
Vision blurred † 1  2/380 (0.53%)  5/385 (1.30%) 
Gastrointestinal disorders     
Constipation † 1  16/380 (4.21%)  8/385 (2.08%) 
Diarrhoea † 1  6/380 (1.58%)  2/385 (0.52%) 
General disorders     
Fatigue † 1  2/380 (0.53%)  6/385 (1.56%) 
Oedema peripheral † 1  1/380 (0.26%)  7/385 (1.82%) 
Infections and infestations     
Bronchitis † 1  4/380 (1.05%)  6/385 (1.56%) 
Nasopharyngitis † 1  7/380 (1.84%)  10/385 (2.60%) 
Sinusitis † 1  3/380 (0.79%)  4/385 (1.04%) 
Upper respiratory tract infection † 1  6/380 (1.58%)  5/385 (1.30%) 
Urinary tract infection † 1  5/380 (1.32%)  5/385 (1.30%) 
Injury, poisoning and procedural complications     
Chest injury † 1  4/380 (1.05%)  0/385 (0.00%) 
Investigations     
Prostatic specific antigen increased † 1  0/380 (0.00%)  4/385 (1.04%) 
Metabolism and nutrition disorders     
Diabetes mellitus † 1  5/380 (1.32%)  5/385 (1.30%) 
Type 2 diabetes mellitus † 1  4/380 (1.05%)  1/385 (0.26%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  10/380 (2.63%)  12/385 (3.12%) 
Back pain † 1  10/380 (2.63%)  11/385 (2.86%) 
Musculoskeletal pain † 1  5/380 (1.32%)  3/385 (0.78%) 
Myalgia † 1  2/380 (0.53%)  5/385 (1.30%) 
Osteoarthritis † 1  2/380 (0.53%)  7/385 (1.82%) 
Pain in extremity † 1  10/380 (2.63%)  6/385 (1.56%) 
Nervous system disorders     
Dizziness † 1  4/380 (1.05%)  6/385 (1.56%) 
Headache † 1  3/380 (0.79%)  6/385 (1.56%) 
Psychiatric disorders     
Insomnia † 1  3/380 (0.79%)  6/385 (1.56%) 
Renal and urinary disorders     
Dysuria † 1  4/380 (1.05%)  5/385 (1.30%) 
Haematuria † 1  4/380 (1.05%)  3/385 (0.78%) 
Pollakiuria † 1  6/380 (1.58%)  7/385 (1.82%) 
Urinary incontinence † 1  4/380 (1.05%)  1/385 (0.26%) 
Urinary retention † 1  4/380 (1.05%)  2/385 (0.52%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  6/380 (1.58%)  4/385 (1.04%) 
Dyspnoea † 1  3/380 (0.79%)  4/385 (1.04%) 
Vascular disorders     
Hot flush † 1  7/380 (1.84%)  7/385 (1.82%) 
Hypertension † 1  16/380 (4.21%)  8/385 (2.08%) 
Hypotension † 1  5/380 (1.32%)  1/385 (0.26%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
[Not Specified]
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
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00925600    
Other Study ID Numbers: 20080560
2009-012076-26 ( EudraCT Number )
First Submitted: June 18, 2009
First Posted: June 22, 2009
Results First Submitted: April 19, 2017
Results First Posted: May 30, 2017
Last Update Posted: May 30, 2017