Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 69 of 101 for:    Risedronate

Efficacy and Safety of Denosumab Compared With Risedronate in Individuals Taking Glucocorticoids (GIOP)

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: NCT01575873
Recruitment Status : Completed
First Posted : April 12, 2012
Results First Posted : July 27, 2018
Last Update Posted : July 27, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Steroid-induced Osteopor, Glucocorticoid-induced Ostepor
Interventions Drug: Denosumab
Drug: Placebo for risendronate
Drug: Risendronate
Drug: Placebo for denosumab
Enrollment 795
Recruitment Details

Participants were enrolled at 79 centers in Europe, North America, Latin America, and Korea from 28 March 2012 to 30 June 2015.

Participants who had been taking glucocorticoids for at least 3 months were classed as glucocorticoid continuing; those who were taking glucocorticoids for less than 3 months were classed as glucocorticoid initiating.

Pre-assignment Details Eligible patients were randomly assigned in a 1:1 ratio to receive 60 mg denosumab every 6 months or 5 mg oral risedronate daily for 24 months within each subpopulation. Randomization was stratified by sex within each subpopulation.
Arm/Group Title Risedronate: Glucocorticoid-initiating Denosumab: Glucocorticoid-initiating Risedronate: Glucocorticoid-continuing Denosumab: Glucocorticoid-continuing
Hide Arm/Group Description Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months. Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Period Title: Overall Study
Started 145 145 252 253
Received Study Drug 140 [1] 142 [2] 246 [1] 251 [2]
Completed 117 109 178 186
Not Completed 28 36 74 67
Reason Not Completed
Withdrawal by Subject             15             20             34             34
Adverse Event             7             7             9             12
Lost to Follow-up             1             3             13             5
Death             3             2             8             9
Noncompliance             1             2             4             3
Administrative decision             1             1             1             0
Protocol deviation             0             1             0             1
Requirement for Alternative Therapy             0             0             1             1
Other             0             0             4             2
[1]
Participants who received oral risedronate
[2]
Participants who received subcutaneous denosumab
Arm/Group Title Risedronate: Glucocorticoid-initiating Denosumab: Glucocorticoid-initiating Risedronate: Glucocorticoid-continuing Denosumab: Glucocorticoid-continuing Total
Hide Arm/Group Description Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months. Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months. Total of all reporting groups
Overall Number of Baseline Participants 145 145 252 253 795
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 145 participants 145 participants 252 participants 253 participants 795 participants
64.4  (10.0) 67.5  (10.1) 61.3  (11.1) 61.5  (11.6) 63.1  (11.1)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 145 participants 252 participants 253 participants 795 participants
< 50 years
5
   3.4%
2
   1.4%
26
  10.3%
33
  13.0%
66
   8.3%
50 - 64 years
75
  51.7%
55
  37.9%
130
  51.6%
114
  45.1%
374
  47.0%
65 - 74 years
38
  26.2%
50
  34.5%
62
  24.6%
73
  28.9%
223
  28.1%
≥ 75 years
27
  18.6%
38
  26.2%
34
  13.5%
33
  13.0%
132
  16.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 145 participants 252 participants 253 participants 795 participants
Female
93
  64.1%
93
  64.1%
185
  73.4%
185
  73.1%
556
  69.9%
Male
52
  35.9%
52
  35.9%
67
  26.6%
68
  26.9%
239
  30.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 145 participants 252 participants 253 participants 795 participants
Hispanic or Latino
18
  12.4%
20
  13.8%
54
  21.4%
43
  17.0%
135
  17.0%
Not Hispanic or Latino
127
  87.6%
125
  86.2%
198
  78.6%
210
  83.0%
660
  83.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 145 participants 252 participants 253 participants 795 participants
White
123
  84.8%
122
  84.1%
223
  88.5%
230
  90.9%
698
  87.8%
Other
11
   7.6%
12
   8.3%
11
   4.4%
13
   5.1%
47
   5.9%
Asian
9
   6.2%
9
   6.2%
12
   4.8%
6
   2.4%
36
   4.5%
Black or African American
2
   1.4%
2
   1.4%
4
   1.6%
4
   1.6%
12
   1.5%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
   0.4%
0
   0.0%
1
   0.1%
Multiple
0
   0.0%
0
   0.0%
1
   0.4%
0
   0.0%
1
   0.1%
Menopausal Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 93 participants 93 participants 185 participants 185 participants 556 participants
Premenopause
7
   7.5%
10
  10.8%
25
  13.5%
24
  13.0%
66
  11.9%
Postmenopause
83
  89.2%
82
  88.2%
157
  84.9%
159
  85.9%
481
  86.5%
Unknown
3
   3.2%
1
   1.1%
3
   1.6%
2
   1.1%
9
   1.6%
[1]
Measure Analysis Population Description: Females only
Lumbar Spine Bone Mineral Density (BMD) T-score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  T-score
Glucocorticoid-initiating Subpopulation Number Analyzed 143 participants 144 participants 0 participants 0 participants 287 participants
-1.06  (1.57) -0.92  (1.86) -0.99  (1.72)
Glucocorticoid-continuing Subpopulation Number Analyzed 0 participants 0 participants 252 participants 249 participants 501 participants
-1.96  (1.38) -1.92  (1.38) -1.94  (1.38)
[1]
Measure Description: The T-score is the bone mineral density (BMD) at the site when compared to that of a healthy thirty-year-old. Normal is a T-score of −1.0 or higher; Osteopenia is defined as between −1.0 and −2.5; Osteoporosis is defined as −2.5 or lower, meaning a bone density that is two and a half standard deviations below the mean of a thirty-year-old man/woman.
[2]
Measure Analysis Population Description: Participants with observed values
Total Hip BMD T-score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  T-score
Glucocorticoid-initiating Subpopulation Number Analyzed 142 participants 142 participants 0 participants 0 participants 284 participants
-0.98  (1.07) -1.14  (1.00) -1.06  (1.04)
Glucocorticoid-continuing Subpopulation Number Analyzed 0 participants 0 participants 250 participants 249 participants 499 participants
-1.56  (0.96) -1.66  (0.96) -1.61  (0.96)
[1]
Measure Description: The T-score is the bone mineral density (BMD) at the site when compared to that of a healthy thirty-year-old. Normal is a T-score of −1.0 or higher; Osteopenia is defined as between −1.0 and −2.5; Osteoporosis is defined as −2.5 or lower, meaning a bone density that is two and a half standard deviations below the mean of a thirty-year-old man/woman.
[2]
Measure Analysis Population Description: participants with observed vaues
1.Primary Outcome
Title Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 (Non-inferiority Analysis)
Hide Description Bone mineral density at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA).
Time Frame Baseline and month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and month 12 measurement for the lumbar spine BMD.
Arm/Group Title Risedronate: Glucocorticoid-initiating Denosumab: Glucocorticoid-initiating Risedronate: Glucocorticoid-continuing Denosumab: Glucocorticoid-continuing
Hide Arm/Group Description:
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Overall Number of Participants Analyzed 126 119 211 209
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
0.8
(0.2 to 1.5)
3.8
(3.1 to 4.5)
2.3
(1.7 to 2.9)
4.4
(3.8 to 5.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-initiating, Denosumab: Glucocorticoid-initiating
Comments

Analyses of the primary and secondary endpoints were performed independently within the glucocorticoid-continuing and glucocorticoid-initiating subpopulations. A fixed-sequence testing procedure was used to control the experiment-wise type 1 error rate at a two-sided 5% significance level within each subpopulation.

The glucocorticoid-initiating subpopulation was analyzed using an ANCOVA model adjusting for treatment, baseline BMD, sex, machine type, and baseline BMD-by-machine type interaction.

Type of Statistical Test Non-Inferiority
Comments Non-inferiority was shown if the lower bound of the two-sided 95% CI for the difference between the least-squares means (denosumab minus risedronate) was higher than the prespecified non-inferiority margin of –1.1 percentage points for the glucocorticoid-initiating subpopulation.
Statistical Test of Hypothesis P-Value < 0.001
Comments One-sided p-value based on the prespecified noninferiority margin for lumbar spine of -1.1%.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
2.0 to 3.9
Estimation Comments Least Squares (LS) Mean Difference = Denosumab - Risedronate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-continuing, Denosumab: Glucocorticoid-continuing
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-continuing subpopulation was analyzed using an ANCOVA model adjusted for treatment, baseline BMD, sex, machine type, baseline BMD-by-machine type interaction, and duration of prior glucocorticoid use (< 12 months vs ≥ 12 months).

Type of Statistical Test Non-Inferiority
Comments Non-inferiority was shown if the lower bound of the two-sided 95% CI for the difference between the least-squares means (denosumab minus risedronate) was higher than the prespecified non-inferiority margin of –0.7 percentage points for the glucocorticoid-continuing subpopulation.
Statistical Test of Hypothesis P-Value < 0.001
Comments One-sided p-value based on the prespecified noninferiority margins for lumbar spine of -0.7%.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
1.4 to 3.0
Estimation Comments LS Mean Difference = Denosumab - Risedronate
2.Secondary Outcome
Title Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 (Superiority Analysis)
Hide Description Bone mineral density at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA).
Time Frame Baseline and month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and month 12 measurement for the lumbar spine BMD.
Arm/Group Title Risedronate: Glucocorticoid-initiating Denosumab: Glucocorticoid-initiating Risedronate: Glucocorticoid-continuing Denosumab: Glucocorticoid-continuing
Hide Arm/Group Description:
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Overall Number of Participants Analyzed 126 119 211 209
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
0.8
(0.2 to 1.5)
3.8
(3.1 to 4.5)
2.3
(1.7 to 2.9)
4.4
(3.8 to 5.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-initiating, Denosumab: Glucocorticoid-initiating
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-initiating subpopulation was analyzed using an ANCOVA model adjusting for treatment, baseline BMD value, sex, machine type, and baseline BMD value-by-machine type interaction.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments 2-sided p-value corresponding to the 2-sided 95% confidence interval
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
2.0 to 3.9
Estimation Comments LS Mean Difference = Denosumab - Risedronate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-continuing, Denosumab: Glucocorticoid-continuing
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-continuing subpopulation was analyzed using an ANCOVA model adjusted for treatment, baseline BMD, sex, machine type, baseline BMD-by-machine type interaction, and duration of prior glucocorticoid use (< 12 months vs ≥ 12 months).

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments 2-sided p-value corresponding to the 2-sided 95% confidence interval
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
1.4 to 3.0
Estimation Comments LS Mean Difference = Denosumab - Risedronate
3.Secondary Outcome
Title Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12
Hide Description Bone mineral density at the total hip was measured by dual-energy x-ray absorptiometry (DXA).
Time Frame Baseline and month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and month 12 measurement for the total hip BMD.
Arm/Group Title Risedronate: Glucocorticoid-initiating Denosumab: Glucocorticoid-initiating Risedronate: Glucocorticoid-continuing Denosumab: Glucocorticoid-continuing
Hide Arm/Group Description:
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Overall Number of Participants Analyzed 128 119 215 217
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
0.2
(-0.2 to 0.7)
1.7
(1.2 to 2.2)
0.6
(0.2 to 1.0)
2.1
(1.7 to 2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-initiating, Denosumab: Glucocorticoid-initiating
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-initiating subpopulation was analyzed using an ANCOVA model adjusting for treatment, baseline BMD value, sex, machine type, and baseline BMD value-by-machine type interaction.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments 2-sided p-value corresponding to the 2-sided 95% confidence interval
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
0.8 to 2.1
Estimation Comments LS Mean Difference = Denosumab - Risedronate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-continuing, Denosumab: Glucocorticoid-continuing
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-continuing subpopulation was analyzed using an ANCOVA model adjusted for treatment, baseline BMD, sex, machine type, baseline BMD-by-machine type interaction, and duration of prior glucocorticoid use (< 12 months vs ≥ 12 months).

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments 2-sided p-value corresponding to the 2-sided 95% confidence interval
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
1.0 to 2.1
Estimation Comments LS Mean Difference = Denosumab - Risedronate
4.Secondary Outcome
Title Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 24
Hide Description Bone mineral density at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA).
Time Frame Baseline and month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and month 24 measurement for the lumbar spine BMD.
Arm/Group Title Risedronate: Glucocorticoid-initiating Denosumab: Glucocorticoid-initiating Risedronate: Glucocorticoid-continuing Denosumab: Glucocorticoid-continuing
Hide Arm/Group Description:
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Overall Number of Participants Analyzed 113 107 174 183
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
1.7
(0.8 to 2.7)
6.2
(5.3 to 7.2)
3.2
(2.3 to 4.1)
6.4
(5.5 to 7.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-initiating, Denosumab: Glucocorticoid-initiating
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-initiating subpopulation was analyzed using an ANCOVA model adjusting for treatment, baseline BMD value, sex, machine type, and baseline BMD value-by-machine type interaction.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments 2-sided p-value corresponding to the 2-sided 95% confidence interval
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.5
Confidence Interval (2-Sided) 95%
3.2 to 5.8
Estimation Comments LS Mean Difference = Denosumab - Risedronate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-continuing, Denosumab: Glucocorticoid-continuing
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-continuing subpopulation was analyzed using an ANCOVA model adjusted for treatment, baseline BMD, sex, machine type, baseline BMD-by-machine type interaction, and duration of prior glucocorticoid use (< 12 months vs ≥ 12 months).

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments 2-sided p-value corresponding to the 2-sided 95% confidence interval
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
2.0 to 4.3
Estimation Comments LS Mean Difference = Denosumab - Risedronate
5.Secondary Outcome
Title Percent Change From Baseline in Total Hip Bone Mineral Density at Month 24
Hide Description Bone mineral density at the total hip was measured by dual-energy x-ray absorptiometry (DXA).
Time Frame Baseline and month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a baseline and month 24 measurement for the total hip BMD.
Arm/Group Title Risedronate: Glucocorticoid-initiating Denosumab: Glucocorticoid-initiating Risedronate: Glucocorticoid-continuing Denosumab: Glucocorticoid-continuing
Hide Arm/Group Description:
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.
Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
Overall Number of Participants Analyzed 111 104 176 181
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
-0.0
(-0.6 to 0.6)
3.1
(2.4 to 3.7)
0.5
(-0.1 to 1.0)
2.9
(2.4 to 3.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-initiating, Denosumab: Glucocorticoid-initiating
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-initiating subpopulation was analyzed using an ANCOVA model adjusting for treatment, baseline BMD value, sex, machine type, and baseline BMD value-by-machine type interaction.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments 2-sided p-value corresponding to the 2-sided 95% confidence interval
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
2.2 to 3.9
Estimation Comments LS Mean Difference = Denosumab - Risedronate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Risedronate: Glucocorticoid-continuing, Denosumab: Glucocorticoid-continuing
Comments

Analyses of the primary and secondary endpoints were performed independently within each subpopulation using a fixed-sequence testing procedure to control the experiment-wise type 1 error rate at a two-sided 5% significance level.

The glucocorticoid-continuing subpopulation was analyzed using an ANCOVA model adjusted for treatment, baseline BMD, sex, machine type, baseline BMD-by-machine type interaction, and duration of prior glucocorticoid use (< 12 months vs ≥ 12 months).

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments 2-sided p-value corresponding to the 2-sided 95% confidence interval
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
1.7 to 3.2
Estimation Comments LS Mean Difference = Denosumab - Risedronate
Time Frame 24 months.
Adverse Event Reporting Description

One participant was randomized to risedronate but received denosumab in error; this participant was included in the denosumab group for safety analyses.

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

 
Arm/Group Title Risedronate Denosumab
Hide Arm/Group Description Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.
All-Cause Mortality
Risedronate Denosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   9/385 (2.34%)   13/394 (3.30%) 
Show Serious Adverse Events Hide Serious Adverse Events
Risedronate Denosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   98/385 (25.45%)   92/394 (23.35%) 
Blood and lymphatic system disorders     
Anaemia  1  2/385 (0.52%)  1/394 (0.25%) 
Cardiac disorders     
Acute myocardial infarction  1  2/385 (0.52%)  0/394 (0.00%) 
Aortic valve sclerosis  1  1/385 (0.26%)  0/394 (0.00%) 
Aortic valve stenosis  1  0/385 (0.00%)  1/394 (0.25%) 
Atrial fibrillation  1  1/385 (0.26%)  1/394 (0.25%) 
Atrial flutter  1  0/385 (0.00%)  1/394 (0.25%) 
Cardiac arrest  1  0/385 (0.00%)  1/394 (0.25%) 
Cardiac failure  1  0/385 (0.00%)  3/394 (0.76%) 
Cardiac failure acute  1  0/385 (0.00%)  2/394 (0.51%) 
Cardiac failure congestive  1  2/385 (0.52%)  2/394 (0.51%) 
Cardio-respiratory arrest  1  1/385 (0.26%)  0/394 (0.00%) 
Cardiopulmonary failure  1  0/385 (0.00%)  1/394 (0.25%) 
Coronary artery disease  1  0/385 (0.00%)  1/394 (0.25%) 
Mitral valve disease  1  1/385 (0.26%)  0/394 (0.00%) 
Myocardial infarction  1  1/385 (0.26%)  0/394 (0.00%) 
Myocardial ischaemia  1  0/385 (0.00%)  2/394 (0.51%) 
Ventricular tachycardia  1  0/385 (0.00%)  1/394 (0.25%) 
Congenital, familial and genetic disorders     
Congenital megaureter  1  0/385 (0.00%)  1/394 (0.25%) 
Ear and labyrinth disorders     
Vertigo  1  1/385 (0.26%)  0/394 (0.00%) 
Eye disorders     
Cataract  1  2/385 (0.52%)  1/394 (0.25%) 
Glaucoma  1  1/385 (0.26%)  0/394 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/385 (0.26%)  0/394 (0.00%) 
Abdominal pain upper  1  2/385 (0.52%)  0/394 (0.00%) 
Colitis ulcerative  1  2/385 (0.52%)  1/394 (0.25%) 
Constipation  1  0/385 (0.00%)  1/394 (0.25%) 
Diarrhoea  1  1/385 (0.26%)  0/394 (0.00%) 
Diverticulum  1  0/385 (0.00%)  1/394 (0.25%) 
Diverticulum intestinal  1  0/385 (0.00%)  1/394 (0.25%) 
Diverticulum intestinal haemorrhagic  1  1/385 (0.26%)  0/394 (0.00%) 
Dyspepsia  1  0/385 (0.00%)  2/394 (0.51%) 
Dysphagia  1  1/385 (0.26%)  0/394 (0.00%) 
Enterovesical fistula  1  1/385 (0.26%)  0/394 (0.00%) 
Erosive oesophagitis  1  0/385 (0.00%)  1/394 (0.25%) 
Gastric ulcer  1  0/385 (0.00%)  1/394 (0.25%) 
Gastritis  1  1/385 (0.26%)  0/394 (0.00%) 
Gastrooesophageal reflux disease  1  1/385 (0.26%)  0/394 (0.00%) 
Inguinal hernia  1  0/385 (0.00%)  1/394 (0.25%) 
Inguinal hernia strangulated  1  0/385 (0.00%)  1/394 (0.25%) 
Intestinal obstruction  1  0/385 (0.00%)  2/394 (0.51%) 
Large intestinal ulcer  1  0/385 (0.00%)  1/394 (0.25%) 
Large intestine perforation  1  1/385 (0.26%)  0/394 (0.00%) 
Lumbar hernia  1  0/385 (0.00%)  1/394 (0.25%) 
Oesophageal ulcer  1  1/385 (0.26%)  0/394 (0.00%) 
Pancreatitis  1  1/385 (0.26%)  0/394 (0.00%) 
Pancreatitis acute  1  1/385 (0.26%)  0/394 (0.00%) 
Peptic ulcer  1  1/385 (0.26%)  0/394 (0.00%) 
Small intestinal obstruction  1  0/385 (0.00%)  1/394 (0.25%) 
Subileus  1  2/385 (0.52%)  0/394 (0.00%) 
Umbilical hernia  1  0/385 (0.00%)  1/394 (0.25%) 
Upper gastrointestinal haemorrhage  1  1/385 (0.26%)  0/394 (0.00%) 
Vomiting  1  1/385 (0.26%)  1/394 (0.25%) 
General disorders     
Asthenia  1  0/385 (0.00%)  1/394 (0.25%) 
Death  1  1/385 (0.26%)  1/394 (0.25%) 
Non-cardiac chest pain  1  0/385 (0.00%)  1/394 (0.25%) 
Oedema peripheral  1  0/385 (0.00%)  1/394 (0.25%) 
Pyrexia  1  1/385 (0.26%)  0/394 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  0/385 (0.00%)  1/394 (0.25%) 
Biliary dyskinesia  1  1/385 (0.26%)  0/394 (0.00%) 
Cholecystitis acute  1  0/385 (0.00%)  1/394 (0.25%) 
Cholecystitis chronic  1  1/385 (0.26%)  0/394 (0.00%) 
Cholelithiasis  1  0/385 (0.00%)  2/394 (0.51%) 
Hepatic function abnormal  1  1/385 (0.26%)  0/394 (0.00%) 
Immune system disorders     
Eosinophilic granulomatosis with polyangiitis  1  1/385 (0.26%)  0/394 (0.00%) 
Food allergy  1  1/385 (0.26%)  0/394 (0.00%) 
Infections and infestations     
Abdominal abscess  1  1/385 (0.26%)  0/394 (0.00%) 
Abscess limb  1  1/385 (0.26%)  0/394 (0.00%) 
Anal abscess  1  1/385 (0.26%)  0/394 (0.00%) 
Arthritis infective  1  0/385 (0.00%)  1/394 (0.25%) 
Bronchitis  1  2/385 (0.52%)  0/394 (0.00%) 
Cellulitis  1  1/385 (0.26%)  0/394 (0.00%) 
Clostridium colitis  1  1/385 (0.26%)  0/394 (0.00%) 
Diverticulitis  1  1/385 (0.26%)  2/394 (0.51%) 
Erysipelas  1  1/385 (0.26%)  2/394 (0.51%) 
Escherichia sepsis  1  0/385 (0.00%)  1/394 (0.25%) 
Gastroenteritis  1  1/385 (0.26%)  1/394 (0.25%) 
Haemorrhagic fever  1  0/385 (0.00%)  1/394 (0.25%) 
Helicobacter gastritis  1  1/385 (0.26%)  0/394 (0.00%) 
Lower respiratory tract infection  1  0/385 (0.00%)  1/394 (0.25%) 
Lung abscess  1  0/385 (0.00%)  1/394 (0.25%) 
Lymph node tuberculosis  1  0/385 (0.00%)  1/394 (0.25%) 
Lymphangitis  1  1/385 (0.26%)  0/394 (0.00%) 
Necrotising fasciitis  1  1/385 (0.26%)  0/394 (0.00%) 
Peritonitis  1  1/385 (0.26%)  0/394 (0.00%) 
Peritonsillar abscess  1  1/385 (0.26%)  0/394 (0.00%) 
Pneumonia  1  8/385 (2.08%)  7/394 (1.78%) 
Pneumonia bacterial  1  0/385 (0.00%)  1/394 (0.25%) 
Post procedural infection  1  0/385 (0.00%)  1/394 (0.25%) 
Pyelonephritis acute  1  1/385 (0.26%)  1/394 (0.25%) 
Respiratory tract infection  1  1/385 (0.26%)  1/394 (0.25%) 
Sepsis  1  2/385 (0.52%)  0/394 (0.00%) 
Septic shock  1  1/385 (0.26%)  0/394 (0.00%) 
Serratia infection  1  0/385 (0.00%)  1/394 (0.25%) 
Sinusitis  1  1/385 (0.26%)  0/394 (0.00%) 
Upper respiratory tract infection  1  1/385 (0.26%)  1/394 (0.25%) 
Urinary tract infection  1  1/385 (0.26%)  1/394 (0.25%) 
Urinary tract infection bacterial  1  0/385 (0.00%)  1/394 (0.25%) 
Viral infection  1  1/385 (0.26%)  0/394 (0.00%) 
Wound infection bacterial  1  0/385 (0.00%)  1/394 (0.25%) 
Injury, poisoning and procedural complications     
Acetabulum fracture  1  0/385 (0.00%)  1/394 (0.25%) 
Chest injury  1  1/385 (0.26%)  0/394 (0.00%) 
Fall  1  1/385 (0.26%)  1/394 (0.25%) 
Femoral neck fracture  1  2/385 (0.52%)  0/394 (0.00%) 
Femur fracture  1  0/385 (0.00%)  3/394 (0.76%) 
Fibula fracture  1  1/385 (0.26%)  0/394 (0.00%) 
Humerus fracture  1  1/385 (0.26%)  1/394 (0.25%) 
Ligament rupture  1  0/385 (0.00%)  1/394 (0.25%) 
Limb injury  1  1/385 (0.26%)  0/394 (0.00%) 
Lumbar vertebral fracture  1  1/385 (0.26%)  1/394 (0.25%) 
Meniscus injury  1  0/385 (0.00%)  1/394 (0.25%) 
Multiple injuries  1  0/385 (0.00%)  1/394 (0.25%) 
Patella fracture  1  1/385 (0.26%)  0/394 (0.00%) 
Pneumothorax traumatic  1  1/385 (0.26%)  0/394 (0.00%) 
Pubis fracture  1  1/385 (0.26%)  0/394 (0.00%) 
Radius fracture  1  0/385 (0.00%)  1/394 (0.25%) 
Rib fracture  1  0/385 (0.00%)  2/394 (0.51%) 
Subarachnoid haemorrhage  1  0/385 (0.00%)  1/394 (0.25%) 
Thoracic vertebral fracture  1  2/385 (0.52%)  0/394 (0.00%) 
Tibia fracture  1  1/385 (0.26%)  0/394 (0.00%) 
Toxicity to various agents  1  0/385 (0.00%)  1/394 (0.25%) 
Traumatic haemothorax  1  0/385 (0.00%)  1/394 (0.25%) 
Investigations     
Blood creatinine increased  1  0/385 (0.00%)  1/394 (0.25%) 
Blood pressure increased  1  1/385 (0.26%)  0/394 (0.00%) 
White blood cell count increased  1  1/385 (0.26%)  0/394 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/385 (0.00%)  2/394 (0.51%) 
Hypercalcaemia  1  0/385 (0.00%)  1/394 (0.25%) 
Hyperglycaemia  1  1/385 (0.26%)  0/394 (0.00%) 
Ketosis  1  1/385 (0.26%)  0/394 (0.00%) 
Periarthritis calcarea  1  1/385 (0.26%)  0/394 (0.00%) 
Musculoskeletal and connective tissue disorders     
Ankylosing spondylitis  1  0/385 (0.00%)  1/394 (0.25%) 
Arthralgia  1  1/385 (0.26%)  0/394 (0.00%) 
Back pain  1  3/385 (0.78%)  1/394 (0.25%) 
Bursitis  1  0/385 (0.00%)  1/394 (0.25%) 
Exposed bone in jaw  1  0/385 (0.00%)  1/394 (0.25%) 
Intervertebral disc degeneration  1  0/385 (0.00%)  2/394 (0.51%) 
Intervertebral disc protrusion  1  1/385 (0.26%)  0/394 (0.00%) 
Lumbar spinal stenosis  1  1/385 (0.26%)  1/394 (0.25%) 
Mixed connective tissue disease  1  1/385 (0.26%)  0/394 (0.00%) 
Muscle haemorrhage  1  0/385 (0.00%)  1/394 (0.25%) 
Musculoskeletal pain  1  1/385 (0.26%)  0/394 (0.00%) 
Neck pain  1  0/385 (0.00%)  1/394 (0.25%) 
Osteoarthritis  1  5/385 (1.30%)  2/394 (0.51%) 
Osteonecrosis  1  2/385 (0.52%)  1/394 (0.25%) 
Pain in extremity  1  1/385 (0.26%)  0/394 (0.00%) 
Polymyalgia rheumatica  1  1/385 (0.26%)  2/394 (0.51%) 
Rheumatoid arthritis  1  2/385 (0.52%)  2/394 (0.51%) 
Sjogren's syndrome  1  1/385 (0.26%)  0/394 (0.00%) 
Synovitis  1  0/385 (0.00%)  1/394 (0.25%) 
Vertebral foraminal stenosis  1  0/385 (0.00%)  1/394 (0.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  0/385 (0.00%)  1/394 (0.25%) 
Breast cancer  1  1/385 (0.26%)  0/394 (0.00%) 
Colon cancer  1  1/385 (0.26%)  0/394 (0.00%) 
Gastrointestinal stromal tumour  1  0/385 (0.00%)  1/394 (0.25%) 
Invasive ductal breast carcinoma  1  0/385 (0.00%)  1/394 (0.25%) 
Lung neoplasm  1  1/385 (0.26%)  0/394 (0.00%) 
Metastases to liver  1  0/385 (0.00%)  1/394 (0.25%) 
Metastases to lung  1  0/385 (0.00%)  1/394 (0.25%) 
Metastatic neoplasm  1  0/385 (0.00%)  1/394 (0.25%) 
Neoplasm  1  0/385 (0.00%)  1/394 (0.25%) 
Prostate cancer  1  1/385 (0.26%)  1/394 (0.25%) 
Prostatic adenoma  1  0/385 (0.00%)  1/394 (0.25%) 
Rectal cancer metastatic  1  0/385 (0.00%)  1/394 (0.25%) 
Squamous cell carcinoma of skin  1  2/385 (0.52%)  0/394 (0.00%) 
Uterine leiomyoma  1  0/385 (0.00%)  2/394 (0.51%) 
Nervous system disorders     
Ataxia  1  1/385 (0.26%)  0/394 (0.00%) 
Cerebral ischaemia  1  0/385 (0.00%)  1/394 (0.25%) 
Cerebrovascular accident  1  1/385 (0.26%)  3/394 (0.76%) 
Cervicobrachial syndrome  1  1/385 (0.26%)  0/394 (0.00%) 
Headache  1  0/385 (0.00%)  1/394 (0.25%) 
Hemiparesis  1  1/385 (0.26%)  0/394 (0.00%) 
Hydrocephalus  1  1/385 (0.26%)  0/394 (0.00%) 
Multiple sclerosis  1  1/385 (0.26%)  0/394 (0.00%) 
Paresis  1  0/385 (0.00%)  1/394 (0.25%) 
Parkinson's disease  1  0/385 (0.00%)  1/394 (0.25%) 
Presyncope  1  1/385 (0.26%)  0/394 (0.00%) 
Sciatica  1  1/385 (0.26%)  2/394 (0.51%) 
Seizure  1  0/385 (0.00%)  1/394 (0.25%) 
Transient ischaemic attack  1  1/385 (0.26%)  3/394 (0.76%) 
Psychiatric disorders     
Anxiety  1  1/385 (0.26%)  0/394 (0.00%) 
Behaviour disorder due to a general medical condition  1  0/385 (0.00%)  1/394 (0.25%) 
Confusional state  1  1/385 (0.26%)  0/394 (0.00%) 
Delirium  1  1/385 (0.26%)  0/394 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/385 (0.26%)  2/394 (0.51%) 
Lupus nephritis  1  1/385 (0.26%)  1/394 (0.25%) 
Nephrolithiasis  1  1/385 (0.26%)  0/394 (0.00%) 
Renal failure  1  2/385 (0.52%)  1/394 (0.25%) 
Urinary retention  1  0/385 (0.00%)  1/394 (0.25%) 
Reproductive system and breast disorders     
Cervix haematoma uterine  1  0/385 (0.00%)  1/394 (0.25%) 
Cystocele  1  1/385 (0.26%)  0/394 (0.00%) 
Menorrhagia  1  0/385 (0.00%)  1/394 (0.25%) 
Ovarian cyst  1  0/385 (0.00%)  1/394 (0.25%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  2/385 (0.52%)  0/394 (0.00%) 
Alveolitis allergic  1  0/385 (0.00%)  1/394 (0.25%) 
Asthma  1  2/385 (0.52%)  0/394 (0.00%) 
Bronchopneumopathy  1  0/385 (0.00%)  1/394 (0.25%) 
Chronic obstructive pulmonary disease  1  3/385 (0.78%)  1/394 (0.25%) 
Chronic respiratory failure  1  1/385 (0.26%)  0/394 (0.00%) 
Dyspnoea  1  1/385 (0.26%)  0/394 (0.00%) 
Interstitial lung disease  1  0/385 (0.00%)  1/394 (0.25%) 
Organising pneumonia  1  0/385 (0.00%)  1/394 (0.25%) 
Pneumothorax  1  0/385 (0.00%)  1/394 (0.25%) 
Pulmonary embolism  1  5/385 (1.30%)  0/394 (0.00%) 
Pulmonary fibrosis  1  0/385 (0.00%)  1/394 (0.25%) 
Vocal cord polyp  1  1/385 (0.26%)  0/394 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatomyositis  1  1/385 (0.26%)  0/394 (0.00%) 
Pruritus generalised  1  1/385 (0.26%)  0/394 (0.00%) 
Surgical and medical procedures     
Cataract operation  1  1/385 (0.26%)  0/394 (0.00%) 
Colectomy  1  1/385 (0.26%)  0/394 (0.00%) 
Ileostomy  1  1/385 (0.26%)  0/394 (0.00%) 
Knee arthroplasty  1  2/385 (0.52%)  1/394 (0.25%) 
Lung neoplasm surgery  1  1/385 (0.26%)  0/394 (0.00%) 
Lymphadenectomy  1  0/385 (0.00%)  1/394 (0.25%) 
Sigmoidectomy  1  0/385 (0.00%)  1/394 (0.25%) 
Spinal decompression  1  0/385 (0.00%)  1/394 (0.25%) 
Vascular disorders     
Aortic stenosis  1  1/385 (0.26%)  0/394 (0.00%) 
Capillary leak syndrome  1  0/385 (0.00%)  1/394 (0.25%) 
Deep vein thrombosis  1  2/385 (0.52%)  0/394 (0.00%) 
Haemodynamic instability  1  1/385 (0.26%)  0/394 (0.00%) 
Temporal arteritis  1  0/385 (0.00%)  1/394 (0.25%) 
Thrombosis  1  1/385 (0.26%)  0/394 (0.00%) 
Vasculitis  1  1/385 (0.26%)  2/394 (0.51%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Risedronate Denosumab
Affected / at Risk (%) Affected / at Risk (%)
Total   76/385 (19.74%)   77/394 (19.54%) 
Infections and infestations     
Viral upper respiratory tract infection  1  19/385 (4.94%)  20/394 (5.08%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  33/385 (8.57%)  23/394 (5.84%) 
Back pain  1  21/385 (5.45%)  24/394 (6.09%) 
Vascular disorders     
Hypertension  1  15/385 (3.90%)  21/394 (5.33%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01575873     History of Changes
Other Study ID Numbers: 20101217
2010-024393-19 ( EudraCT Number )
First Submitted: April 10, 2012
First Posted: April 12, 2012
Results First Submitted: June 13, 2018
Results First Posted: July 27, 2018
Last Update Posted: July 27, 2018