Trial Outcomes & Findings for Denosumab China Phase III Study (NCT NCT02014467)
NCT ID: NCT02014467
Last Updated: 2016-10-31
Results Overview
Bone mineral density (BMD) is the amount of bone mineral in bone tissue. BMD scan was done using dual energy x-ray absorptiometry (DXA). It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calcuated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. The analysis was performed by Analysis of Covariance (ANCOVA) model adjusted for treatment, region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as Baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the Last Observation Carried Forward (LOCF), provided the assessment was taken on or after at least one month on-therapy.
COMPLETED
PHASE3
486 participants
Baseline and Month 12
2016-10-31
Participant Flow
The study design consists of two phases: Screening Phase and 12-month Double-blind Treatment Phase. The Screening Phase was to last up to a maximum of 2.5 months, which was followed by a 12-month Double-blind Treatment Phase. The total participation time in the study was approximately 14.5 months.
A total of 909 participants were screened, of whom 485 were randomized in a 3: 1 ratio to receive one of the two study treatments. A total of 484 participants received at least single dose of investigational product (IP).
Participant milestones
| Measure |
Denosumab 60 mg
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase.Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Overall Study
STARTED
|
365
|
119
|
|
Overall Study
COMPLETED
|
340
|
112
|
|
Overall Study
NOT COMPLETED
|
25
|
7
|
Reasons for withdrawal
| Measure |
Denosumab 60 mg
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase.Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
0
|
|
Overall Study
Protocol Violation
|
3
|
0
|
|
Overall Study
Physician Decision
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
16
|
4
|
Baseline Characteristics
Denosumab China Phase III Study
Baseline characteristics by cohort
| Measure |
Denosumab 60 mg
n=365 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=119 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
Total
n=484 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
68.9 Years
STANDARD_DEVIATION 6.10 • n=5 Participants
|
69.6 Years
STANDARD_DEVIATION 5.75 • n=7 Participants
|
69.0 Years
STANDARD_DEVIATION 6.02 • n=5 Participants
|
|
Sex: Female, Male
Female
|
365 Participants
n=5 Participants
|
119 Participants
n=7 Participants
|
484 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian Heritage
|
365 Participants
n=5 Participants
|
119 Participants
n=7 Participants
|
484 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Month 12Population: Intent-to-Treat (ITT) Population: all safety Population participants (consisting of all participants who received at least one dose of study medication) who had a Baseline and at least one valid post-Baseline efficacy measure. Participants with values at Baseline and Month 12 were included in the analysis.
Bone mineral density (BMD) is the amount of bone mineral in bone tissue. BMD scan was done using dual energy x-ray absorptiometry (DXA). It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calcuated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. The analysis was performed by Analysis of Covariance (ANCOVA) model adjusted for treatment, region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as Baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the Last Observation Carried Forward (LOCF), provided the assessment was taken on or after at least one month on-therapy.
Outcome measures
| Measure |
Denosumab 60 mg
n=350 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=116 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine at Month 12
|
5.22 Percentage change
Standard Error 0.274
|
0.79 Percentage change
Standard Error 0.391
|
SECONDARY outcome
Timeframe: Baseline and Month 6Population: ITT Population. Participants with values at Baseline and Month 6 were included in the analysis.
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Outcome measures
| Measure |
Denosumab 60 mg
n=350 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=116 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change From Baseline in BMD at the Lumbar Spine at Month 6
|
3.77 Percentage change
Standard Error 0.273
|
0.57 Percentage change
Standard Error 0.390
|
SECONDARY outcome
Timeframe: Baseline and Month 6Population: ITT Population. Participants with values at Baseline and Month 6 were included in the analysis.
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Outcome measures
| Measure |
Denosumab 60 mg
n=347 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=115 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change From Baseline in BMD at the Total Hip at Month 6
|
2.36 Percentage change
Standard Error 0.193
|
0.11 Percentage change
Standard Error 0.279
|
SECONDARY outcome
Timeframe: Baseline and Month 6Population: ITT Population. Participants with values at Baseline and Month 6 were included in the analysis.
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Outcome measures
| Measure |
Denosumab 60 mg
n=347 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=115 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change From Baseline in BMD at the Femoral Neck at Month 6
|
1.91 Percentage change
Standard Error 0.219
|
0.32 Percentage change
Standard Error 0.315
|
SECONDARY outcome
Timeframe: Baseline and Month 6Population: ITT Population. Participants with values at Baseline and Month 6 were included in the analysis.
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Outcome measures
| Measure |
Denosumab 60 mg
n=347 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=115 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change From Baseline in BMD at the Trochanter at Month 6
|
2.76 Percentage change
Standard Error 0.344
|
-0.59 Percentage change
Standard Error 0.498
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: ITT Population. Participants with values at Baseline and Month 12 were included in the analysis.
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Outcome measures
| Measure |
Denosumab 60 mg
n=348 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=115 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change From Baseline in BMD at the Total Hip at Month 12
|
3.03 Percentage change
Standard Error 0.202
|
-0.28 Percentage change
Standard Error 0.293
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: ITT Population. Participants with values at Baseline and Month 12 were included in the analysis.
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Outcome measures
| Measure |
Denosumab 60 mg
n=348 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=115 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change From Baseline in BMD at the Femoral Neck at Month 12
|
2.77 Percentage change
Standard Error 0.233
|
0.16 Percentage change
Standard Error 0.337
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: ITT Population. Participants with values at Baseline and Month 12 were included in the analysis.
BMD is the amount of bone mineral in bone tissue. BMD scan was done using DXA. It is used to identify osteoporosis, determine risk for fractures, and measure response to osteoporosis treatment. The percentage change from Baseline for BMD was calculated as the value at the indicated time point minus the Baseline value multiplied by 100 and divided by the Baseline value. ANCOVA model adjusted for treatment, center/region and Baseline BMD for the skeletal site under consideration as a continuous covariate for assessment. Region and treatment by region interaction was included in the model. Screening visit was considered as baseline for BMD. For participants who withdrew early, the missing BMD assessments was estimated by the LOCF, provided the assessment was taken on or after at least one month on-therapy.
Outcome measures
| Measure |
Denosumab 60 mg
n=348 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=115 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change From Baseline in BMD at the Trochanter at Month 12
|
3.88 Percentage change
Standard Error 0.356
|
-0.83 Percentage change
Standard Error 0.517
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: ITT Population. Only those participants with values at Baseline and Month 6 and Month 12 are included in the analysis (represented by n=X, X in the category titles).
s-CTX is biomarker of bone resorption and formation. s-CTX was assessed during Screening, Month 6 and Month 12 in the Double-blind Treatment Phase. The value during Screening was considered as the Baseline value. Percent change from Baseline was assessed as the value at the indicated visit minus the Baseline value divided by the Baseline value x 100. A two-sided Wilcoxon rank sum test was used to compare percent change in s-CTX. Between group inferences is presented by p-values, Hodges-Lehmann estimates along with 95% confidence intervals.
Outcome measures
| Measure |
Denosumab 60 mg
n=354 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) From Baseline to Month 6 and Month 12
s-CTX, Month 6, n=353, 117
|
-79.20 Percentage change
Interval -86.8 to -66.45
|
-19.35 Percentage change
Interval -35.97 to -2.74
|
|
Percent Change in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) From Baseline to Month 6 and Month 12
s-CTX, Month 12, n=335, 108
|
-64.51 Percentage change
Interval -77.29 to -38.52
|
-5.94 Percentage change
Interval -29.52 to 16.67
|
SECONDARY outcome
Timeframe: Baseline, Month 6, Month 12Population: ITT Population: Only those participants with values at Baseline and Month 6 and Month 12 are included in the analysis (represented by n=X, X in the category titles).
s-PINP is biomarker of bone resorption and formation. s-PINP was assessed during Screening, Month 6 and Month 12 in the Double-blind Treatment Phase. The value during Screening was considered as the Baseline value. Percent change from Baseline was assessed as the value at the indicated visit minus the Baseline value divided by the Baseline value x 100. A two-sided Wilcoxon rank sum test was used to compare percent change in serum CTX. Between group inferences is presented by p-values, Hodges-Lehmann estimates along with 95% confidence intervals.
Outcome measures
| Measure |
Denosumab 60 mg
n=352 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Percent Change in Serum Procollagen Type I N Propeptideserum (s-PINP) From Baseline to Month 6 and Month 12
s-PINP, Month 6, n=352, 117
|
-73.12 Percentage change
Interval -81.03 to -62.81
|
-12.37 Percentage change
Interval -29.58 to 4.37
|
|
Percent Change in Serum Procollagen Type I N Propeptideserum (s-PINP) From Baseline to Month 6 and Month 12
s-PINP, Month 12, n=335, 108
|
-66.14 Percentage change
Interval -76.04 to -50.75
|
-14.83 Percentage change
Interval -27.84 to 11.26
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 3, Month 6 and Month 12Population: Safety Population: all participants who received at least one dose of study medication. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Randomization (Visit 3). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Change from Baseline in SBP and DBP was assessed at Baseline, Month 1, Month 3, Month 6, and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
SBP, Month 3, n = 362, 117
|
-3.4 Millimeters of mercury (mmHg)
Standard Deviation 12.62
|
-0.5 Millimeters of mercury (mmHg)
Standard Deviation 12.16
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
SBP, Month 12, n = 342, 110
|
-0.5 Millimeters of mercury (mmHg)
Standard Deviation 11.83
|
-0.1 Millimeters of mercury (mmHg)
Standard Deviation 11.69
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
DBP, Month 1, n = 365, 117
|
0.0 Millimeters of mercury (mmHg)
Standard Deviation 6.95
|
0.6 Millimeters of mercury (mmHg)
Standard Deviation 7.58
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
DBP, Month 3, n = 362, 117
|
-1.5 Millimeters of mercury (mmHg)
Standard Deviation 7.70
|
0.2 Millimeters of mercury (mmHg)
Standard Deviation 6.50
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
DBP, Month 6, n = 350, 114
|
-0.3 Millimeters of mercury (mmHg)
Standard Deviation 7.67
|
1.1 Millimeters of mercury (mmHg)
Standard Deviation 8.34
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
DBP, Month 12, n = 342, 110
|
0.2 Millimeters of mercury (mmHg)
Standard Deviation 7.63
|
1.2 Millimeters of mercury (mmHg)
Standard Deviation 7.75
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
SBP, Month 6, n = 350, 114
|
0.1 Millimeters of mercury (mmHg)
Standard Deviation 12.76
|
1.5 Millimeters of mercury (mmHg)
Standard Deviation 13.25
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 1, Month 3, Month 6, and Month 12
SBP, Month 1, n = 365, 117
|
-1.8 Millimeters of mercury (mmHg)
Standard Deviation 11.01
|
-1.3 Millimeters of mercury (mmHg)
Standard Deviation 11.89
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 3, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Randomization (Visit 3). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Change from Baseline in heart rate was assessed at Baseline, Month 1, Month 3, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Heart Rate at Month 1, Month 3, Month 6, and Month 12
Heart Rate, Month 3, n = 362, 117
|
1.2 Beats per minute
Standard Deviation 10.28
|
0.2 Beats per minute
Standard Deviation 9.08
|
|
Change From Baseline in Heart Rate at Month 1, Month 3, Month 6, and Month 12
Heart Rate, Month 6, n = 350, 114
|
-0.4 Beats per minute
Standard Deviation 8.23
|
-1.3 Beats per minute
Standard Deviation 9.01
|
|
Change From Baseline in Heart Rate at Month 1, Month 3, Month 6, and Month 12
Heart Rate, Month 12, n = 342, 110
|
-0.9 Beats per minute
Standard Deviation 7.55
|
0.1 Beats per minute
Standard Deviation 10.48
|
|
Change From Baseline in Heart Rate at Month 1, Month 3, Month 6, and Month 12
Heart Rate, Month 1, n = 365, 117
|
-0.8 Beats per minute
Standard Deviation 6.88
|
-2.1 Beats per minute
Standard Deviation 7.51
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 6, and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline values were obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Alanine amino transferase, alkaline phosphatase, aspartate amino transferase, and gamma glutamyl transferase were assessed at Baseline, Month 1, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Alkaline Phosphatase, Month 1, n = 365, 117
|
-3.3 International unit per liter (IU/L)
Standard Deviation 11.00
|
-3.2 International unit per liter (IU/L)
Standard Deviation 10.03
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Aspartate Amino Transferase,Month 12, n = 340, 109
|
0.1 International unit per liter (IU/L)
Standard Deviation 7.41
|
-0.8 International unit per liter (IU/L)
Standard Deviation 5.94
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Alanine Amino Transferase, Month 1, n = 365, 117
|
0.2 International unit per liter (IU/L)
Standard Deviation 6.27
|
-0.1 International unit per liter (IU/L)
Standard Deviation 5.91
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Alanine Amino Transferase, Month 6, n = 350, 114
|
1.9 International unit per liter (IU/L)
Standard Deviation 9.00
|
0.7 International unit per liter (IU/L)
Standard Deviation 7.19
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Alanine Amino Transferase, Month 12, n = 340, 109
|
1.5 International unit per liter (IU/L)
Standard Deviation 12.49
|
0.2 International unit per liter (IU/L)
Standard Deviation 8.45
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Alkaline Phosphatase, Month 6, n = 350, 114
|
-21.0 International unit per liter (IU/L)
Standard Deviation 17.20
|
-1.2 International unit per liter (IU/L)
Standard Deviation 11.43
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Alkaline Phosphatase, Month 12, n = 340, 109
|
-23.4 International unit per liter (IU/L)
Standard Deviation 17.36
|
-5.3 International unit per liter (IU/L)
Standard Deviation 11.06
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Aspartate Amino Transferase, Month 1, n = 365, 117
|
-0.1 International unit per liter (IU/L)
Standard Deviation 4.34
|
-0.4 International unit per liter (IU/L)
Standard Deviation 4.41
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Aspartate Amino Transferase, Month 6, n = 350, 114
|
1.2 International unit per liter (IU/L)
Standard Deviation 7.84
|
0.2 International unit per liter (IU/L)
Standard Deviation 5.28
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Gamma Glutamyl Transferase, Month 1, n = 365, 117
|
0.2 International unit per liter (IU/L)
Standard Deviation 11.52
|
-0.6 International unit per liter (IU/L)
Standard Deviation 5.82
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Gamma Glutamyl Transferase, Month 6, n = 350, 114
|
0.1 International unit per liter (IU/L)
Standard Deviation 11.22
|
-0.1 International unit per liter (IU/L)
Standard Deviation 6.44
|
|
Change From Baseline in Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Month 1, Month 6 and Month 12
Gamma Glutamyl Transferase, Month 12, n = 340, 109
|
-0.9 International unit per liter (IU/L)
Standard Deviation 9.96
|
0.3 International unit per liter (IU/L)
Standard Deviation 10.09
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline values was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Creatine kinase and lactate dehydrogenase were assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Creatine Kinase, Lactate Dehydrogenase at Month 6 and Month 12.
Creatine Kinase, Month 6, n = 350, 114
|
-3.7 International unit per liter (IU/L)
Standard Deviation 43.41
|
-3.7 International unit per liter (IU/L)
Standard Deviation 31.64
|
|
Change From Baseline in Creatine Kinase, Lactate Dehydrogenase at Month 6 and Month 12.
Creatine Kinase, Month 12, n = 340, 109
|
-2.6 International unit per liter (IU/L)
Standard Deviation 53.83
|
-0.3 International unit per liter (IU/L)
Standard Deviation 38.58
|
|
Change From Baseline in Creatine Kinase, Lactate Dehydrogenase at Month 6 and Month 12.
Lactate Dehydrogenase, Month 6, n = 350, 114
|
-3.4 International unit per liter (IU/L)
Standard Deviation 19.62
|
-5.6 International unit per liter (IU/L)
Standard Deviation 19.60
|
|
Change From Baseline in Creatine Kinase, Lactate Dehydrogenase at Month 6 and Month 12.
Lactate Dehydrogenase, Month 12, n = 340, 109
|
-2.2 International unit per liter (IU/L)
Standard Deviation 18.50
|
-4.0 International unit per liter (IU/L)
Standard Deviation 23.16
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 6 and Month 12.Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Albumin was assessed at Baseline, Month 1, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Albumin at Month 1, Month 6 and Month 12.
Albumin, Month 1, n = 365, 117
|
-0.6 Gram per liter (G/L)
Standard Deviation 1.93
|
-0.7 Gram per liter (G/L)
Standard Deviation 1.75
|
|
Change From Baseline in Albumin at Month 1, Month 6 and Month 12.
Albumin, Month 6, n = 350, 114
|
0.7 Gram per liter (G/L)
Standard Deviation 1.96
|
0.5 Gram per liter (G/L)
Standard Deviation 2.09
|
|
Change From Baseline in Albumin at Month 1, Month 6 and Month 12.
Albumin, Month 12, n = 340, 109
|
0.2 Gram per liter (G/L)
Standard Deviation 1.82
|
0.1 Gram per liter (G/L)
Standard Deviation 2.11
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at indicated visit minus the Baseline value. Blood samples were collected for measurement. Globulin was assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Globulin at Month 6 and Month 12.
Globulin, Month 6, n = 350, 114
|
-0.3 Grams per liter (G/L)
Standard Deviation 2.29
|
-0.2 Grams per liter (G/L)
Standard Deviation 2.35
|
|
Change From Baseline in Globulin at Month 6 and Month 12.
Globulin, Month 12, n = 340, 109
|
-0.5 Grams per liter (G/L)
Standard Deviation 2.57
|
-0.4 Grams per liter (G/L)
Standard Deviation 2.78
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at indicated visit minus the Baseline value. Blood samples were collected for measurement. Hemoglobin and total protein were assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Hemoglobin and Total Protein at Month 6 and Month 12.
Hemoglobin, Month 6, n = 346, 113
|
2.3 Grams per liter (G/L)
Standard Deviation 5.33
|
1.9 Grams per liter (G/L)
Standard Deviation 5.54
|
|
Change From Baseline in Hemoglobin and Total Protein at Month 6 and Month 12.
Hemoglobin, Month 12, n = 339, 109
|
0.2 Grams per liter (G/L)
Standard Deviation 6.12
|
0.7 Grams per liter (G/L)
Standard Deviation 6.52
|
|
Change From Baseline in Hemoglobin and Total Protein at Month 6 and Month 12.
Total Protein, Month 6, n = 350, 114
|
0.4 Grams per liter (G/L)
Standard Deviation 3.30
|
0.3 Grams per liter (G/L)
Standard Deviation 3.34
|
|
Change From Baseline in Hemoglobin and Total Protein at Month 6 and Month 12.
Total Protein, Month 12, n = 340, 109
|
-0.2 Grams per liter (G/L)
Standard Deviation 3.57
|
-0.3 Grams per liter (G/L)
Standard Deviation 3.60
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Basophils, eosinophils, lymphocytes, monocytes, platelet count, total neutrophils-total ANC and white blood cell count were assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Eosinophils, Month 6, n = 346, 113
|
0.025 Giga per liter (GI/L)
Standard Deviation 0.1402
|
0.013 Giga per liter (GI/L)
Standard Deviation 0.1240
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Lymphocytes, Month 6, n = 346, 113
|
0.011 Giga per liter (GI/L)
Standard Deviation 0.3658
|
-0.020 Giga per liter (GI/L)
Standard Deviation 0.3513
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Lymphocytes, Month 12, n = 339, 109
|
-0.064 Giga per liter (GI/L)
Standard Deviation 0.3689
|
-0.082 Giga per liter (GI/L)
Standard Deviation 0.3584
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Platelet count, Month 6, n = 345, 113
|
3.0 Giga per liter (GI/L)
Standard Deviation 30.49
|
-0.1 Giga per liter (GI/L)
Standard Deviation 24.08
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
White Blood Cell count, Month 12, n = 339, 109
|
-0.14 Giga per liter (GI/L)
Standard Deviation 1.083
|
-0.20 Giga per liter (GI/L)
Standard Deviation 1.164
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Basophils, Month 6, n = 346, 113
|
-0.002 Giga per liter (GI/L)
Standard Deviation 0.0180
|
-0.001 Giga per liter (GI/L)
Standard Deviation 0.0180
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Basophils, Month 12, n = 339, 109
|
-0.001 Giga per liter (GI/L)
Standard Deviation 0.0160
|
-0.003 Giga per liter (GI/L)
Standard Deviation 0.0183
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Eosinophils, Month 12, n = 339, 109
|
-0.001 Giga per liter (GI/L)
Standard Deviation 0.1530
|
0.006 Giga per liter (GI/L)
Standard Deviation 0.1382
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Monocytes, Month 6, n = 346, 113
|
0.042 Giga per liter (GI/L)
Standard Deviation 0.0999
|
0.035 Giga per liter (GI/L)
Standard Deviation 0.0868
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Monocytes, Month 12, n = 339, 109
|
-0.007 Giga per liter (GI/L)
Standard Deviation 0.1002
|
-0.004 Giga per liter (GI/L)
Standard Deviation 0.0800
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Platelet count, Month 12, n = 337, 109
|
-6.8 Giga per liter (GI/L)
Standard Deviation 26.66
|
-3.6 Giga per liter (GI/L)
Standard Deviation 30.82
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Total ANC, Month 6, n = 346, 113
|
0.153 Giga per liter (GI/L)
Standard Deviation 1.0436
|
-0.002 Giga per liter (GI/L)
Standard Deviation 0.8814
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
Total ANC, Month 12, n = 339, 109
|
-0.071 Giga per liter (GI/L)
Standard Deviation 0.9412
|
-0.119 Giga per liter (GI/L)
Standard Deviation 0.9691
|
|
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils-total Absolute Neutrophil Count (ANC), White Blood Cell Count at Month 6 and Month 12.
White Blood Cell count, Month 6, n = 346, 113
|
0.23 Giga per liter (GI/L)
Standard Deviation 1.166
|
0.02 Giga per liter (GI/L)
Standard Deviation 1.036
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 6 and Month 12.Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Calcium (corrected) and calcium were assessed at Baseline, Month 1, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Calcium (Corrected), Calcium at Month 1, Month 6 and Month 12.
Calcium (corrected), Month 12, n = 340, 109
|
-0.002 Millimoles per liter (mmol/L)
Standard Deviation 0.0680
|
-0.001 Millimoles per liter (mmol/L)
Standard Deviation 0.0488
|
|
Change From Baseline in Calcium (Corrected), Calcium at Month 1, Month 6 and Month 12.
Calcium (corrected), Month 1, n = 365, 117
|
-0.063 Millimoles per liter (mmol/L)
Standard Deviation 0.0740
|
0.000 Millimoles per liter (mmol/L)
Standard Deviation 0.0505
|
|
Change From Baseline in Calcium (Corrected), Calcium at Month 1, Month 6 and Month 12.
Calcium, Month 1, n = 365, 117
|
-0.074 Millimoles per liter (mmol/L)
Standard Deviation 0.0906
|
-0.014 Millimoles per liter (mmol/L)
Standard Deviation 0.0614
|
|
Change From Baseline in Calcium (Corrected), Calcium at Month 1, Month 6 and Month 12.
Calcium, Month 12, n = 340, 109
|
0.002 Millimoles per liter (mmol/L)
Standard Deviation 0.0807
|
0.001 Millimoles per liter (mmol/L)
Standard Deviation 0.0648
|
|
Change From Baseline in Calcium (Corrected), Calcium at Month 1, Month 6 and Month 12.
Calcium (corrected), Month 6, n = 350, 114
|
-0.020 Millimoles per liter (mmol/L)
Standard Deviation 0.0704
|
-0.001 Millimoles per liter (mmol/L)
Standard Deviation 0.0537
|
|
Change From Baseline in Calcium (Corrected), Calcium at Month 1, Month 6 and Month 12.
Calcium, Month 6, n = 350, 114
|
-0.006 Millimoles per liter (mmol/L)
Standard Deviation 0.0809
|
0.009 Millimoles per liter (mmol/L)
Standard Deviation 0.0703
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Chloride, cholesterol, glucose, magnesium, inorganic phosphorous, potassium, sodium, triglycerides and urea/BUN were assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Chloride, Month 6, n = 350, 114
|
-0.9 Millimoles per liter (mmol/L)
Standard Deviation 2.48
|
-0.7 Millimoles per liter (mmol/L)
Standard Deviation 2.37
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Glucose, Month 12, n = 340, 109
|
0.16 Millimoles per liter (mmol/L)
Standard Deviation 0.124
|
-0.07 Millimoles per liter (mmol/L)
Standard Deviation 0.752
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Sodium, Month 12, n = 340, 109
|
-1.3 Millimoles per liter (mmol/L)
Standard Deviation 1.93
|
-0.7 Millimoles per liter (mmol/L)
Standard Deviation 1.76
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Triglycerides, Month 6, n = 350, 114
|
-0.082 Millimoles per liter (mmol/L)
Standard Deviation 0.7604
|
-0.000 Millimoles per liter (mmol/L)
Standard Deviation 0.6753
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Chloride, Month 12, n = 340, 109
|
0.4 Millimoles per liter (mmol/L)
Standard Deviation 2.17
|
0.6 Millimoles per liter (mmol/L)
Standard Deviation 2.34
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Cholesterol, Month 6, n = 350, 114
|
0.039 Millimoles per liter (mmol/L)
Standard Deviation 0.7626
|
0.057 Millimoles per liter (mmol/L)
Standard Deviation 0.7837
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Cholesterol, Month 12, n = 340, 109
|
0.047 Millimoles per liter (mmol/L)
Standard Deviation 0.8909
|
0.058 Millimoles per liter (mmol/L)
Standard Deviation 0.7889
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Glucose, Month 6, n = 350, 114
|
0.12 Millimoles per liter (mmol/L)
Standard Deviation 0.882
|
0.04 Millimoles per liter (mmol/L)
Standard Deviation 1.052
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Magnesium, Month 6, n = 350, 114
|
0.003 Millimoles per liter (mmol/L)
Standard Deviation 0.0523
|
-0.002 Millimoles per liter (mmol/L)
Standard Deviation 0.0547
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Magnesium, Month 12, n = 340, 109
|
0.013 Millimoles per liter (mmol/L)
Standard Deviation 0.0485
|
0.012 Millimoles per liter (mmol/L)
Standard Deviation 0.0572
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Phosphorus, inorganic, Month 6, n = 350, 114
|
-0.082 Millimoles per liter (mmol/L)
Standard Deviation 0.1440
|
-0.030 Millimoles per liter (mmol/L)
Standard Deviation 0.1353
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Phosphorus, inorganic, Month 12, n = 340, 109
|
-0.063 Millimoles per liter (mmol/L)
Standard Deviation 0.1520
|
-0.028 Millimoles per liter (mmol/L)
Standard Deviation 0.1304
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Potassium, Month 6, n = 350, 114
|
0.00 Millimoles per liter (mmol/L)
Standard Deviation 0.328
|
0.02 Millimoles per liter (mmol/L)
Standard Deviation 0.294
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Potassium, Month 12, n = 340, 109
|
0.01 Millimoles per liter (mmol/L)
Standard Deviation 0.300
|
-0.01 Millimoles per liter (mmol/L)
Standard Deviation 0.294
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Sodium, Month 6, n = 350, 114
|
-0.8 Millimoles per liter (mmol/L)
Standard Deviation 1.94
|
-0.4 Millimoles per liter (mmol/L)
Standard Deviation 2.24
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Triglycerides, Month 12, n = 340, 109
|
-0.014 Millimoles per liter (mmol/L)
Standard Deviation 0.9367
|
-0.029 Millimoles per liter (mmol/L)
Standard Deviation 0.7489
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Urea/BUN, Month 6, n = 350, 114
|
-0.18 Millimoles per liter (mmol/L)
Standard Deviation 1.045
|
-0.35 Millimoles per liter (mmol/L)
Standard Deviation 1.288
|
|
Change From Baseline in Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorous, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen (BUN) at Month 6 and Month 12.
Urea/BUN, Month 12, n = 340, 109
|
0.04 Millimoles per liter (mmol/L)
Standard Deviation 1.124
|
0.01 Millimoles per liter (mmol/L)
Standard Deviation 1.466
|
SECONDARY outcome
Timeframe: Baseline, Month 1, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Direct bilirubin and total bilirubin were assessed at Baseline, Month 1, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Direct Bilirubin, Total Bilirubin at Month 1, Month 6 and Month 12.
Direct Bilirubin, Month 12, n = 340, 109
|
0.1 Micromoles per liter (UMOL/L)
Standard Deviation 0.67
|
0.2 Micromoles per liter (UMOL/L)
Standard Deviation 0.68
|
|
Change From Baseline in Direct Bilirubin, Total Bilirubin at Month 1, Month 6 and Month 12.
Direct Bilirubin, Month 1, n = 365, 117
|
-0.1 Micromoles per liter (UMOL/L)
Standard Deviation 0.67
|
0.1 Micromoles per liter (UMOL/L)
Standard Deviation 0.52
|
|
Change From Baseline in Direct Bilirubin, Total Bilirubin at Month 1, Month 6 and Month 12.
Direct Bilirubin, Month 6, n = 350, 114
|
0.0 Micromoles per liter (UMOL/L)
Standard Deviation 0.72
|
0.1 Micromoles per liter (UMOL/L)
Standard Deviation 0.66
|
|
Change From Baseline in Direct Bilirubin, Total Bilirubin at Month 1, Month 6 and Month 12.
Total Bilirubin, Month 1, n = 365, 117
|
-0.3 Micromoles per liter (UMOL/L)
Standard Deviation 2.83
|
0.2 Micromoles per liter (UMOL/L)
Standard Deviation 2.61
|
|
Change From Baseline in Direct Bilirubin, Total Bilirubin at Month 1, Month 6 and Month 12.
Total Bilirubin, Month 6, n = 350, 114
|
0.1 Micromoles per liter (UMOL/L)
Standard Deviation 2.91
|
0.2 Micromoles per liter (UMOL/L)
Standard Deviation 2.66
|
|
Change From Baseline in Direct Bilirubin, Total Bilirubin at Month 1, Month 6 and Month 12.
Total Bilirubin, Month 12, n = 340, 109
|
0.3 Micromoles per liter (UMOL/L)
Standard Deviation 2.98
|
0.2 Micromoles per liter (UMOL/L)
Standard Deviation 2.80
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Creatinine and uric acid were assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Creatinine and Uric Acid at Month 6 and Month 12
Creatinine, Month 6, n = 350, 114
|
-0.47 Micromoles per liter (UMOL/L)
Standard Deviation 5.067
|
-0.90 Micromoles per liter (UMOL/L)
Standard Deviation 5.611
|
|
Change From Baseline in Creatinine and Uric Acid at Month 6 and Month 12
Creatinine, Month 12, n = 340, 109
|
-0.18 Micromoles per liter (UMOL/L)
Standard Deviation 5.116
|
-0.30 Micromoles per liter (UMOL/L)
Standard Deviation 6.185
|
|
Change From Baseline in Creatinine and Uric Acid at Month 6 and Month 12
Uric acid, Month 6, n = 350, 114
|
-8.9 Micromoles per liter (UMOL/L)
Standard Deviation 48.33
|
-8.9 Micromoles per liter (UMOL/L)
Standard Deviation 48.58
|
|
Change From Baseline in Creatinine and Uric Acid at Month 6 and Month 12
Uric acid, Month 12, n = 340, 109
|
-6.7 Micromoles per liter (UMOL/L)
Standard Deviation 49.84
|
-2.7 Micromoles per liter (UMOL/L)
Standard Deviation 44.85
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12.Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Hematocrit was assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Hematocrit at Month 6 and Month 12.
Hematocrit, Month 12, n = 339, 109
|
0.0064 Ratio
Standard Deviation 0.01884
|
0.0079 Ratio
Standard Deviation 0.01926
|
|
Change From Baseline in Hematocrit at Month 6 and Month 12.
Hematocrit, Month 6, n = 346, 113
|
0.0024 Ratio
Standard Deviation 0.01612
|
0.0012 Ratio
Standard Deviation 0.01662
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12.Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in Baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Mean corpuscle hemoglobin was assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 and Month 12.
Mean Corpuscle Hemoglobin, Month 6, n = 346, 113
|
0.22 Picograms (PG)
Standard Deviation 0.599
|
0.18 Picograms (PG)
Standard Deviation 0.561
|
|
Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 and Month 12.
Mean Corpuscle Hemoglobin, Month 12, n = 339, 109
|
-0.31 Picograms (PG)
Standard Deviation 0.691
|
-0.38 Picograms (PG)
Standard Deviation 0.600
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at Screening (Visit 2). If missing, the most recent non-missing value was used. Change in baseline value was assessed as the value at the indicated visit minus the Baseline value. Blood samples were collected for measurement. Mean corpuscle volume was assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Mean Corpuscle Volume at Month 6 and Month 12.
Mean Corpuscle Volume, Month 6, n = 346, 113
|
-0.4 Femtoliter (FL)
Standard Deviation 1.77
|
-0.5 Femtoliter (FL)
Standard Deviation 2.17
|
|
Change From Baseline in Mean Corpuscle Volume at Month 6 and Month 12.
Mean Corpuscle Volume, Month 12, n = 339, 109
|
0.4 Femtoliter (FL)
Standard Deviation 2.01
|
0.3 Femtoliter (FL)
Standard Deviation 1.77
|
SECONDARY outcome
Timeframe: Baseline, Month 6 and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Baseline value was obtained at screening (visit 2). If missing, the most recent non-missing value was used. Change in baseline value was assessed as: Value at Indicated visit minus Baseline value. Blood samples were collected for measurement. Red blood cell count was assessed at Baseline, Month 6 and Month 12.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Change From Baseline in Red Blood Cell Count at Month 6 and Month 12
Red Blood Cell count, Month 12, n = 339, 109
|
0.05 Trillion cells per liter (TI/L)
Standard Deviation 0.203
|
0.07 Trillion cells per liter (TI/L)
Standard Deviation 0.200
|
|
Change From Baseline in Red Blood Cell Count at Month 6 and Month 12
Red Blood Cell count, Month 6, n = 346, 113
|
0.04 Trillion cells per liter (TI/L)
Standard Deviation 0.180
|
0.04 Trillion cells per liter (TI/L)
Standard Deviation 0.170
|
SECONDARY outcome
Timeframe: Baseline and Month 12Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Anti-denosumab antibody formation was assessed at Baseline (Visit 3) and Month 12. Binding antibody and neutralizing antibody assays were used to assess number of participants with anti-denosumab antibody.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Number of Participants With Confirmed Anti-denosumab Antibody Formation at Baseline and Month 12
Binding antibody detection, Baseline, n = 15, 3
|
0 Participants
|
0 Participants
|
|
Number of Participants With Confirmed Anti-denosumab Antibody Formation at Baseline and Month 12
Binding antibody detection, Month 12, n = 29, 3
|
1 Participants
|
0 Participants
|
|
Number of Participants With Confirmed Anti-denosumab Antibody Formation at Baseline and Month 12
Neutralising antibody detection,Month 12, n = 1,0
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months)Population: Safety Population. Two participants randomized to placebo group received denosumab by mistake.
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or other events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcome listed above, liver injury and impaired liver function and grade 4 laboratory abnormalities. Number of participants with any AEs, serious non-fatal AEs, serious fatal AEs have been presented.
Outcome measures
| Measure |
Denosumab 60 mg
n=367 Participants
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 Participants
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (Non-fatal Serious Adverse Events and Fatal Serious Adverse Events)
Any Serious Non-Fatal AEs
|
9 Participants
|
3 Participants
|
|
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (Non-fatal Serious Adverse Events and Fatal Serious Adverse Events)
Any AEs
|
174 Participants
|
63 Participants
|
|
Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (Non-fatal Serious Adverse Events and Fatal Serious Adverse Events)
Any Serious Fatal AEs
|
2 Participants
|
0 Participants
|
Adverse Events
Denosumab 60mg
Placebo
Serious adverse events
| Measure |
Denosumab 60mg
n=367 participants at risk
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 participants at risk
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Cardiac disorders
Coronary artery disease
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Injury, poisoning and procedural complications
Any event
|
0.82%
3/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.85%
1/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.54%
2/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.85%
1/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Cardiac disorders
Any event
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
1.7%
2/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.85%
1/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.85%
1/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.00%
0/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.85%
1/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.85%
1/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Infections and infestations
Any event
|
0.54%
2/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Infections and infestations
Bronchitis
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Infections and infestations
Erysipelas
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Any event
|
0.82%
3/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Musculoskeletal and connective tissue disorders
Any event
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Nervous system disorders
Any event
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Nervous system disorders
Brain stem infarction
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
General disorders
Any event
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
General disorders
Sudden cardiac death
|
0.27%
1/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
Other adverse events
| Measure |
Denosumab 60mg
n=367 participants at risk
Participants received single subcutaneous (SC) injection of denosumab 60 milligrams (mg) at Baseline and Month 6 during the Double-blind Treatment Phase. Particpants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 international unit \[IU\]).
|
Placebo
n=117 participants at risk
Participants received single SC injection of placebo at Baseline and Month 6 during the Double-blind Treatment Phase. Participants also received daily oral supplementation of elemental calcium (at least 600 mg) and vitamin D (at least 400 IU).
|
|---|---|---|
|
Investigations
Arthralgia
|
6.5%
24/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
7.7%
9/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Investigations
Blood cholesterol increased
|
5.2%
19/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
9.4%
11/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
|
Investigations
Bone density decreased
|
0.54%
2/367 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
5.1%
6/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of IP through the Study Phase (6 months post-dose) (assessed up to 12 months).
On-treatment SAEs and non-serious AEs are reported for safety population, comprised of all participants randomized to treatment who received at least one dose of IP.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER