Trial Outcomes & Findings for Efficacy in Reducing Fractures and Safety of Zoledronic Acid in Men With Osteoporosis (NCT NCT00439647)
NCT ID: NCT00439647
Last Updated: 2017-04-21
Results Overview
Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1199 participants
Primary outcome timeframe
24 Months
Results posted on
2017-04-21
Participant Flow
Participant milestones
| Measure |
Zoledronic Acid
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Overall Study
STARTED
|
588
|
611
|
|
Overall Study
Modified Intent to Treat (mITT)
|
553
|
574
|
|
Overall Study
COMPLETED
|
530
|
540
|
|
Overall Study
NOT COMPLETED
|
58
|
71
|
Reasons for withdrawal
| Measure |
Zoledronic Acid
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
25
|
22
|
|
Overall Study
Death
|
15
|
18
|
|
Overall Study
Adverse Event
|
11
|
11
|
|
Overall Study
Lost to Follow-up
|
4
|
12
|
|
Overall Study
Protocol Violation
|
3
|
4
|
|
Overall Study
Lack of Efficacy
|
0
|
4
|
Baseline Characteristics
Efficacy in Reducing Fractures and Safety of Zoledronic Acid in Men With Osteoporosis
Baseline characteristics by cohort
| Measure |
Zoledronic Acid
n=588 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=611 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Total
n=1199 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.8 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
65.7 years
STANDARD_DEVIATION 8.6 • n=7 Participants
|
65.8 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
588 Participants
n=5 Participants
|
611 Participants
n=7 Participants
|
1199 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 MonthsPopulation: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. In this analysis, missing Month 24 fractures were imputed using LOCF.
Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height
Outcome measures
| Measure |
Zoledronic Acid
n=553 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=574 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months
|
1.6 Percentage of Participants
|
4.9 Percentage of Participants
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height
Outcome measures
| Measure |
Zoledronic Acid
n=553 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=574 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 12 Months
|
0.9 Percentage of participants
|
2.8 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height.
Outcome measures
| Measure |
Zoledronic Acid
n=553 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=574 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months
|
0.4 Percentage of participants
|
1.9 Percentage of participants
|
SECONDARY outcome
Timeframe: 24 MonthsPopulation: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height.
Outcome measures
| Measure |
Zoledronic Acid
n=553 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=574 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 24 Months
|
1.1 Percentage of participants
|
3.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 12 monthsPopulation: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
Worsening vertebral fracture (VF) was assessed based on morphometry. QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit, x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture)
Outcome measures
| Measure |
Zoledronic Acid
n=553 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=574 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 12 Months
|
1.3 Percentage of Participants
|
2.8 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline, Month 24Population: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. In this analysis, missing Month 24 fractures were imputed using LOCF.
Worsening vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture)
Outcome measures
| Measure |
Zoledronic Acid
n=553 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=574 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 24 Months
|
2.0 Percentage of Participants
|
4.9 Percentage of Participants
|
SECONDARY outcome
Timeframe: from Baseline to 12 months and 24 monthsPopulation: Modified Intent-to-treat (mITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the primary efficacy variable. Patients with a baseline x-ray and a 12M x-ray are included.
Height was measured using a stadiometer. Two measurements were taken in millimeters (mm), and repeated if the two measurements differed by greater than 4 mm. The average of the two (or four) height measurements was used for analysis
Outcome measures
| Measure |
Zoledronic Acid
n=529 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=547 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Mean Change in Height From Baseline
12 months
|
-0.86 mm
Standard Error 0.333
|
-2.50 mm
Standard Error 0.522
|
|
Mean Change in Height From Baseline
24 months
|
-2.33 mm
Standard Error 0.389
|
-4.61 mm
Standard Error 0.610
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: The ITT (intent to treat) population consisted of all subjects as randomized.
Clinical vertebral fracture is a painful vertebral fracture which came to clinical attention, e.g., with increased back pain, impairment of mobility or functional limitations. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier.
Outcome measures
| Measure |
Zoledronic Acid
n=588 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=611 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Number of Participants With First Clinical Vertebral Fracture
|
1 Participants
NA
|
3 Participants
1.63
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: The ITT (intent to treat) population consisted of all subjects as randomized.
Clinical fracture is painful fracture in any site which came to clinical attention, e.g., with increased pain, impaired mobility or functional limitations. Subjects who did not experience fracture were censored at end of study. End of study was defined as the earlier of last visit or date of death.
Outcome measures
| Measure |
Zoledronic Acid
n=588 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=611 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Number of Participants With First Clinical Fracture
|
6 Participants
1.95
|
11 Participants
3.09
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: The ITT (intent to treat) population consisted of all subjects as randomized.
Non-vertebral fracture is any fracture which was not of the vertebrae. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier.
Outcome measures
| Measure |
Zoledronic Acid
n=588 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=611 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Number of Participants With First Non-vertebral Fracture
|
5 Participants
1.88
|
8 Participants
2.83
|
SECONDARY outcome
Timeframe: Month 6, Month 12, Month 24Population: Intent-to-treat (ITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the efficacy variable.
Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in BMD at lumbar spine at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline)
Outcome measures
| Measure |
Zoledronic Acid
n=65 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=63 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD)
Month 6 (n=61, n=61)
|
4.87 Percent change in BMD
Standard Error 0.412
|
0.10 Percent change in BMD
Standard Error 0.412
|
|
Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD)
Month 12 (n=60, n=62)
|
5.51 Percent change in BMD
Standard Error 0.437
|
0.84 Percent change in BMD
Standard Error 0.430
|
|
Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD)
Month 24 (n=58, n=61)
|
7.73 Percent change in BMD
Standard Error 0.459
|
1.61 Percent change in BMD
Standard Error 0.448
|
SECONDARY outcome
Timeframe: Month 6, Month 12, Month 24Population: Intent-to-treat (ITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the efficacy variable.
Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total hip BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline)
Outcome measures
| Measure |
Zoledronic Acid
n=64 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=65 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage Change From Baseline in Total Hip BMD (g/CM^2)
Month 6 (n=60, n=63)
|
1.38 Percent change in BMD
Standard Error 0.294
|
-0.44 Percent change in BMD
Standard Error 0.287
|
|
Percentage Change From Baseline in Total Hip BMD (g/CM^2)
Month 12 (n=58, n=64)
|
1.66 Percent change in BMD
Standard Error 0.283
|
0.26 Percent change in BMD
Standard Error 0.269
|
|
Percentage Change From Baseline in Total Hip BMD (g/CM^2)
Month 24 (n=56, n=63)
|
2.31 Percent change in BMD
Standard Error 0.346
|
0.16 Percent change in BMD
Standard Error 0.326
|
SECONDARY outcome
Timeframe: Month 6, Month 12, Month 24Population: Intent-to-treat (ITT) population included all randomized subjects who had a baseline and at least one post-baseline assessment of the efficacy variable.
Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total femoral neck BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100\*(endpoint - baseline)
Outcome measures
| Measure |
Zoledronic Acid
n=64 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=65 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Percentage Change From Baseline in Femoral Neck BMD (g/CM^2)
Month 6 (n=60, n=63)
|
2.21 Percent change in BMD
Standard Error 0.448
|
0.58 Percent change in BMD
Standard Error 0.437
|
|
Percentage Change From Baseline in Femoral Neck BMD (g/CM^2)
Month 12 (n=58, n=64)
|
2.06 Percent change in BMD
Standard Error 0.465
|
0.59 Percent change in BMD
Standard Error 0.443
|
|
Percentage Change From Baseline in Femoral Neck BMD (g/CM^2)
Month 24 (n=56, n=63)
|
3.39 Percent change in BMD
Standard Error 0.544
|
0.09 Percent change in BMD
Standard Error 0.513
|
SECONDARY outcome
Timeframe: Baseline, Month 3, Month 6, Month 12, Month 15, month 18, Month 24Population: The ITT, Intent to Treat population, includes all participants who received a single a dose of treatment and had data available for analysis. n = the number of subjects with evaluable measurements at visit, as determined by the efficacy window.
Outcome measures
| Measure |
Zoledronic Acid
n=64 Participants
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
Placebo
n=66 Participants
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year.
|
|---|---|---|
|
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Baseline (n-64) (n=66)
|
0.3646 ng/mL
Standard Error 0.02094
|
0.3933 ng/mL
Standard Error 0.02955
|
|
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Month 3 (n=63) (n=65)
|
0.0990 ng/mL
Standard Error 0.00800 • Interval 0.22 to 0.31
|
0.3647 ng/mL
Standard Error 0.02989 • Interval 0.22 to 0.31
|
|
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Month 6 (n=62) (n=64)
|
0.1384 ng/mL
Standard Error 0.00914 • Interval 0.34 to 0.47
|
0.3540 ng/mL
Standard Error 0.02576 • Interval 0.34 to 0.47
|
|
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Month 12 (n=63) (n=64)
|
0.1669 ng/mL
Standard Error 0.00925 • Interval 0.38 to 0.53
|
0.4042 ng/mL
Standard Error 0.03056 • Interval 0.38 to 0.53
|
|
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Month 15 (n=55) (n=58)
|
0.0996 ng/mL
Standard Error 0.00590
|
0.3576 ng/mL
Standard Error 0.02519
|
|
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Month 18 (n=55) (n=60)
|
0.1320 ng/mL
Standard Error 0.00661
|
0.3954 ng/mL
Standard Error 0.03001
|
|
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Month 24 (n=55) (n=62)
|
0.1760 ng/mL
Standard Error 0.01248 • Interval 0.38 to 0.52
|
0.4060 ng/mL
Standard Error 0.02640 • Interval 0.38 to 0.52
|
Adverse Events
Zoledronic Acid
Serious events: 149 serious events
Other events: 399 other events
Deaths: 0 deaths
Placebo
Serious events: 154 serious events
Other events: 256 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Zoledronic Acid
n=588 participants at risk
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The i.v. infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year
|
Placebo
n=611 participants at risk
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The i.v. infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.17%
1/588
|
0.16%
1/611
|
|
Blood and lymphatic system disorders
Bone marrow failure
|
0.00%
0/588
|
0.16%
1/611
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/588
|
0.16%
1/611
|
|
Blood and lymphatic system disorders
Pernicious anaemia
|
0.17%
1/588
|
0.00%
0/611
|
|
Cardiac disorders
Acute myocardial infarction
|
0.85%
5/588
|
0.16%
1/611
|
|
Cardiac disorders
Angina pectoris
|
1.0%
6/588
|
1.1%
7/611
|
|
Cardiac disorders
Angina unstable
|
0.34%
2/588
|
0.00%
0/611
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/588
|
0.33%
2/611
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.17%
1/588
|
0.00%
0/611
|
|
Cardiac disorders
Atrial fibrillation
|
1.2%
7/588
|
0.82%
5/611
|
|
Cardiac disorders
Atrial flutter
|
0.17%
1/588
|
0.00%
0/611
|
|
Cardiac disorders
Cardiac arrest
|
0.17%
1/588
|
0.33%
2/611
|
|
Cardiac disorders
Cardiac failure
|
0.17%
1/588
|
0.65%
4/611
|
|
Cardiac disorders
Cardiac failure chronic
|
0.00%
0/588
|
0.16%
1/611
|
|
Cardiac disorders
Cardiac failure congestive
|
0.17%
1/588
|
0.16%
1/611
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/588
|
0.16%
1/611
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/588
|
0.16%
1/611
|
|
Cardiac disorders
Cardiovascular insufficiency
|
0.17%
1/588
|
0.00%
0/611
|
|
Cardiac disorders
Coronary artery disease
|
0.17%
1/588
|
0.33%
2/611
|
|
Cardiac disorders
Coronary artery stenosis
|
0.17%
1/588
|
0.16%
1/611
|
|
Cardiac disorders
Mitral valve incompetence
|
0.00%
0/588
|
0.16%
1/611
|
|
Cardiac disorders
Myocardial infarction
|
0.68%
4/588
|
0.16%
1/611
|
|
Cardiac disorders
Myocardial ischaemia
|
0.51%
3/588
|
0.16%
1/611
|
|
Cardiac disorders
Myocarditis
|
0.17%
1/588
|
0.00%
0/611
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/588
|
0.16%
1/611
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/588
|
0.16%
1/611
|
|
Congenital, familial and genetic disorders
Exomphalos
|
0.17%
1/588
|
0.00%
0/611
|
|
Congenital, familial and genetic disorders
Phimosis
|
0.17%
1/588
|
0.00%
0/611
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.00%
0/588
|
0.16%
1/611
|
|
Ear and labyrinth disorders
Vertigo
|
0.51%
3/588
|
0.16%
1/611
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/588
|
0.16%
1/611
|
|
Eye disorders
Cataract
|
0.00%
0/588
|
0.16%
1/611
|
|
Eye disorders
Heterophoria
|
0.00%
0/588
|
0.16%
1/611
|
|
Eye disorders
Retinal degeneration
|
0.17%
1/588
|
0.00%
0/611
|
|
Eye disorders
Retinal detachment
|
0.00%
0/588
|
0.33%
2/611
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/588
|
0.33%
2/611
|
|
Gastrointestinal disorders
Anal haemorrhage
|
0.17%
1/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Constipation
|
0.17%
1/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/588
|
0.49%
3/611
|
|
Gastrointestinal disorders
Diverticular perforation
|
0.17%
1/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.34%
2/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Enterovesical fistula
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Femoral hernia
|
0.17%
1/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/588
|
0.33%
2/611
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.17%
1/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Haematemesis
|
0.17%
1/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.17%
1/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Ileus
|
0.17%
1/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.51%
3/588
|
0.33%
2/611
|
|
Gastrointestinal disorders
Inguinal hernia, obstructive
|
0.17%
1/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Intestinal congestion
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Melaena
|
0.17%
1/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Oesophagitis
|
0.34%
2/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.34%
2/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Pancreatitis chronic
|
0.17%
1/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Peritonitis
|
0.34%
2/588
|
0.00%
0/611
|
|
Gastrointestinal disorders
Poor dental condition
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/588
|
0.33%
2/611
|
|
Gastrointestinal disorders
Rectal polyp
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Reflux oesophagitis
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/588
|
0.16%
1/611
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/588
|
0.16%
1/611
|
|
General disorders
Adverse drug reaction
|
0.17%
1/588
|
0.00%
0/611
|
|
General disorders
Asthenia
|
0.00%
0/588
|
0.16%
1/611
|
|
General disorders
Chest pain
|
0.17%
1/588
|
0.33%
2/611
|
|
General disorders
Death
|
0.17%
1/588
|
0.33%
2/611
|
|
General disorders
Device failure
|
0.17%
1/588
|
0.00%
0/611
|
|
General disorders
Device occlusion
|
0.00%
0/588
|
0.33%
2/611
|
|
General disorders
Impaired healing
|
0.00%
0/588
|
0.16%
1/611
|
|
General disorders
Malaise
|
0.17%
1/588
|
0.16%
1/611
|
|
General disorders
Non-cardiac chest pain
|
0.51%
3/588
|
0.00%
0/611
|
|
General disorders
Pyrexia
|
0.00%
0/588
|
0.33%
2/611
|
|
General disorders
Sudden death
|
0.17%
1/588
|
0.16%
1/611
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/588
|
0.16%
1/611
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.51%
3/588
|
0.16%
1/611
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.34%
2/588
|
0.65%
4/611
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/588
|
0.16%
1/611
|
|
Hepatobiliary disorders
Jaundice
|
0.17%
1/588
|
0.00%
0/611
|
|
Immune system disorders
Hypersensitivity
|
0.17%
1/588
|
0.00%
0/611
|
|
Infections and infestations
Abdominal abscess
|
0.17%
1/588
|
0.00%
0/611
|
|
Infections and infestations
Anal abscess
|
0.00%
0/588
|
0.16%
1/611
|
|
Infections and infestations
Appendicitis
|
0.34%
2/588
|
0.16%
1/611
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/588
|
0.16%
1/611
|
|
Infections and infestations
Chronic sinusitis
|
0.17%
1/588
|
0.00%
0/611
|
|
Infections and infestations
Device related infection
|
0.17%
1/588
|
0.00%
0/611
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/588
|
0.16%
1/611
|
|
Infections and infestations
Gastroenteritis
|
0.17%
1/588
|
0.16%
1/611
|
|
Infections and infestations
Gastroenteritis viral
|
0.17%
1/588
|
0.16%
1/611
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/588
|
0.16%
1/611
|
|
Infections and infestations
Incision site abscess
|
0.00%
0/588
|
0.16%
1/611
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.17%
1/588
|
0.00%
0/611
|
|
Infections and infestations
Lung infection
|
0.00%
0/588
|
0.16%
1/611
|
|
Infections and infestations
Osteomyelitis
|
0.17%
1/588
|
0.00%
0/611
|
|
Infections and infestations
Pneumonia
|
1.0%
6/588
|
1.5%
9/611
|
|
Infections and infestations
Pyelonephritis
|
0.17%
1/588
|
0.16%
1/611
|
|
Infections and infestations
Respiratory tract infection
|
0.17%
1/588
|
0.16%
1/611
|
|
Infections and infestations
Sepsis
|
0.17%
1/588
|
0.00%
0/611
|
|
Infections and infestations
Tracheobronchitis
|
0.00%
0/588
|
0.16%
1/611
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/588
|
0.65%
4/611
|
|
Infections and infestations
Vestibular neuronitis
|
0.17%
1/588
|
0.00%
0/611
|
|
Infections and infestations
Viral infection
|
0.17%
1/588
|
0.00%
0/611
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.00%
0/588
|
0.16%
1/611
|
|
Injury, poisoning and procedural complications
Arterial injury
|
0.17%
1/588
|
0.00%
0/611
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/588
|
0.16%
1/611
|
|
Injury, poisoning and procedural complications
Fall
|
0.51%
3/588
|
0.16%
1/611
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.17%
1/588
|
0.00%
0/611
|
|
Injury, poisoning and procedural complications
Injury
|
0.17%
1/588
|
0.00%
0/611
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.34%
2/588
|
0.00%
0/611
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.00%
0/588
|
0.16%
1/611
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.17%
1/588
|
0.00%
0/611
|
|
Injury, poisoning and procedural complications
Pneumothorax traumatic
|
0.17%
1/588
|
0.16%
1/611
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/588
|
0.49%
3/611
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/588
|
0.16%
1/611
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.17%
1/588
|
0.16%
1/611
|
|
Injury, poisoning and procedural complications
Traumatic fracture
|
2.7%
16/588
|
1.6%
10/611
|
|
Injury, poisoning and procedural complications
Traumatic lung injury
|
0.17%
1/588
|
0.00%
0/611
|
|
Injury, poisoning and procedural complications
Vascular graft complication
|
0.17%
1/588
|
0.00%
0/611
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/588
|
0.16%
1/611
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.17%
1/588
|
0.16%
1/611
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.17%
1/588
|
0.00%
0/611
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/588
|
0.49%
3/611
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.17%
1/588
|
0.00%
0/611
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
0.00%
0/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.34%
2/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Bunion
|
0.00%
0/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
0.00%
0/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.17%
1/588
|
0.00%
0/611
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
1.2%
7/588
|
0.49%
3/611
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.17%
1/588
|
0.00%
0/611
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.17%
1/588
|
0.00%
0/611
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.68%
4/588
|
0.82%
5/611
|
|
Musculoskeletal and connective tissue disorders
Pseudarthrosis
|
0.17%
1/588
|
0.33%
2/611
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.17%
1/588
|
0.00%
0/611
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.34%
2/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Sensation of heaviness
|
0.34%
2/588
|
0.00%
0/611
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.17%
1/588
|
0.00%
0/611
|
|
Musculoskeletal and connective tissue disorders
Spondyloarthropathy
|
0.00%
0/588
|
0.16%
1/611
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.68%
4/588
|
0.33%
2/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer stage 0, with cancer in situ
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm benign
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.17%
1/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.17%
1/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal carcinoma
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma
|
0.17%
1/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
0.34%
2/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hypopharyngeal cancer
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.17%
1/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymph node cancer metastatic
|
0.17%
1/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.17%
1/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.00%
0/588
|
0.33%
2/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lymph nodes
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to the mediastinum
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma
|
0.17%
1/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal neoplasm
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
1.0%
6/588
|
0.65%
4/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic
|
0.17%
1/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
0.00%
0/588
|
0.33%
2/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.17%
1/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.17%
1/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer extensive stage
|
0.00%
0/588
|
0.16%
1/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.17%
1/588
|
0.00%
0/611
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid adenoma
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Alcohol induced persisting dementia
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Balance disorder
|
0.17%
1/588
|
0.16%
1/611
|
|
Nervous system disorders
Brain compression
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Carotid artery stenosis
|
0.34%
2/588
|
0.00%
0/611
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.17%
1/588
|
0.00%
0/611
|
|
Nervous system disorders
Cerebellar infarction
|
0.17%
1/588
|
0.00%
0/611
|
|
Nervous system disorders
Cerebral atrophy
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Cerebral infarction
|
0.17%
1/588
|
0.16%
1/611
|
|
Nervous system disorders
Cerebral ischaemia
|
0.17%
1/588
|
0.00%
0/611
|
|
Nervous system disorders
Cerebrovascular accident
|
1.0%
6/588
|
0.82%
5/611
|
|
Nervous system disorders
Cerebrovascular insufficiency
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Cervical root pain
|
0.17%
1/588
|
0.00%
0/611
|
|
Nervous system disorders
Coma
|
0.17%
1/588
|
0.00%
0/611
|
|
Nervous system disorders
Convulsion
|
0.17%
1/588
|
0.16%
1/611
|
|
Nervous system disorders
Dementia
|
0.17%
1/588
|
0.16%
1/611
|
|
Nervous system disorders
Dizziness
|
0.17%
1/588
|
0.16%
1/611
|
|
Nervous system disorders
Encephalitis
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Headache
|
0.34%
2/588
|
0.00%
0/611
|
|
Nervous system disorders
Hemiparesis
|
0.17%
1/588
|
0.16%
1/611
|
|
Nervous system disorders
Hypoglycaemic coma
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Hypoxic-ischaemic encephalopathy
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Intracranial aneurysm
|
0.17%
1/588
|
0.00%
0/611
|
|
Nervous system disorders
Ischaemic stroke
|
0.34%
2/588
|
0.00%
0/611
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Monoparesis
|
0.17%
1/588
|
0.00%
0/611
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Parkinson's disease
|
0.00%
0/588
|
0.16%
1/611
|
|
Nervous system disorders
Radicular pain
|
0.17%
1/588
|
0.00%
0/611
|
|
Nervous system disorders
Syncope
|
0.17%
1/588
|
0.33%
2/611
|
|
Nervous system disorders
Transient ischaemic attack
|
0.68%
4/588
|
0.49%
3/611
|
|
Psychiatric disorders
Depression
|
0.17%
1/588
|
0.00%
0/611
|
|
Psychiatric disorders
Encopresis
|
0.17%
1/588
|
0.00%
0/611
|
|
Psychiatric disorders
Panic attack
|
0.17%
1/588
|
0.00%
0/611
|
|
Renal and urinary disorders
Bladder neck obstruction
|
0.17%
1/588
|
0.00%
0/611
|
|
Renal and urinary disorders
Calculus ureteric
|
0.34%
2/588
|
0.00%
0/611
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/588
|
0.16%
1/611
|
|
Renal and urinary disorders
Haematuria
|
0.17%
1/588
|
0.16%
1/611
|
|
Renal and urinary disorders
Microalbuminuria
|
0.00%
0/588
|
0.16%
1/611
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.51%
3/588
|
0.33%
2/611
|
|
Renal and urinary disorders
Renal artery stenosis
|
0.00%
0/588
|
0.16%
1/611
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/588
|
0.16%
1/611
|
|
Renal and urinary disorders
Renal failure
|
0.17%
1/588
|
0.00%
0/611
|
|
Renal and urinary disorders
Renal failure acute
|
0.17%
1/588
|
0.00%
0/611
|
|
Renal and urinary disorders
Urethral polyp
|
0.17%
1/588
|
0.00%
0/611
|
|
Renal and urinary disorders
Urethral stenosis
|
0.17%
1/588
|
0.00%
0/611
|
|
Renal and urinary disorders
Urinary retention
|
0.51%
3/588
|
0.49%
3/611
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.34%
2/588
|
0.49%
3/611
|
|
Reproductive system and breast disorders
Epididymal cyst
|
0.00%
0/588
|
0.16%
1/611
|
|
Reproductive system and breast disorders
Epididymitis
|
0.00%
0/588
|
0.16%
1/611
|
|
Reproductive system and breast disorders
Prostatomegaly
|
0.17%
1/588
|
0.00%
0/611
|
|
Reproductive system and breast disorders
Testicular swelling
|
0.00%
0/588
|
0.16%
1/611
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/588
|
0.16%
1/611
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.17%
1/588
|
0.00%
0/611
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.17%
1/588
|
0.00%
0/611
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.68%
4/588
|
1.1%
7/611
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.34%
2/588
|
0.00%
0/611
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.68%
4/588
|
0.65%
4/611
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.17%
1/588
|
0.00%
0/611
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.00%
0/588
|
0.16%
1/611
|
|
Respiratory, thoracic and mediastinal disorders
Foreign body aspiration
|
0.00%
0/588
|
0.16%
1/611
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.17%
1/588
|
0.00%
0/611
|
|
Respiratory, thoracic and mediastinal disorders
Lung consolidation
|
0.17%
1/588
|
0.00%
0/611
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.17%
1/588
|
0.16%
1/611
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.17%
1/588
|
0.00%
0/611
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.17%
1/588
|
0.00%
0/611
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/588
|
0.33%
2/611
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.17%
1/588
|
0.33%
2/611
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.17%
1/588
|
0.16%
1/611
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.00%
0/588
|
0.16%
1/611
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/588
|
0.16%
1/611
|
|
Social circumstances
Walking disability
|
0.17%
1/588
|
0.00%
0/611
|
|
Vascular disorders
Aortic aneurysm
|
0.34%
2/588
|
0.16%
1/611
|
|
Vascular disorders
Arterial haemorrhage
|
0.00%
0/588
|
0.16%
1/611
|
|
Vascular disorders
Arteriosclerosis
|
0.17%
1/588
|
0.16%
1/611
|
|
Vascular disorders
Arteritis
|
0.00%
0/588
|
0.16%
1/611
|
|
Vascular disorders
Deep vein thrombosis
|
0.17%
1/588
|
0.00%
0/611
|
|
Vascular disorders
Femoral arterial stenosis
|
0.00%
0/588
|
0.16%
1/611
|
|
Vascular disorders
Hypertension
|
0.51%
3/588
|
0.49%
3/611
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/588
|
0.16%
1/611
|
|
Vascular disorders
Hypovolaemic shock
|
0.17%
1/588
|
0.16%
1/611
|
|
Vascular disorders
Intermittent claudication
|
0.17%
1/588
|
0.16%
1/611
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
0.00%
0/588
|
0.16%
1/611
|
|
Vascular disorders
Peripheral artery aneurysm
|
0.00%
0/588
|
0.16%
1/611
|
|
Vascular disorders
Peripheral ischaemia
|
0.34%
2/588
|
0.33%
2/611
|
|
Vascular disorders
Varicose vein
|
0.00%
0/588
|
0.16%
1/611
|
|
Vascular disorders
Vascular calcification
|
0.00%
0/588
|
0.16%
1/611
|
|
Vascular disorders
Venous insufficiency
|
0.00%
0/588
|
0.16%
1/611
|
Other adverse events
| Measure |
Zoledronic Acid
n=588 participants at risk
5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The i.v. infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year
|
Placebo
n=611 participants at risk
100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The i.v. infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year
|
|---|---|---|
|
General disorders
Chills
|
6.8%
40/588
|
0.82%
5/611
|
|
General disorders
Fatigue
|
6.8%
40/588
|
2.1%
13/611
|
|
General disorders
Influenza like illness
|
5.1%
30/588
|
2.3%
14/611
|
|
General disorders
Pyrexia
|
24.3%
143/588
|
3.4%
21/611
|
|
Infections and infestations
Influenza
|
5.1%
30/588
|
4.6%
28/611
|
|
Infections and infestations
Nasopharyngitis
|
8.5%
50/588
|
8.0%
49/611
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.9%
123/588
|
10.6%
65/611
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.9%
82/588
|
11.9%
73/611
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.1%
30/588
|
3.1%
19/611
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
21.9%
129/588
|
4.1%
25/611
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.3%
43/588
|
3.8%
23/611
|
|
Nervous system disorders
Headache
|
13.6%
80/588
|
4.4%
27/611
|
|
Vascular disorders
Hypertension
|
8.0%
47/588
|
7.0%
43/611
|
Additional Information
Novartis Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial; or the publication of the trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER