Post-menopausal Osteoporosis
Conditions
Keywords
Osteoporosis, zoledronic acid, post-menopausal
Brief summary
This second extension will evaluate the efficacy and long term safety of zoledronic acid in women with post-menopausal osteoporosis
Interventions
DRUGPlacebo
DRUGZoledronic acid
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women who have received the 4th and 6th dose of zoledronic acid in study CZOL446H2301E1
Exclusion criteria
* Poor kidney, eye, liver health * Use of certain therapies for osteoporosis in study CZOL446H2301E1 * Abnormal calcium levels Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Total Hip Bone Mineral Density BMD at Year 6 (Baseline) and Year 9 | Year 6 (baseline) and Year 9 | Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 6 = 100\*(Year 9 - Year 6)/Year 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7 and 8 Compared to Year 6 | Year 6 (extension 2 baseline), Year 7, Year 8 | Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 6 = 100\*(Year 9 - Year 6)/Year 6. |
| Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6 | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 6 = 100\*(Year 9 - Year 6)/Year 6. |
| Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 0 (core baseline), Year 7, Year 8, Year 9 | Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 0 = 100\*(Year 9 - Year 0)/Year 0. |
| Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 0 (core baseline), Year 7, Year 8, Year 9 | Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 0 = 100\*(Year 9 - Year 0)/Year 0. |
| Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | Bone marker analysis: All patients had blood samples collected for analysis of serum c-terminal telopeptide of type I collagen (CTx). Serum CTX assays measure a fragment of the C-terminal telopeptide of type 1 collagen released during resorption of mature bone |
| Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | Bone marker analysis: All patients had blood samples collected for analysis of serum n-terminal propeptide of type I collagen (P1NP) The P1NP concentration is directly proportional to the amount of new collagen laid down during bone formation. |
| Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | Bone marker analysis: All patients had blood samples collected for analysis of serum bone-specific alkaline phosphatase (BSAP).Bone-specific alkaline phosphatase (BSAP) is a useful marker of active bone formation. |
| Number of Participants With New/Worsening Morphometric Vertebral Fractures at Year 9 Compared to Year 6 | Year 6 (extension 2 baseline), Year 9 (3 years of study duration) | Morphometric 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 fracture was defined as an SQ reading that was greater than the baseline SQ reading. |
| Mean of Time to First Clinical Fracture | over 3 years of study duration | The mean of time to the first clinical fracture is estimated from the area under the Kaplan-Meier curve. |
| Change in Height at Years 7, 8 and 9 Relative to Year 6 | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | Height was measured using a stadiometer in millimeters (mm). A stadiometer is a piece of medical equipment used for measuring height. It is usually constructed out of a ruler and a sliding horizontal headpiece which is adjusted to rest on the top of the head. |
Countries
Argentina, Australia, Belgium, Canada, Colombia, Finland, France, Germany, Hong Kong, Hungary, Italy, New Zealand, Norway, Poland, Sweden, Switzerland, Thailand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Z9 (Zoledronic Acid 9) Group Z9 patients were those who had been treated with zoledronic acid for up to 9 years in the core (CZOL446H2301) and extension studies (CZOL446H2301E1 and CZOL446H2301E2). | 95 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) Group Z6P3 patients were those who had been treated with zoledronic acid for 6 years in the core (CZOL446H2301) and the first extension study (CZOL446H2301E1) followed by up to 3 years of placebo in the second extension study (CZOL446H2301E2). | 95 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Problems | 1 | 1 |
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Death | 1 | 5 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 15 | 10 |
Baseline characteristics
| Characteristic | Z9 (Zoledronic Acid 9) | Z6P3 (Zoledronic Acid 6 Placebo 3) | Total |
|---|---|---|---|
| Age, Continuous | 78 Years STANDARD_DEVIATION 4.71 | 78.1 Years STANDARD_DEVIATION 4.85 | 78.1 Years STANDARD_DEVIATION 4.77 |
| Sex: Female, Male Female | 95 Participants | 95 Participants | 190 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 62 / 92 | 58 / 95 |
| serious Total, serious adverse events | 24 / 92 | 28 / 95 |
Outcome results
Primary
Percentage Change in Total Hip Bone Mineral Density BMD at Year 6 (Baseline) and Year 9
Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 6 = 100\*(Year 9 - Year 6)/Year 6.
Time frame: Year 6 (baseline) and Year 9
Population: The modified intent-to-treat (MITT) population included all patients in the ITT population who had DXA measurements of the total hip at Visit 11 (Year 6) and Visit 15 (Year 9). This was the primary population for the primary efficacy parameter.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Percentage Change in Total Hip Bone Mineral Density BMD at Year 6 (Baseline) and Year 9 | -0.54 Percentage Change of BMD | Standard Error 0.433 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change in Total Hip Bone Mineral Density BMD at Year 6 (Baseline) and Year 9 | -1.31 Percentage Change of BMD | Standard Error 0.427 |
Secondary
Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9
Bone marker analysis: All patients had blood samples collected for analysis of serum bone-specific alkaline phosphatase (BSAP).Bone-specific alkaline phosphatase (BSAP) is a useful marker of active bone formation.
Time frame: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n = the number of patients with measurements at each visit as determined by the analysis window.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 8 (n=54, 57) | 7.84 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 7 (n=58, 65) | 8.4 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 9 (n=52, 56) | 8.46 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (n=59, 62) | 8.16 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 9 (n=52, 56) | 9.94 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 7 (n=58, 65) | 10.00 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 8 (n=54, 57) | 9.57 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (n=59, 62) | 8.95 ng/ml |
Secondary
Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9
Bone marker analysis: All patients had blood samples collected for analysis of serum c-terminal telopeptide of type I collagen (CTx). Serum CTX assays measure a fragment of the C-terminal telopeptide of type 1 collagen released during resorption of mature bone
Time frame: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n = the number of patients with measurements at each visit as determined by the analysis window.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (n=59, 58) | 0.19 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 7 (n=56, 51) | 0.2 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 8 (n=51, 52) | 0.22 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 9 (n=51,54) | 0.22 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 9 (n=51,54) | 0.22 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (n=59, 58) | 0.18 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 8 (n=51, 52) | 0.2 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 7 (n=56, 51) | 0.22 ng/ml |
Secondary
Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9
Bone marker analysis: All patients had blood samples collected for analysis of serum n-terminal propeptide of type I collagen (P1NP) The P1NP concentration is directly proportional to the amount of new collagen laid down during bone formation.
Time frame: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n = the number of patients with measurements at each visit as determined by the analysis window.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (n=88, 86) | 25.89 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 7 (n=58, 65) | 25.69 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 8 (n=54, 57) | 26.07 ng/ml |
| Z9 (Zoledronic Acid 9) | Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 9 (n=52,56) | 26.74 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 9 (n=52,56) | 27.41 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 6 (n=88, 86) | 24.98 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 8 (n=54, 57) | 25.19 ng/ml |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9 | Year 7 (n=58, 65) | 27.79 ng/ml |
Secondary
Change in Height at Years 7, 8 and 9 Relative to Year 6
Height was measured using a stadiometer in millimeters (mm). A stadiometer is a piece of medical equipment used for measuring height. It is usually constructed out of a ruler and a sliding horizontal headpiece which is adjusted to rest on the top of the head.
Time frame: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n = the number of patients with evaluable measurements at both Year 6 and the post-Year 6 visit, as determined by the analysis window.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Change in Height at Years 7, 8 and 9 Relative to Year 6 | Year 7 (n=58, 51) | -5.29 millimeters (mm) | Standard Error 1.171 |
| Z9 (Zoledronic Acid 9) | Change in Height at Years 7, 8 and 9 Relative to Year 6 | Year 8 (n=55, 49) | -10.16 millimeters (mm) | Standard Error 1.875 |
| Z9 (Zoledronic Acid 9) | Change in Height at Years 7, 8 and 9 Relative to Year 6 | Year 9 (n=52, 48) | -13.31 millimeters (mm) | Standard Error 1.975 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Change in Height at Years 7, 8 and 9 Relative to Year 6 | Year 7 (n=58, 51) | -4.84 millimeters (mm) | Standard Error 1.199 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Change in Height at Years 7, 8 and 9 Relative to Year 6 | Year 8 (n=55, 49) | -9.90 millimeters (mm) | Standard Error 2.006 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Change in Height at Years 7, 8 and 9 Relative to Year 6 | Year 9 (n=52, 48) | -11.65 millimeters (mm) | Standard Error 2.085 |
Secondary
Mean of Time to First Clinical Fracture
The mean of time to the first clinical fracture is estimated from the area under the Kaplan-Meier curve.
Time frame: over 3 years of study duration
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Mean of Time to First Clinical Fracture | 1212.05 Days | Standard Error 22.96 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Mean of Time to First Clinical Fracture | 1204.65 Days | Standard Error 26.35 |
Secondary
Number of Participants With New/Worsening Morphometric Vertebral Fractures at Year 9 Compared to Year 6
Morphometric 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 fracture was defined as an SQ reading that was greater than the baseline SQ reading.
Time frame: Year 6 (extension 2 baseline), Year 9 (3 years of study duration)
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n= the number of patients with the event
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Number of Participants With New/Worsening Morphometric Vertebral Fractures at Year 9 Compared to Year 6 | New Morphometric vertebral fracture | 3 participants |
| Z9 (Zoledronic Acid 9) | Number of Participants With New/Worsening Morphometric Vertebral Fractures at Year 9 Compared to Year 6 | New/worsening Morphometric vertebra | 3 participants |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Number of Participants With New/Worsening Morphometric Vertebral Fractures at Year 9 Compared to Year 6 | New Morphometric vertebral fracture | 5 participants |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Number of Participants With New/Worsening Morphometric Vertebral Fractures at Year 9 Compared to Year 6 | New/worsening Morphometric vertebra | 5 participants |
Secondary
Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0
Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 0 = 100\*(Year 9 - Year 0)/Year 0.
Time frame: Year 0 (core baseline), Year 7, Year 8, Year 9
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n = the number of patients with measurements at Year 0 and follow-up visits as determined by the analysis window.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 7 (n=83,75) | 5.11 percentage change of BMD | Standard Error 0.921 |
| Z9 (Zoledronic Acid 9) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 8 (n=72,71) | 6.12 percentage change of BMD | Standard Error 1.041 |
| Z9 (Zoledronic Acid 9) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 9 (n=67,68) | 4.16 percentage change of BMD | Standard Error 0.963 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 7 (n=83,75) | 3.86 percentage change of BMD | Standard Error 0.952 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 8 (n=72,71) | 4.43 percentage change of BMD | Standard Error 1.052 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 9 (n=67,68) | 3.88 percentage change of BMD | Standard Error 0.954 |
Secondary
Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6
Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 6 = 100\*(Year 9 - Year 6)/Year 6.
Time frame: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n = the number of patients with measurements at Year 6 and follow-up visits as determined by the analysis window.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6 | Year 7 (n=83,76) | -0.78 percentage change of BMD | Standard Error 0.433 |
| Z9 (Zoledronic Acid 9) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6 | Year 8 (n=73,72) | 0.00 percentage change of BMD | Standard Error 0.521 |
| Z9 (Zoledronic Acid 9) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6 | Year 9 (n=67,69) | -1.11 percentage change of BMD | Standard Error 0.554 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6 | Year 7 (n=83,76) | -1.24 percentage change of BMD | Standard Error 0.447 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6 | Year 8 (n=73,72) | -0.88 percentage change of BMD | Standard Error 0.528 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6 | Year 9 (n=67,69) | -1.17 percentage change of BMD | Standard Error 0.547 |
Secondary
Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0
Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 0 = 100\*(Year 9 - Year 0)/Year 0.
Time frame: Year 0 (core baseline), Year 7, Year 8, Year 9
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n = the number of patients with measurements at Year 0 and follow-up visits as determined by the analysis window.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 7 (n=83,75) | 4.81 percentage change of BMD | Standard Error 0.619 |
| Z9 (Zoledronic Acid 9) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 8 (n=72,71) | 5.35 percentage change of BMD | Standard Error 0.677 |
| Z9 (Zoledronic Acid 9) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 9 (n=67,68) | 4.64 percentage change of BMD | Standard Error 0.76 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 7 (n=83,75) | 3.73 percentage change of BMD | Standard Error 0.64 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 8 (n=72,71) | 3.65 percentage change of BMD | Standard Error 0.684 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0 | Year 9 (n=67,68) | 3.68 percentage change of BMD | Standard Error 0.752 |
Secondary
Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7 and 8 Compared to Year 6
Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 6 = 100\*(Year 9 - Year 6)/Year 6.
Time frame: Year 6 (extension 2 baseline), Year 7, Year 8
Population: The intent-to-treat (ITT) population included all patients who were enrolled in the extension study at Visit 12. This included patients who were randomized to Z9 and Z6P3 groups. n = the number of patients with measurements at Year 6 and follow-up visits as determined by the analysis window.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Z9 (Zoledronic Acid 9) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7 and 8 Compared to Year 6 | Year 7 (n=83,76) | -0.28 percentage change of BMD | Standard Error 0.336 |
| Z9 (Zoledronic Acid 9) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7 and 8 Compared to Year 6 | Year 8 (n=73,72) | -0.14 percentage change of BMD | Standard Error 0.311 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7 and 8 Compared to Year 6 | Year 7 (n=83,76) | -0.83 percentage change of BMD | Standard Error 0.347 |
| Z6P3 (Zoledronic Acid 6 Placebo 3) | Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7 and 8 Compared to Year 6 | Year 8 (n=73,72) | -1.06 percentage change of BMD | Standard Error 0.315 |