3 yr Efficacy & Safety Study of Zoledronic Acid in Post-menopausal Women With Osteoporosis Treated With Zol Acid for 6 Yrs

Study Overview
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Brief Summary
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This second extension will evaluate the efficacy and long term safety of zoledronic acid in women with post-menopausal osteoporosis

Official Title
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A 3-year, Multicenter, Double-blind, Randomized, Placebo-controlled Extension to CZOL446H2301E1 to Evaluate the Efficacy and Long Term Safety of 6 and 9 Years Zoledronic Acid Treatment of Postmenopausal Women With Osteoporosis

Conditions
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Post-menopausal Osteoporosis

Intervention / Treatment
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* Drug: Placebo
* Drug: Zoledronic acid


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching placebo administered intravenously. | Drug: Placebo<br> <br> |
| Experimental: Zoledronic acid<br> | Drug: Zoledronic acid<br> <br> * Other names: Reclast®, Aclasta®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Year 6 (baseline) and Year 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Year 6 (extension 2 baseline), Year 7, Year 8 | 
| 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. | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | 
| 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. | Year 0 (core baseline), Year 7, Year 8, Year 9 | 
| 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. | Year 0 (core baseline), Year 7, Year 8, Year 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 | 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 | Year 6 (extension 2 baseline), Year 7, Year 8, Year 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 | 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. | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | 
| 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. | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | 
| 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. | Year 6 (extension 2 baseline), Year 9 (3 years of study duration) | 
| 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. | over 3 years of study duration | 
| 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. | Year 6 (extension 2 baseline), Year 7, Year 8, Year 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, zoledronic acid, post-menopausal