Double-blind Extension of HORIZON Pivotal Fracture Trial (Zoledronic Acid in the Treatment of Postmenopausal Osteoporosis)

Study Overview
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Brief Summary
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This extension study is designed to assess the long term safety and efficacy of zoledronic acid in postmenopausal women with osteoporosis who have participated in the CZOL446H2301 (NCT00049829): HORIZON Pivotal Fracture Trial. This extension study began after the 3-year core study ended. Baseline is the same as Year 3.

Official Title
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A 3-year, Double-blind Extension to CZOL446H2301 to Evaluate the Long-term Safety and Efficacy of Zoledronic Acid in the Treatment of Osteoporosis in Postmenopausal Women Taking Calcium and Vitamin D

Conditions
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Osteoporosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have received 3 infusions in the HORIZON-Pivotal Fracture (PFT) Study. Exclusion Criteria: Poor kidney, eye, or liver health Use of certain therapies for osteoporosis in the HORIZON-PFT study (other than the study medication) Abnormal calcium levels in the blood Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 68 Years
Maximum Age: 90 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 |
| --- | --- |
| Experimental: Zoledronic Acid 6<br>Patients who received Zoledronic acid for 3 years in the core study (CZOL446H2301; NCT00049829) received a single intravenous infusion of 5 mg Zoledronic acid once a year for 3 years (at Months 36, 48 and 60) in this extension study for a total of 6 years of treatment. | Drug: Zoledronic Acid<br>* Zoledronic Acid 5 mg in 100 mL physiologic 0.9% normal saline for intravenous infusion.<br>* Other names: Reclast, Aclasta;|
| Placebo Comparator: Zoledronic Acid 3 Placebo 3<br>Patients who were treated with Zoledronic acid for 3 years in the core study received a single intravenous matching Placebo infusion once a year for 3 years in this extension study. | Drug: Placebo<br>* 100 mL physiologic 0.9% normal saline for intravenous infusion.<br>* Other names: Reclast, Aclasta;|
| Experimental: Placebo 3 Zoledronic Acid 3<br>Patients who were treated with placebo for 3 years in the core study received 5 mg Zoledronic acid in a single intravenous infusion once a year for 3 years (at Months 36, 48 and 60) in this extension study. | Drug: Zoledronic Acid<br>* Zoledronic Acid 5 mg in 100 mL physiologic 0.9% normal saline for intravenous infusion.<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 Bone Mineral Density (BMD) of Femoral Neck at Year 6 Relative to Year 3 | The primary efficacy variable was the percentage change in BMD of the femoral neck as measured by dual x-ray absorptiometry (DXA) at Year 6 relative to Year 3. It was derived as 100 *(femoral neck BMD at Year 6 - femoral neck BMD at Year 3) / (femoral neck BMD at Year 3). | Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72; end of extension study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Resorption and Formation Biochemical Markers at Year 4.5: P1NP | The amount of serum n-terminal propeptide of type I collagen (P1NP) as determined by the central laboratory. | Year 4.5 | 
| Bone Resorption and Formation Biochemical Markers at Year 6: P1NP | The amount of serum P1NP as determined by the central laboratory | Year 6 | 
| Percentage Change in BMD of Lumbar Spine at Year 4.5 Relative to Year 3 | The percentage change in BMD as measured by DXA at Year 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3). | Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) | 
| Percentage Change in BMD of Lumbar Spine at Year 6 Relative to Year 3 | The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3). | Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 | 
| Percentage Change in BMD of Distal Radius at Year 4.5 Relative to Year 3 | The percentage change in BMD as measured by DXA at Year 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3). | Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) | 
| Percentage Change in BMD of Distal Radius at Year 6 Relative to Year 3 | The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3). | Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72) | 
| Percentage Change in BMD of Femoral Neck, Total Hip and Trochanter at Year 4.5 Relative to Year 3 | The percentage change in BMD as measured by DXA at 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3). | Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54) | 
| Percentage Change in BMD of Femoral Neck, Total Hip and Trochanter at Year 6 Relative to Year 3 | The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3). | Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72) | 
| Percentage of Patients With New and New/Worsening Morphometric Vertebral Fractures | Lateral vertebral x-rays were performed at the final core study visit and at Year 6 and read by a central expert reader at a central imaging laboratory to assess for new or new/worsening morphometric vertebral fracture. The percentage of patients with new morphometric vertebral fractures (observed for the first time) and patients with either new or worsening morphometric vertebral fractures was calculated. | Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 | 
| Number of Participants With Incidence of Clinical Fracture | Clinical fracture excludes finger, toe, and facial bone fractures. Clinical vertebral fracture includes thoracic spine fracture and lumbar spine fracture. Non-vertebral fracture excludes clinical vertebral, finger, toe, and facial bone fractures. | Extension Baseline (Year 3; Month 36) to Year 6 | 
| Qualitative Bone Biopsy Parameters | Unpaired transiliac crest bone biopsy was performed for histomorphometry, which was obtained after double tetracycline labeling. No data were collected for Patients who received Placebo for the first 3 years of the study (Placebo 3 Zoledronic Acid 3). | End of Study Visit at Year 6 | 
| Change in Serum Creatinine From Baseline to 9-11 Days Post Year 3 Infusion | Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after study drug infusion in Z6 patients compared to Z3P3 patients and in P3Z3 patients. | Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 3 infusion | 
| Change in Serum Creatinine From Baseline to 9-11 Days Post Year 4 Infusion | Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after Year 4 study drug infusion. | Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 4 infusion | 
| Change in Serum Creatinine From Baseline to 9-11 Days Post Year 5 Infusion | Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after Year 5 study drug infusion. | Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 5 infusion | 
| The Number of Participants With Clinically Significant Laboratory Parameters | Evaluate the laboratory key profile such as Calcium, Creatinine and Urea. The number of patients with clinically significant calcium, creatinine and urea were reported. | Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to Year 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Zoledronic Acid