Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis

Study Overview
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Brief Summary
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This study will compare the effectiveness of denosumab treatment every 6 months with once yearly zoledronic acid treatment on bone mineral density (BMD) at various skeletal sites.

Official Title
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A Randomized Double-blind Study to Evaluate the Safety and Efficacy of Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

Conditions
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Post Menopausal Osteoporosis

Intervention / Treatment
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* Biological: Denosumab
* Drug: Zoledronic Acid
* Drug: Placebo to Denosumab
* Drug: Placebo to Zoledronic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory postmenopausal women. Age 55 years or older Subject has provided informed consent prior to any study specific procedures Received oral bisphosphonate therapy for osteoporosis at least 2 years prior to screening visit Screening BMD (g/cm²) values at the lumbar spine, total hip or femoral neck values of equal to or less than those listed in the protocol. At least 2 lumbar vertebrae and one hip must be evaluable by dual energy x-ray absorptiometry (DXA) at the screening visit Exclusion Criteria: Received other osteoporosis treatment or bone active treatment Evidence of history of any of the following: hyperthyroidism (stable on antithyroid therapy is allowed) hypothyroidism (stable on thyroid replacement therapy is allowed) hypo- or hyperparathyroidism hypo- or hypercalcemia based on the central laboratory reference ranges Recent tooth extraction (within 6 months of screening visit) Paget disease of bone (subject report or chart review) other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis imperfecta) (chart review) Abnormalities of the following per central laboratory reference ranges: vitamin D deficiency (25[OH] vitamin D level < 20 ng/mL), repletion will be allowed and subjects may be re-screened hypercalcemia elevated transaminases ≥ 2.0 x upper limits of normal (ULN) History of any solid organ or bone marrow transplant Malignancy (except nonmelanoma skin cancers, cervical or breast ductal carcinoma in situ) within the last 5 years Known intolerance to calcium or vitamin D supplements Self-reported alcohol or drug abuse within 12 months prior to screening Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s) History or evidence of any other clinically significant disorder, condition or disease that in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

Ages Eligible for Study
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Minimum Age: 55 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab 60 mg<br>Participants received denosumab 60 mg subcutaneous injection once every 6 months for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1. | Biological: Denosumab<br>* Denosumab 60 mg administered by subcutaneous injection once every 6 months.<br>* Other names: AMG 162;Drug: Placebo to Zoledronic Acid<br>* Administered by intravenous infusion once a year<br>|
| Active Comparator: Zoledronic Acid 5 mg<br>Participants received zoledronic acid 5 mg by intravenous infusion on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6. | Drug: Zoledronic Acid<br>* Zoledronic acid 5 mg administered by intravenous infusion once a year<br>* Other names: Aclasta;Drug: Placebo to Denosumab<br>* Administered by subcutaneous injection once every 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis | Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility. | Baseline and Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis | BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility. | Baseline and Month 12 | 
| Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis |  | Baseline and Month 12 | 
| Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis |  | Baseline and Month 12 |