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

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

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.

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