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

Amgen

Status and phase: Completed; Phase 4

Conditions: Post Menopausal Osteoporosis

Treatments: Drug: Zoledronic Acid; Drug: Placebo to Zoledronic Acid; Drug: Placebo to Denosumab; Biological: Denosumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01732770

2012-001821-28 (EudraCT Number)

20110153

Details and patient eligibility

About

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.

Enrollment: 643 patients

Sex: Female

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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643 participants in 2 patient groups

Denosumab 60 mg

Experimental group

Description:

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.

Treatment:

Biological: Denosumab

Drug: Placebo to Zoledronic Acid

Zoledronic Acid 5 mg

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to Denosumab

Drug: Zoledronic Acid