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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: January 7, 2015

Interventions

  • Biological: Denosumab
    • Denosumab 60 mg administered by subcutaneous injection once every 6 months.
  • Drug: Zoledronic Acid
    • Zoledronic acid 5 mg administered by intravenous infusion once a year
  • Drug: Placebo to Denosumab
    • Administered by subcutaneous injection once every 6 months
  • Drug: Placebo to Zoledronic Acid
    • Administered by intravenous infusion once a year

Arms, Groups and Cohorts

  • Experimental: Denosumab 60 mg
    • 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.
  • Active Comparator: Zoledronic Acid 5 mg
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 – Non-inferiority Analysis
    • Time Frame: Baseline and Month 12
    • 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.

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 55 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Amgen
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • MD, Study Director, Amgen

References

Miller PD, Pannacciulli N, Brown JP, Czerwinski E, Nedergaard BS, Bolognese MA, Malouf J, Bone HG, Reginster JY, Singer A, Wang C, Wagman RB, Cummings SR. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. J Clin Endocrinol Metab. 2016 Aug;101(8):3163-70. doi: 10.1210/jc.2016-1801. Epub 2016 Jun 6.

Miller PD, Pannacciulli N, Malouf-Sierra J, Singer A, Czerwinski E, Bone HG, Wang C, Huang S, Chines A, Lems W, Brown JP. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int. 2020 Jan;31(1):181-191. doi: 10.1007/s00198-019-05233-x. Epub 2019 Nov 28.

Chotiyarnwong P, McCloskey E, Eastell R, McClung MR, Gielen E, Gostage J, McDermott M, Chines A, Huang S, Cummings SR. A Pooled Analysis of Fall Incidence From Placebo-Controlled Trials of Denosumab. J Bone Miner Res. 2020 Jun;35(6):1014-1021. doi: 10.1002/jbmr.3972. Epub 2020 Apr 2.

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