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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01732770
First received: November 20, 2012
Last updated: January 28, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Post Menopausal Osteoporosis
Biological: Denosumab
Drug: Zoledronic Acid
Drug: Placebo to Denosumab
Drug: Placebo to Zoledronic Acid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]

Enrollment: 643
Study Start Date: November 2012
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: Denosumab
Denosumab 60 mg administered by subcutaneous injection once every 6 months.
Other Names:
  • Prolia®
  • AMG 162
Drug: Placebo to Zoledronic Acid
Administered by intravenous infusion once a year
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.
Drug: Zoledronic Acid
Zoledronic acid 5 mg administered by intravenous infusion once a year
Other Names:
  • Reclast
  • Aclasta
Drug: Placebo to Denosumab
Administered by subcutaneous injection once every 6 months

  Eligibility

Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01732770

  Show 45 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01732770     History of Changes
Other Study ID Numbers: 20110153  2012-001821-28 
Study First Received: November 20, 2012
Results First Received: December 9, 2015
Last Updated: January 28, 2016
Health Authority: United States: Food and Drug Administration
Germany: Federal Office for Radiation Protection
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Germany: Paul-Ehrlich-Institut
Denmark: Danish Health and Medicines Authority
Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016