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

• ClinicalTrials.gov Identifier: NCT01732770
• Recruitment Status: Completed
• First Posted: November 26, 2012
• Results First Posted: January 25, 2016
• Last Update Posted: March 10, 2020
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: November 20, 2012
• First Posted Date: November 26, 2012
• Results First Submitted Date: December 9, 2015
• Results First Posted Date: January 25, 2016
• Last Update Posted Date: March 10, 2020
• Actual Study Start Date: November 7, 2012
• Actual Primary Completion Date: January 7, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 17, 2015)

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.

Original Primary Outcome Measures (submitted: November 20, 2012)

Bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA) of lumbar spine at 12 months [ Time Frame: 12 Months ]

The primary objective of this study is to evaluate if the effect of administering Denosumab (60 mg subcutaneously [SC] every 6 months [Q6M]) is not inferior to that of Zoledronic Acid (5 mg intravenously [IV] once yearly) in postmenopausal women with osteoporosis previously treated with oral bisphosphonates with respect to change in bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA) of lumbar spine at 12 months

Current Secondary Outcome Measures (submitted: December 17, 2015)

• 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 ]

Original Secondary Outcome Measures (submitted: November 20, 2012)

BMD by DXA of total hip at 12 months (non-inferiority); BMD by DXA of lumbar spine at 12 months (superiority); BMD by DXA of total hip at 12 months (superiority) [ Time Frame: 12 Months ]

Secondary Objective(s): Compare the efficacy of administering Denosumab (60 mg SC Q6M) with that of Zoledronic Acid (5 mg IV once yearly) on the following: BMD by DXA of total hip at 12 months (non-inferiority); BMD by DXA of lumbar spine at 12 months (superiority); BMD by DXA of total hip at 12 months (superiority)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis
• 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Post Menopausal Osteoporosis

Intervention

• Biological: Denosumab
  Denosumab 60 mg administered by subcutaneous injection once every 6 months.
  Other Names:

  • Prolia®
  • AMG 162
• 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
• Drug: Placebo to Zoledronic Acid
  Administered by intravenous infusion once a year

Study Arms

• 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.
  Interventions:

  • Biological: Denosumab
  • Drug: Placebo to Zoledronic Acid
• 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.
  Interventions:

  • Drug: Zoledronic Acid
  • Drug: Placebo to Denosumab

Publications *

• 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, Czerwiński 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2014): 643
• Original Estimated Enrollment (submitted: November 20, 2012): 620
• Actual Study Completion Date: January 7, 2015
• Actual Primary Completion Date: January 7, 2015 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Denmark, Poland, Spain, United States

Administrative Information

• NCT Number: NCT01732770
• Other Study ID Numbers: 20110153; 2012-001821-28 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Amgen
• Study Sponsor: Amgen
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: March 2020