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
2 other identifiers
interventional
643
7 countries
45
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Nov 2012
Typical duration for phase_4
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 7, 2012
CompletedFirst Submitted
Initial submission to the registry
November 20, 2012
CompletedFirst Posted
Study publicly available on registry
November 26, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 7, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
January 7, 2015
CompletedResults Posted
Study results publicly available
January 25, 2016
CompletedMarch 10, 2020
March 1, 2020
2.2 years
November 20, 2012
December 9, 2015
March 2, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis
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.
Baseline and Month 12
Secondary Outcomes (3)
Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis
Baseline and Month 12
Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis
Baseline and Month 12
Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
Baseline and Month 12
Study Arms (2)
Denosumab 60 mg
EXPERIMENTALParticipants received denosumab 60 mg subcutaneous injection once every 6 months for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
Zoledronic Acid 5 mg
ACTIVE COMPARATORParticipants 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
Denosumab 60 mg administered by subcutaneous injection once every 6 months.
Zoledronic acid 5 mg administered by intravenous infusion once a year
Administered by subcutaneous injection once every 6 months
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (45)
Research Site
Santa Monica, California, 90404, United States
Research Site
Lakewood, Colorado, 80227, United States
Research Site
Longmont, Colorado, 80501, United States
Research Site
Washington D.C., District of Columbia, 20007, United States
Research Site
Bethesda, Maryland, 20817, United States
Research Site
Hagerstown, Maryland, 21740, United States
Research Site
Detroit, Michigan, 48236, United States
Research Site
West Haverstraw, New York, 10993, United States
Research Site
Houston, Texas, 77074, United States
Research Site
Maroubra, New South Wales, 2035, Australia
Research Site
Penrith, New South Wales, 2750, Australia
Research Site
St Leonards, New South Wales, 2065, Australia
Research Site
Box Hill, Victoria, 3128, Australia
Research Site
Geelong, Victoria, 3220, Australia
Research Site
Parkville, Victoria, 3050, Australia
Research Site
Brussels, 1000, Belgium
Research Site
Brussels, 1020, Belgium
Research Site
Brussels, 1050, Belgium
Research Site
Brussels, 1090, Belgium
Research Site
Genk, 3600, Belgium
Research Site
Leuven, 3000, Belgium
Research Site
Liège, 4020, Belgium
Research Site
Merksem, 2170, Belgium
Research Site
Tessenderlo, 3980, Belgium
Research Site
Wilrijk, 2610, Belgium
Research Site
Yvoir, 5530, Belgium
Research Site
Calgary, Alberta, T2N 4Z6, Canada
Research Site
Vancouver, British Columbia, V5Z 4E1, Canada
Research Site
Halifax, Nova Scotia, B3H 2Y9, Canada
Research Site
Toronto, Ontario, M5C 2T2, Canada
Research Site
Toronto, Ontario, M5G 2C4, Canada
Research Site
Toronto, Ontario, M9W 4L6, Canada
Research Site
Québec, Quebec, G1V 3M7, Canada
Research Site
Aalborg, 9000, Denmark
Research Site
Ballerup Municipality, 2750, Denmark
Research Site
Vejle, 7100, Denmark
Research Site
Bialystok, 15-879, Poland
Research Site
Krakow, 31-501, Poland
Research Site
Torun, 87-100, Poland
Research Site
Warsaw, 01-192, Poland
Research Site
Granada, Andalusia, 18012, Spain
Research Site
Barcelona, Catalonia, 08036, Spain
Research Site
Barcelona, Catalonia, 08041, Spain
Research Site
Madrid, 28009, Spain
Research Site
Madrid, 28040, Spain
Related Publications (3)
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.
PMID: 27270237BACKGROUNDMiller 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.
PMID: 31776637BACKGROUNDChotiyarnwong 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.
PMID: 31999376BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Amgen Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 20, 2012
First Posted
November 26, 2012
Study Start
November 7, 2012
Primary Completion
January 7, 2015
Study Completion
January 7, 2015
Last Updated
March 10, 2020
Results First Posted
January 25, 2016
Record last verified: 2020-03