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

NCT ID: NCT01732770

Last Updated: 2020-03-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

643 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-07

Study Completion Date

2015-01-07

Brief Summary

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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

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Conditions

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Post Menopausal Osteoporosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Denosumab

Intervention Type BIOLOGICAL

Denosumab 60 mg administered by subcutaneous injection once every 6 months.

Placebo to Zoledronic Acid

Intervention Type DRUG

Administered by intravenous infusion once a year

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.

Group Type ACTIVE_COMPARATOR

Zoledronic Acid

Intervention Type DRUG

Zoledronic acid 5 mg administered by intravenous infusion once a year

Placebo to Denosumab

Intervention Type DRUG

Administered by subcutaneous injection once every 6 months

Interventions

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Denosumab

Denosumab 60 mg administered by subcutaneous injection once every 6 months.

Intervention Type BIOLOGICAL

Zoledronic Acid

Zoledronic acid 5 mg administered by intravenous infusion once a year

Intervention Type DRUG

Placebo to Denosumab

Administered by subcutaneous injection once every 6 months

Intervention Type DRUG

Placebo to Zoledronic Acid

Administered by intravenous infusion once a year

Intervention Type DRUG

Other Intervention Names

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Prolia® AMG 162 Reclast Aclasta

Eligibility Criteria

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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
Minimum Eligible Age

55 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Santa Monica, California, United States

Site Status

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Lakewood, Colorado, United States

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Longmont, Colorado, United States

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Washington D.C., District of Columbia, United States

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Bethesda, Maryland, United States

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Hagerstown, Maryland, United States

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Detroit, Michigan, United States

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West Haverstraw, New York, United States

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Houston, Texas, United States

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Maroubra, New South Wales, Australia

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Penrith, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Box Hill, Victoria, Australia

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Geelong, Victoria, Australia

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Parkville, Victoria, Australia

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Brussels, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Genk, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Merksem, , Belgium

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Tessenderlo, , Belgium

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Wilrijk, , Belgium

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Yvoir, , Belgium

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Calgary, Alberta, Canada

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Vancouver, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Québec, Quebec, Canada

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Aalborg, , Denmark

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Ballerup Municipality, , Denmark

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Vejle, , Denmark

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Bialystok, , Poland

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Krakow, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Granada, Andalusia, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Madrid, , Spain

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Madrid, , Spain

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Countries

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United States Australia Belgium Canada Denmark Poland Spain

References

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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.

Reference Type BACKGROUND
PMID: 27270237 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31776637 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31999376 (View on PubMed)

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2012-001821-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20110153

Identifier Type: -

Identifier Source: org_study_id

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