Back to resultsSafety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis
Primary Purpose
Post Menopausal Osteoporosis
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Denosumab
Zoledronic Acid
Placebo to Denosumab
Placebo to Zoledronic Acid
Sponsored by
About this trial
This is an interventional treatment trial for Post Menopausal Osteoporosis
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
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Denosumab 60 mg
Zoledronic Acid 5 mg
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis
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
Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01732770
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
November 7, 2012 (Actual)
Primary Completion Date
January 7, 2015 (Actual)
Study Completion Date
January 7, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Menopausal Osteoporosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
643 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Denosumab 60 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Zoledronic Acid 5 mg
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Denosumab
Other Intervention Name(s)
Prolia®, AMG 162
Intervention Description
Denosumab 60 mg administered by subcutaneous injection once every 6 months.
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid
Other Intervention Name(s)
Reclast, Aclasta
Intervention Description
Zoledronic acid 5 mg administered by intravenous infusion once a year
Intervention Type
Drug
Intervention Name(s)
Placebo to Denosumab
Intervention Description
Administered by subcutaneous injection once every 6 months
Intervention Type
Drug
Intervention Name(s)
Placebo to Zoledronic Acid
Intervention Description
Administered by intravenous infusion once a year
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis
Description
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.
Time Frame
Baseline and Month 12
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis
Description
BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility.
Time Frame
Baseline and Month 12
Title
Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis
Time Frame
Baseline and Month 12
Title
Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
Time Frame
Baseline and Month 12
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Research Site
City
Lakewood
State/Province
Colorado
ZIP/Postal Code
80227
Country
United States
Facility Name
Research Site
City
Longmont
State/Province
Colorado
ZIP/Postal Code
80501
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Research Site
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Research Site
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
Facility Name
Research Site
City
West Haverstraw
State/Province
New York
ZIP/Postal Code
10993
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
Research Site
City
Maroubra
State/Province
New South Wales
ZIP/Postal Code
2035
Country
Australia
Facility Name
Research Site
City
Penrith
State/Province
New South Wales
ZIP/Postal Code
2750
Country
Australia
Facility Name
Research Site
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Research Site
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
Research Site
City
Geelong
State/Province
Victoria
ZIP/Postal Code
3220
Country
Australia
Facility Name
Research Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Research Site
City
Brussels
ZIP/Postal Code
1050
Country
Belgium
Facility Name
Research Site
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Research Site
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Research Site
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Research Site
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Facility Name
Research Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Research Site
City
Liège
ZIP/Postal Code
4020
Country
Belgium
Facility Name
Research Site
City
Merksem
ZIP/Postal Code
2170
Country
Belgium
Facility Name
Research Site
City
Tessenderlo
ZIP/Postal Code
3980
Country
Belgium
Facility Name
Research Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Research Site
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Research Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
Research Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E1
Country
Canada
Facility Name
Research Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5C 2T2
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M9W 4L6
Country
Canada
Facility Name
Research Site
City
Quebec
ZIP/Postal Code
G1V 3M7
Country
Canada
Facility Name
Research Site
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Research Site
City
Ballerup
ZIP/Postal Code
2750
Country
Denmark
Facility Name
Research Site
City
Vejle
ZIP/Postal Code
7100
Country
Denmark
Facility Name
Research Site
City
Bialystok
ZIP/Postal Code
15-879
Country
Poland
Facility Name
Research Site
City
Kraków
ZIP/Postal Code
31-501
Country
Poland
Facility Name
Research Site
City
Torun
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
01-192
Country
Poland
Facility Name
Research Site
City
Granada
State/Province
Andalucía
ZIP/Postal Code
18012
Country
Spain
Facility Name
Research Site
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08036
Country
Spain
Facility Name
Research Site
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08041
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
27270237
Citation
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.
Results Reference
background
PubMed Identifier
31776637
Citation
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.
Results Reference
background
PubMed Identifier
31999376
Citation
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.
Results Reference
background
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis
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