Post Menopausal OsteoporosisPhase 4NCT01732770
Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis
A Phase 4 study testing Denosumab and Zoledronic Acid in people with Post Menopausal Osteoporosis, run by Amgen at 45 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 years and older, women only
- Conditions the study is for
- Post Menopausal Osteoporosis
- What is being tested?
- Denosumab and Zoledronic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 643 participants
- Where
- 45 sitesin 7 countries
- Study dates
- 7 Nov 2012to 7 Jan 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
45 sites in 7 countries.
45 sites in 7 countries
Belgium11 sites
Research Site
Brussels, 1000
Research Site
Brussels, 1020
Research Site
Brussels, 1050
Research Site
Brussels, 1090
Research Site
Genk, 3600
Research Site
Leuven, 3000
Research Site
Liège, 4020
Research Site
Merksem, 2170
Research Site
Tessenderlo, 3980
Research Site
Wilrijk, 2610
Research Site
Yvoir, 5530
United States9 sites
Research Site
Bethesda, Maryland, 20817
Research Site
Detroit, Michigan, 48236
Research Site
Hagerstown, Maryland, 21740
Research Site
Houston, Texas, 77074
Research Site
Lakewood, Colorado, 80227
Research Site
Longmont, Colorado, 80501
Research Site
Santa Monica, California, 90404
Research Site
Washington D.C., District of Columbia, 20007
Research Site
West Haverstraw, New York, 10993
Canada7 sites
Research Site
Calgary, Alberta, T2N 4Z6
Research Site
Halifax, Nova Scotia, B3H 2Y9
Research Site
Québec, Quebec, G1V 3M7
Research Site
Toronto, Ontario, M5C 2T2
Research Site
Toronto, Ontario, M5G 2C4
Research Site
Toronto, Ontario, M9W 4L6
Research Site
Vancouver, British Columbia, V5Z 4E1
Australia6 sites
Research Site
Box Hill, Victoria, 3128
Research Site
Geelong, Victoria, 3220
Research Site
Maroubra, New South Wales, 2035
Research Site
Parkville, Victoria, 3050
Research Site
Penrith, New South Wales, 2750
Research Site
St Leonards, New South Wales, 2065
Spain5 sites
Research Site
Barcelona, Catalonia, 08036
Research Site
Barcelona, Catalonia, 08041
Research Site
Granada, Andalusia, 18012
Research Site
Madrid, 28009
Research Site
Madrid, 28040
Poland4 sites
Research Site
Bialystok, 15-879
Research Site
Krakow, 31-501
Research Site
Torun, 87-100
Research Site
Warsaw, 01-192
Denmark3 sites
Research Site
Aalborg, 9000
Research Site
Ballerup Municipality, 2750
Research Site
Vejle, 7100
About this study
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
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.
- Conditions
- Post Menopausal Osteoporosis
- Being tested
- Denosumab, Zoledronic Acid, Placebo to Denosumab, Placebo to Zoledronic Acid
- Medical subject headings
- Osteoporosis, Postmenopausal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabBiological
Also called Prolia®, AMG 162
Denosumab 60 mg administered by subcutaneous injection once every 6 months.
Zoledronic AcidDrug
Also called Reclast, Aclasta
Zoledronic acid 5 mg administered by intravenous infusion once a year
Placebo to DenosumabDrug
Administered by subcutaneous injection once every 6 months
Placebo to Zoledronic AcidDrug
Administered by intravenous infusion once a year
| Study group | Role | What they receive |
|---|---|---|
| Denosumab 60 mg | Experimental | 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. Receives: Biological: Denosumab; Drug: Placebo to Zoledronic Acid |
| Zoledronic Acid 5 mg | Active comparator | 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. Receives: Drug: Zoledronic Acid; Drug: Placebo to Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Month 12
Secondary outcomes (3)
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.
Measured: Baseline and Month 12
Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis
Measured: Baseline and Month 12
Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
Measured: Baseline and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2012 (estimated)
- Study start7 Nov 2012
- Primary completion7 Jan 2015
- Study completion7 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Post Menopausal OsteoporosisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 643 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01732770
- Sponsor's protocol ID
- 20110153
- Other IDs
- 2012-001821-28
- Status last verified
- Mar 2020
- First submitted
- 20 Nov 2012
- Last updated
- 10 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 27270237Miller 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.
PubMed 31776637Chotiyarnwong 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.
PubMed 31999376
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01732770
- Acronym / sponsor ID
- 20110153
- Conditions
- Post Menopausal Osteoporosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 643 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 7 Nov 2012 (actual)
- Primary completion
- 7 Jan 2015 (actual)
- Study completion
- 7 Jan 2015 (actual)
- First posted
- 26 Nov 2012 (estimated)
- Results
- Posted 25 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab 60 mg | Experimental | Biological: Denosumab, Drug: Placebo to Zoledronic AcidParticipants 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 comparator | Drug: Zoledronic Acid, Drug: Placebo to DenosumabParticipants 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. |
Who may qualify
- Ages
- 55 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (19 listed)
- Received other osteoporosis treatment or bone active treatment
- Evidence of history of any of the following:
- Abnormalities of the following per central laboratory reference ranges:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: Prolia®, AMG 162Denosumab 60 mg administered by subcutaneous injection once every 6 months. | Biological | Denosumab 60 mg |
| Zoledronic AcidAlso: Reclast, AclastaZoledronic acid 5 mg administered by intravenous infusion once a year | Drug | Zoledronic Acid 5 mg |
| Placebo to DenosumabAdministered by subcutaneous injection once every 6 months | Drug | Zoledronic Acid 5 mg |
| Placebo to Zoledronic AcidAdministered by intravenous infusion once a year | Drug | Denosumab 60 mg |
Primary outcome
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.
3 secondary outcomes
Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis
Time frame: Baseline and Month 12
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27270237Miller 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.
- Background: PubMed 31776637Miller 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.
- Background: PubMed 31999376Chotiyarnwong 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
45 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Denosumab and Zoledronic Acid in people with Post Menopausal Osteoporosis, run by Amgen at 45 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in Belgium, United States, Canada, Australia, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis (time frame: Baseline and Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01732770, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2020.