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

Post Menopausal Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01732770
• Other study ID #: 20110153
• Secondary ID: 2012-001821-28
• Status: Completed
• Phase: Phase 4
• Start date: November 7, 2012
• Est. completion date: January 7, 2015

Study information

• Verified date: March 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 643
• Est. completion date: January 7, 2015
• Est. primary completion date: January 7, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Post Menopausal Osteoporosis

Intervention

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

Drug:
• Zoledronic Acid
Zoledronic acid 5 mg administered by intravenous infusion once a year
• Placebo to Denosumab
Administered by subcutaneous injection once every 6 months
• Placebo to Zoledronic Acid
Administered by intravenous infusion once a year

Locations

Country	Name	City	State
Australia	Research Site	Box Hill	Victoria
Australia	Research Site	Geelong	Victoria
Australia	Research Site	Maroubra	New South Wales
Australia	Research Site	Parkville	Victoria
Australia	Research Site	Penrith	New South Wales
Australia	Research Site	St Leonards	New South Wales
Belgium	Research Site	Brussel
Belgium	Research Site	Brussels
Belgium	Research Site	Bruxelles
Belgium	Research Site	Bruxelles
Belgium	Research Site	Genk
Belgium	Research Site	Leuven
Belgium	Research Site	Liège
Belgium	Research Site	Merksem
Belgium	Research Site	Tessenderlo
Belgium	Research Site	Wilrijk
Belgium	Research Site	Yvoir
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Denmark	Research Site	Aalborg
Denmark	Research Site	Ballerup
Denmark	Research Site	Vejle
Poland	Research Site	Bialystok
Poland	Research Site	Kraków
Poland	Research Site	Torun
Poland	Research Site	Warszawa
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Barcelona	Cataluña
Spain	Research Site	Granada	Andalucía
Spain	Research Site	Madrid
Spain	Research Site	Madrid
United States	Research Site	Bethesda	Maryland
United States	Research Site	Detroit	Michigan
United States	Research Site	Hagerstown	Maryland
United States	Research Site	Houston	Texas
United States	Research Site	Lakewood	Colorado
United States	Research Site	Longmont	Colorado
United States	Research Site	Santa Monica	California
United States	Research Site	Washington	District of Columbia
United States	Research Site	West Haverstraw	New York

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  Poland,  Spain, 

References & Publications (3)

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 Jan 30. doi: 10.1002/jbmr.3972. [Epub ahead of print] — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline and Month 12
Secondary	Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis		Baseline and Month 12
Secondary	Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis		Baseline and Month 12

External Links

•   AmgenTrials clinical trials website