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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01732770




Registration number
NCT01732770
Ethics application status
Date submitted
20/11/2012
Date registered
26/11/2012
Date last updated
10/03/2020

Titles & IDs
Public title
Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis
Scientific 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
Secondary ID [1] 0 0
2012-001821-28
Secondary ID [2] 0 0
20110153
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post Menopausal Osteoporosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoporosis
Reproductive Health and Childbirth 0 0 0 0
Menstruation and menopause

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Denosumab
Treatment: Drugs - Zoledronic Acid
Treatment: Drugs - Placebo to Denosumab
Treatment: Drugs - Placebo to Zoledronic Acid

Experimental: 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.

Active Comparator: 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.


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

Treatment: Drugs: Zoledronic Acid
Zoledronic acid 5 mg administered by intravenous infusion once a year

Treatment: Drugs: Placebo to Denosumab
Administered by subcutaneous injection once every 6 months

Treatment: Drugs: Placebo to Zoledronic Acid
Administered by intravenous infusion once a year
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis
Timepoint [1] 0 0
Baseline and Month 12
Secondary outcome [1] 0 0
Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis
Timepoint [1] 0 0
Baseline and Month 12
Secondary outcome [2] 0 0
Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis
Timepoint [2] 0 0
Baseline and Month 12
Secondary outcome [3] 0 0
Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
Timepoint [3] 0 0
Baseline and Month 12

Eligibility
Key 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
Minimum age
55 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/01/2015
Sample size
Target
Accrual to date
Final
643
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Research Site - Maroubra
Recruitment hospital [2] 0 0
Research Site - Penrith
Recruitment hospital [3] 0 0
Research Site - St Leonards
Recruitment hospital [4] 0 0
Research Site - Box Hill
Recruitment hospital [5] 0 0
Research Site - Geelong
Recruitment hospital [6] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2035 - Maroubra
Recruitment postcode(s) [2] 0 0
2750 - Penrith
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3220 - Geelong
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Belgium
State/province [8] 0 0
Brussels
Country [9] 0 0
Belgium
State/province [9] 0 0
Brussel
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles
Country [11] 0 0
Belgium
State/province [11] 0 0
Genk
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Belgium
State/province [13] 0 0
Liège
Country [14] 0 0
Belgium
State/province [14] 0 0
Merksem
Country [15] 0 0
Belgium
State/province [15] 0 0
Tessenderlo
Country [16] 0 0
Belgium
State/province [16] 0 0
Wilrijk
Country [17] 0 0
Belgium
State/province [17] 0 0
Yvoir
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Nova Scotia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Denmark
State/province [23] 0 0
Aalborg
Country [24] 0 0
Denmark
State/province [24] 0 0
Ballerup
Country [25] 0 0
Denmark
State/province [25] 0 0
Vejle
Country [26] 0 0
Poland
State/province [26] 0 0
Bialystok
Country [27] 0 0
Poland
State/province [27] 0 0
Kraków
Country [28] 0 0
Poland
State/province [28] 0 0
Torun
Country [29] 0 0
Poland
State/province [29] 0 0
Warszawa
Country [30] 0 0
Spain
State/province [30] 0 0
Andalucía
Country [31] 0 0
Spain
State/province [31] 0 0
Cataluña
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT01732770
Trial related presentations / 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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries