Clinical trial NCT01732770: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Post Menopausal Osteoporosis
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2012-11-26
Enrollment: 643
Sex: FEMALE
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis
timeFrame: Baseline and Month 12
Secondary outcomes:
measure: Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis
timeFrame: Baseline and Month 12
measure: Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis
timeFrame: Baseline and Month 12
measure: Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
timeFrame: Baseline and Month 12
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Lakewood
country: United States
facility: Research Site
state: Colorado
city: Longmont
country: United States
facility: Research Site
state: Colorado
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Hagerstown
country: United States
facility: Research Site
state: Maryland
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: West Haverstraw
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: Maroubra
country: Australia
facility: Research Site
state: New South Wales
city: Penrith
country: Australia
facility: Research Site
state: New South Wales
city: St Leonards
country: Australia
facility: Research Site
state: New South Wales
city: Box Hill
country: Australia
facility: Research Site
state: Victoria
city: Geelong
country: Australia
facility: Research Site
state: Victoria
city: Parkville
country: Australia
facility: Research Site
state: Victoria
city: Brussels
country: Belgium
facility: Research Site
city: Brussel
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Genk
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liège
country: Belgium
facility: Research Site
city: Merksem
country: Belgium
facility: Research Site
city: Tessenderlo
country: Belgium
facility: Research Site
city: Wilrijk
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Quebec
country: Canada
facility: Research Site
city: Aalborg
country: Denmark
facility: Research Site
city: Ballerup
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Torun
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Granada
country: Spain
facility: Research Site
state: Andalucía
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
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.
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.
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.