A Study to Evaluate the Safety and Efficacy of Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 620

Inclusion Criteria

- Subject or subject’s legally acceptable representative has provided informed consent prior to any study specific procedure(s)
- Ambulatory postmenopausal women. Ambulatory is defined as women who are able to walk, not bedridden; postmenopause is defined as no vaginal bleeding or spotting for at least 12 months prior to screening.
- Age 55 years or older
- Received oral bisphosphonate therapy for OP for at least 2 years immediately 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. Eligibility will be determined by a local reading of the DXAs at the investigator site. At least 2 lumbar vertebrae and one hip must be evaluable by DXA at the screening visit.
- Serum CTX value of = 0.5 ng/mL at the screening visit as determined by central laboratory
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 440

Exclusion Criteria

- Height, weight or girth which may preclude accurate DXA measurements
- Received other OP treatment or bone active treatment with the following guidelines
• administration of denosumab or zoledronic acid at any time
• administration of the following within the last 5 years
o IV bisphosphonate other than zoledronic acid
o fluoride or strontium at doses approved for OP
o PTH or PTH derivatives within the last year
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)
Administration of any of the following treatment within 3 months of screening:
• any selective estrogen receptor modulator (estrogen agonist antagonist)
• tibolone
• anabolic steroids or testosterone
• glucocorticosteroids (= 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of = 50 mg)
• systemic hormone replacement therapy (HRT) (subjects stable on HRT for more than 3 months prior is permitted)
• calcitonin
• other bone active drugs including anti-convulsants (except
benzodiazepines) and heparin
• cathepsin K inhibitor
• anti-sclerostin antibody
• chronic systemic ketoconazole, androgens, adrenocorticotrophic
hormone, cinacalcet, aluminum, lithium, protease inhibitors,
gonadotropin- releasing hormone agonists
- 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
• known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen
• osteomalacia (chart review)
• osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal and/or pre-existing dental disease
• 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)
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
- Contraindicated or poorly tolerant of denosumab therapy; contraindications include
• hypocalcemia
• hypersensitivity to drug or any component of the drug
- Contraindicated or poorly tolerant of zoledronic acid therapy;
contraindications include the following:
• hypocalcemia
• subjects with creatinine clearance of <35 mL/min and in those with evidence of acute renal impairment (calculated using Cockcroft Gault equation)
• hypersensitivity to any component of zoledronic acid solution
- Known intolerance to calcium or vitamin D supplements
- For women of child bearing potential: refusal to use 2 highly effective forms of contraception and to continue this practice for 7 months after last injection of study medication
- 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 investigation

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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