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

Conditions: Post Menospausal Osteoporosis
MedDRA version: 15.0Level: PTClassification code 10031282Term: OsteoporosisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

Registration Number: EUCTR2012-001821-28-ES

Lead Sponsor: Amgen, Inc.

Brief Summary: Not available

Detailed Description: Not available

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
..IV bisphosphonate other than zoledronic acid
..fluoride or strontium at doses approved for OP
..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 investigational device or drug study(s)
- Other investigational procedures while pa

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate if the effect of administering denosumab (60 mg subcutaneously [SC] every 6 months [Q6M]) is not inferior to that of zoledronic acid (5 mg<br>intravenously [IV] once yearly) in postmenopausal women with osteoporosis previously treated with oral bisphosphonates with respect to change in bone mineral density (BMD) by dual energy<br>x-ray absorptiometry (DXA) of lumbar spine at 12 months.;Secondary Objective: Compare the efficacy of administering denosumab (60 mg SC Q6M), with that of zoledronic acid<br>(5 mg IV once yearly), on the following:<br>- BMD by DXA of total hip at 12 months (non - inferiority)<br>- BMD by DXA of lumbar spine at 12 months (superiority)<br>- BMD by DXA of total hip at 12 months (superiority);Primary end point(s): Primary Endpoint:<br>- percent change from baseline in lumbar spine BMD at month 12 (non-inferiority);Timepoint(s) of evaluation of this end point: Month 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary Endpoints:<br>- percent change from baseline in total hip BMD at month 12 (non-inferiority)<br>- percent change from baseline in lumbar spine BMD at month 12 (superiority)<br>- percent change from baseline in total hip BMD at month 12 (superiority);Timepoint(s) of evaluation of this end point: Month 12

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