Post Menospausal Osteoporosis MedDRA version: 17.0 Level: PT Classification code 10031282 Term: Osteoporosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Prolia
Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: 615258-40-7
CAS Number: 615258-40-7
Oth
Sponsors
Amgen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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 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 (5 mg IV once yearly), on the following: • BMD by DXA of total hip at 12 months (non - inferiority) • BMD by DXA of lumbar spine at 12 months (superiority) • BMD by DXA of total hip at 12 months (superiority);Primary end point(s): Primary Endpoint: • percent change from baseline in lumbar spine BMD at month 12 (non-inferiority);Timepoint(s) of evaluation of this end point: Month 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: • percent change from baseline in total hip BMD at month 12 (non-inferiority) • percent change from baseline in lumbar spine BMD at month 12 (superiority) • percent change from baseline in total hip BMD at month 12 (superiority);Timepoint(s) of evaluation of this end point: Month 12 | — |
Countries
Australia, Belgium, Canada, Denmark, Germany, Poland, Spain, United States
Contacts
Public ContactIHQ Medical Info – Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed