a study to evaluate the safety and efficacy of denosumab and ibandronate in postmenopausal women sub-optimally treated with daily or weekly bisphosphonates

Conditions: Postmenopausal Osteoporosis

Summary: this is a multi-center, randomized, open-label, parallel group, study being conducted in the united states and in europe in postmenopausal women. approximately 800 subjects will be randomized across about 65 sites in a 1:1 ratio to either denosumab 60mg sc q6m, or ibandronate 150mg po qm.


Eligibility criteria:
inclusion criteria: * ambulatory, postmenopausal women (based on medical history) 55 years or older at screening * postmenopause will be defined as no vaginal bleeding or spotting for at least 12 months * if the subject is 55 - 59 years old and there is uncertainty regarding menopausal status, confirmation of serum fsh (\>= 50 miu/ml) and serum estradiol (\<= 20 pg/ml) must be obtained * if the subject is 60 years or older, evaluation of fsh and estradiol levels is not needed to confirm menopausal status * have received their first prescription of daily or weekly bisphosphonate therapy at least 1 month prior to screening * may have received * raloxifene, calcitonin, prior to initiation of daily orweekly bisphosphonate therapy. * up to 3 doses of monthly bisphosphonate prior to initiation of daily or weekly bisphosphonate therapy * calcium, and vitamin d * hormone replacement therapy (e.g. estrogen use for mitigation of menopausal symptoms) * subject has: * stopped daily or weekly bisphosphonate therapy (is denoted as non-persistent) at least one month before the screening visit, or * demonstrated low adherence to therapy assessed by a score of less than 6 on the os-mmas * screening bmd (g/cm2) values, at the lumbar spine or total hip, that occur within the following ranges, based on the particular scanner that is used: ge lunar lumbar spine 0.700 \< or = bmd \< and = 0.940 total hip 0.504 \< or = bmd \< or = 0.756 hologic lumbar spine 0.607 \< or = bmd \< or = 0.827 total hip 0.454 \< or = bmd \< or = 0.698 both the initial and the repeat dxa scan of the lumbar spine or the total hip must meet the above eligibility criteria. * at least 2 lumbar vertebrae must be evaluable by dxa. * at least one hip must be evaluable by dxa (eg, no history of either bilateral hip replacement or pins in both hips) * provide signed informed consent before any study-specific procedures are conducted exclusion criteria: * any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures * current or prior use of medications prescribed for osteoporosis treatment other than oral daily or weekly bisphosphonate * contraindicated to receive oral ibandronate 150mg po qm, including * hypersensitivity to ibandronate 150mg po qm or other constituents of ibandronate 150mg po qm tablets * abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia * inability to stand or sit upright for at least 60 minutes * administration of any of the following treatments within 3 months of screening * 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) * vitamin d deficiency \[25(oh) vitamin d level \< 20 ng/ml (\<49.9 nmol/l)\] - repletion will be allowed and subjects may be re-screened * evidence of any of the following per subject report, chart review or central laboratory result: * significantly impaired renal function as determined by estimated glomerular filtration rate less that 30ml/min/1.73 m2 determined by the central laboratory * current hypo- or hypercalcemia based on the central laboratory reference ranges * active gastric or duodenal ulcer; or any history of significant gastrointestinal bleed requiring hospitalization or transfusion * known to have tested positive for human immunodeficiency virus, hepatitis c virus, or hepatitis b surface antigen * malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years * any metabolic bone disease or secondary cause of bone loss that is not controlled and may interfere with the interpretation of the findings * previous participation in clinical trials with denosumab 60mg sc q6m (regardless of treatment) * received any solid organ or bone marrow transplant * any laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results * known sensitivity to mammalian cell derived drug products * known intolerance to calcium supplements * currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s) * any physical or psychiatric disorder which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results * evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study