A Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated With Daily or Weekly Bisphosphonates

• Status: Completed
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Amgen
• Treatments: Denosumab; Diphosphonates; Ibandronic Acid

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