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

Study Overview
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Brief Summary
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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.

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

Conditions
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Postmenopausal Osteoporosis

Intervention / Treatment
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* Drug: Ibandronate
* Drug: Denosumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ibandronate<br>Ibandronate 150mg PO QM (tablet) | Drug: Ibandronate<br>* Ibandronate 150mg PO QM (tablet)<br>|
| Experimental: Denosumab<br>denosumab 60mg Subcutaneous Q6M (pre-filled syringe) | Drug: Denosumab<br>* denosumab 60mg SC Q6M (pre-filled syringe)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 |  | Baseline to month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Type-1 C-Telopeptide Percent Change From Baseline at Month 1 |  | Baseline to month 1 | 
| Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12 |  | Baseline to Month 12 | 
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 |  | Baseline to month 12 |