A Study to Evaluate the Safety and Efficacy of Denosumab and Ibandronate in Postmenopausal Women Sub-Optimally Treated With Daily or Weekly Bisphosphonates
Condition: Postmenopausal Osteoporosis
MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal
Intervention: Ibandronate; Denosumab
Intervention description: Ibandronate 150mg PO QM (tablet); denosumab 60mg SC Q6M (pre-filled syringe)
Intervention MeSH terms: Denosumab; Ibandronic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 833.0
Sex: Female
Minimum age: 55 Years
Healthy volunteers: No

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