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

Phase 3

Completed

Conditions: Postmenopausal Osteoporosis

Interventions: Drug: Denosumab
Drug: Ibandronate

Registration Number: NCT00936897

Lead Sponsor: Amgen

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 833

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Denosumab	Denosumab	denosumab 60mg Subcutaneous Q6M (pre-filled syringe)
Ibandronate	Ibandronate	Ibandronate 150mg PO QM (tablet)

Primary Outcome Measures

Name	Time	Method
Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	Baseline to month 12

Secondary Outcome Measures

Name	Time	Method
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