Overview

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