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

Condition(s) targeted: Postmenopausal Osteoporosis

Intervention: Ibandronate (Drug); Denosumab (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Amgen

Official(s) and/or principal investigator(s):
MD, Study Director, Affiliation: Amgen

Overall contact:
Amgen Call Center, Phone: 866-572-6436

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: 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

Study design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

The primary endpoint is percent change from baseline in BMD at the total hip at 12 months

To evaluate safety and tolerability measured by evaluating adverse events, antidenosumab antibodies and laboratory analytes over 12 months

Secondary outcome:

To evaluate the effects of transitioning to denosumab 60mg SC Q6M in comparison to transitioning to ibandronate 150mg PO QM on sCTX-1 levels at 1 month (in a subset of subjects).

To evaluate the effects of transitioning to denosumab 60mg SC Q6M in comparison to transitioning to ibandronate 150mg PO QM on BMD at the femoral neck at 12 months.

To evaluate the effects of transitioning to denosumab 60mg SC Q6M in comparison to transitioning to ibandronate 150mg PO QM on BMD at the lumbar spine at 12 months.

Minimum age: 55 Years. Maximum age: N/A. Gender(s): Female.

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 - 60 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 greater than 60 years old, 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 6 months but no more than 18 months prior to screening

- May have received

- raloxifene, calcitonin, prior to initiation of bisphosphonate therapy.

- calcium, and vitamin D

- Hormone replacement therapy (e. g. estrogen use for mitigation of menopausal

symptoms)

- Subject has:

- Stopped 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 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

- 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

Amgen Call Center, Phone: 866-572-6436

Research Site, Montpellier, France

Research Site, Huntsville, Alabama, United States

Research Site, Tucson, Arizona, United States

Research Site, Peoria, Arizona, United States

Research Site, Litchfield Park, Arizona, United States

Research Site, Mesa, Arizona, United States

Research Site, Phoenix, Arizona, United States

Research Site, Walnut Creek, California, United States

Research Site, Sacramento, California, United States

Research Site, Laguna Hills, California, United States

Research Site, San Diego, California, United States

Research Site, Upland, California, United States

Research Site, Leesburg, Florida, United States

Research Site, Gainesville, Georgia, United States

Research Site, Sandy Springs, Georgia, United States

Research Site, Boise, Idaho, United States

Research Site, Shreveport, Louisiana, United States

Research Site, Bethesda, Maryland, United States

Research Site, Brockton, Massachusetts, United States

Research Site, Paw Paw, Michigan, United States

Research Site, Detroit, Michigan, United States

Research Site, Billings, Montana, United States

Research Site, Edison, New Jersey, United States

Research Site, Freehold, New Jersey, United States

Research Site, Endwell, New York, United States

Research Site, Asheville, North Carolina, United States

Research Site, Hickory, North Carolina, United States

Research Site, Fargo, North Dakota, United States

Research Site, Duncansville, Pennsylvania, United States

Research Site, Kingsport, Tennessee, United States

Research Site, Houston, Texas, United States

Research Site, Denton, Texas, United States

Research Site, San Antonio, Texas, United States

Research Site, Lakewood, Washington, United States

Research Site, Charleston, West Virginia, United States

AmgenTrials clinical trials website

Starting date: July 2009
Ending date: September 2011
Last updated: October 15, 2009