Postmenopausal Osteoporosis
Conditions
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.
Interventions
DRUGIbandronate
Ibandronate 150mg PO QM (tablet)
DRUGDenosumab
denosumab 60mg SC Q6M (pre-filled syringe)
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
55 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 | Baseline to month 12 |
Secondary
| Measure | 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 |
Participant flow
Recruitment details
Participants were randomized from 29 July 2009 through 5 November 2010
Participants by arm
| Arm | Count |
|---|---|
| Denosumab 60 mg SC Q6M Denosumab 60 mg subcutaneous once every 6 months | 417 |
| Ibandronate 150 mg PO QM Ibandronate 150 mg oral monthly | 416 |
| Total | 833 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Decision | 1 | 2 |
| Overall Study | Adverse Event | 4 | 13 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Ineligibility Determined | 0 | 3 |
| Overall Study | Lost to Follow-up | 1 | 10 |
| Overall Study | Noncompliance | 0 | 2 |
| Overall Study | Other | 3 | 9 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 19 |
Baseline characteristics
| Characteristic | Denosumab 60 mg SC Q6M | Ibandronate 150 mg PO QM | Total |
|---|---|---|---|
| Age Continuous | 67.2 Years STANDARD_DEVIATION 8.1 | 66.2 Years STANDARD_DEVIATION 7.8 | 66.7 Years STANDARD_DEVIATION 8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 54 Participants | 42 Participants | 96 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 6 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White or Caucasian | 348 Participants | 361 Participants | 709 Participants |
| Sex/Gender, Customized Female | 417 Participants | 416 Participants | 833 Participants |
| Sex/Gender, Customized Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 410 | 42 / 411 |
| serious Total, serious adverse events | 22 / 410 | 39 / 411 |
Outcome results
Primary
Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: Baseline to month 12
Population: All randomized subjects using regression imputation for missing post baseline data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Denosumab 60 mg SC Q6M | Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 | 2.2 Percentage Change From Baseline |
| Ibandronate 150 mg PO QM | Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 | 0.9 Percentage Change From Baseline |
p-value: <0.000195% CI: [1, 1.8]ANCOVA
Secondary
Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: Baseline to Month 12
Population: All randomized subjects using regression imputation for missing post baseline data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Denosumab 60 mg SC Q6M | Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12 | 1.7 Percentage Change From Baseline |
| Ibandronate 150 mg PO QM | Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 12 | 0.5 Percentage Change From Baseline |
p-value: <0.000195% CI: [0.7, 1.7]ANCOVA
Secondary
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12
Time frame: Baseline to month 12
Population: All randomized subjects using regression imputation for missing post baseline data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Denosumab 60 mg SC Q6M | Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 | 4.1 Percentage Change From Baseline |
| Ibandronate 150 mg PO QM | Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 | 2.1 Percentage Change From Baseline |
p-value: <0.000195% CI: [1.5, 2.5]ANCOVA
Secondary
Serum Type-1 C-Telopeptide Percent Change From Baseline at Month 1
Time frame: Baseline to month 1
Population: Randomized subjects who enrolled in the bone marker substudy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denosumab 60 mg SC Q6M | Serum Type-1 C-Telopeptide Percent Change From Baseline at Month 1 | -81.1 Percentage Change From Baseline |
| Ibandronate 150 mg PO QM | Serum Type-1 C-Telopeptide Percent Change From Baseline at Month 1 | -35.0 Percentage Change From Baseline |
p-value: <0.0001Wilcoxon (Mann-Whitney)