Osteoporosis
Conditions
Keywords
Menopausal Osteoporosis
Brief summary
A randomized, open label study to assess the safety and effectiveness of Denosumab, administered every 6 months and Actonel ® (Risedronate), administered monthly in post menopausal women transitioned from weekly or daily Alendronate therapy.
Interventions
DRUGActonel®
Oral Actonel® (Risedronate) in total a 150mg per month (one 75mg tablet to be taken on each of 2 consecutive days per month).
DRUGDenosumab
Denosumab 60 mg, once every 6 months, Subcutaneous
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, post menopausal women aged 55 years or older at screening. Have received their first prescription of daily or weekly alendronate therapy, for the treatment for post menopausal osteoporosis at least 1 month prior to screening. Use of raloxifene, calcitonin or hormone replacement therapy (HRT) prior to alendronate treatment will be allowed. Prior and/or current use of vitamin D and calcium will be allowed. * Has stopped oral alendronate therapy (is denoted as non-persistent) before the screening visit or, is still taking oral alendronate therapy but does not take on a regular basis (this will be assessed by the completion of a compliance questionnaire at screening). * Provide signed informed consent before any study-specific procedures are conducted.
Exclusion criteria
* Any prior or current use of medications prescribed for osteoporosis treatment other than oral daily alendronate, calcium and vitamin D. Prior use of raloxifen, calcitonin or HRT before alendronate therapy was started will be allowed. * Hypersensitivity to Actonel® or any ingredient of Actonel® tablets. * Contraindicated or poorly tolerant of alendronate therapy. * Active gastric or duodenal ulcer. * Known sensitivity to mammalian cell derived products. * Known intolerance to calcium supplements. * Malignancy within the last 5 years (except for cervical or basal cell carcinoma). * Vitamin D deficiency (serum 25-OH vitamin D less than 20ng/mL (equivalent to 49.9 nanomoles per Liter) at screening. * Current hypo- or hypercalcemia based on the central laboratory reference ranges. * Uncontrolled hyper- or hypothyroidism (stable on antithyroid therapy or post-ablation is allowed, if the laboratory results from screening show that thyroid stimulating hormone (TSH) is within the normal range). * Any metabolic bone disease, e.g., osteomalacia or osteogenesis imperfecta, Paget's disease of bone that may interfere with the interpretation of the findings. * Height, weight or girth which may preclude accurate dual x-ray absorptiometry (DXA measurements). * Fewer than 2 lumbar vertebrae (L1-L4) able to be evaluated by DXA. * Known to have tested positive for human immunodeficiency virus. * Previous participation in clinical trials with denosumab within the last 12 months (regardless of treatment). * Any laboratory abnormality, physical or psychiatric disorder (including substance abuse in last 12 months) which, in the opinion of the investigator, will prevent the subject from giving written informed consent or completing the study or interfere with the interpretation of the study results. * Currently enrolled in or within 30 days of ending another investigational device or drug trial(s).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Hip BMD Percent Change From Baseline at Month 12 | Baseline to month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum CTX Percent Change From Baseline at Month 1 | Baseline to month 1 | Serum Type-1 Collagen C-Telopeptide Percent Change From Baseline at Month 1 |
| Femoral Neck BMD Percent Change From Baseline at Month 12 | Baseline to month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry |
| Lumbar Spine BMD Percent Change From Baseline at Month 12 | Baseline to month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry |
Participant flow
Recruitment details
Participants were enrolled from 19 October 2009 through 4 January 2011
Participants by arm
| Arm | Count |
|---|---|
| Risedronate 150 mg QM Risedronate 150 mg oral once monthly | 435 |
| Denosumab 60 mg Q6M Denosumab 60 mg subcutaneous once every 6 months | 435 |
| Total | 870 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Decision | 0 | 1 |
| Overall Study | Adverse Event | 13 | 3 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Noncompliance | 1 | 0 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Withdrawal by Subject | 15 | 7 |
Baseline characteristics
| Characteristic | Denosumab 60 mg Q6M | Total | Risedronate 150 mg QM |
|---|---|---|---|
| Age, Continuous | 67.8 Years STANDARD_DEVIATION 7 | 67.7 Years STANDARD_DEVIATION 6.9 | 67.7 Years STANDARD_DEVIATION 6.8 |
| Race/Ethnicity, Customized Asian | 3 Participants | 7 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 Participants | 13 Participants | 6 Participants |
| Race/Ethnicity, Customized Japanese | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White or Caucasian | 424 Participants | 849 Participants | 425 Participants |
| Sex: Female, Male Female | 435 Participants | 870 Participants | 435 Participants |
| Sex: Female, Male 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 | 0 / 429 | 0 / 429 |
| serious Total, serious adverse events | 35 / 429 | 33 / 429 |
Outcome results
Primary
Total Hip BMD Percent Change From Baseline at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry
Time frame: Baseline to month 12
Population: All randomized subjects excluding those with missing post baseline data and missing covariate for regression imputation
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Risedronate 150 mg QM | Total Hip BMD Percent Change From Baseline at Month 12 | 0.5 Percent Change From Baseline |
| Denosumab 60 mg Q6M | Total Hip BMD Percent Change From Baseline at Month 12 | 2.0 Percent Change From Baseline |
p-value: <0.000195% CI: [1.2, 2]ANCOVA
Secondary
Femoral Neck BMD Percent Change From Baseline at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry
Time frame: Baseline to month 12
Population: All randomized subjects excluding those with missing post baseline data and missing covariate for regression imputation
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Risedronate 150 mg QM | Femoral Neck BMD Percent Change From Baseline at Month 12 | 0.0 Percent Change From Baseline |
| Denosumab 60 mg Q6M | Femoral Neck BMD Percent Change From Baseline at Month 12 | 1.4 Percent Change From Baseline |
p-value: <0.000195% CI: [0.9, 1.8]ANCOVA
Secondary
Lumbar Spine BMD Percent Change From Baseline at Month 12
Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry
Time frame: Baseline to month 12
Population: All randomized subjects excluding those with missing post baseline data and missing covariate for regression imputation
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Risedronate 150 mg QM | Lumbar Spine BMD Percent Change From Baseline at Month 12 | 1.1 Percent Change From Baseline |
| Denosumab 60 mg Q6M | Lumbar Spine BMD Percent Change From Baseline at Month 12 | 3.4 Percent Change From Baseline |
p-value: <0.000195% CI: [1.8, 2.8]ANCOVA
Secondary
Serum CTX Percent Change From Baseline at Month 1
Serum Type-1 Collagen C-Telopeptide Percent Change From Baseline at Month 1
Time frame: Baseline to month 1
Population: All randomized subjects who enrolled in the bone marker substudy with observed data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Risedronate 150 mg QM | Serum CTX Percent Change From Baseline at Month 1 | -17.0 Percent Change From Baseline |
| Denosumab 60 mg Q6M | Serum CTX Percent Change From Baseline at Month 1 | -77.7 Percent Change From Baseline |
p-value: <0.0001Wilcoxon (Mann-Whitney)