Osteoporosis
Conditions
Brief summary
Evaluate the efficacy and safety of denosumab in the treatment of involutional (postmenopausal and senile) osteoporotic subjects with prevalent fragility vertebral fracture(s)
Interventions
DRUGDenosumab
Subcutaneous injection every 6 months for 24 months, followed by a 12-month period of denosumab (subcutaneously - every six months).
DRUGPlacebo
Subcutaneous injection every 6 months for 24 months, followed by a 12-month period of denosumab (subcutaneously - every six months).
DRUGAlendronate sodium hydrate
Oral tablet once a week for 24 months
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Involutional (postmenopausal and senile) osteoporosis with prevalent fragility vertebral fractures
Exclusion criteria
* Any underlying condition,(other than BMD) that might have resulted in abnormal bone metabolism
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo | Baseline to 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Non-vertebral Fractures | Baseline to 24 Months | The results are expressed as percentage by Kaplan-Meier estimate the percentage of participants with non-vertebral fractures |
| Percentage of Participants With Hip Fractures in Osteoporotic Participants Treated With Denosumab Compared to Treatment With Placebo. | Baseline to 24 Months | The results are expressed as a percentage by Kaplan-Meier estimate. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Denosumab Denosumab (subcutaneously - every 6 months) + daily calcium and vitamin D supplements for 24 months, followed by a 12-month period of denosumab (subcutaneously - every 6 months). | 472 |
| Placebo Placebo (subcutaneously every 6 months) + daily calcium and vitamin D supplements for 24 months, followed by a 12-month period of denosumab (subcutaneously - every 6 months). | 480 |
| Alendronate Alendronate sodium hydrate oral tablets weekly + daily calcium and vitamin D supplements for 24 months (open label reference arm). | 242 |
| Total | 1,194 |
Baseline characteristics
| Characteristic | Total | Denosumab | Alendronate | Placebo |
|---|---|---|---|---|
| Age, Continuous | 69.6 years STANDARD_DEVIATION 7.49 | 69.9 years STANDARD_DEVIATION 7.36 | 70.2 years STANDARD_DEVIATION 7.31 | 69.0 years STANDARD_DEVIATION 7.67 |
| Region of Enrollment Japan | 1194 participants | 472 participants | 242 participants | 480 participants |
| Sex: Female, Male Female | 1135 Participants | 449 Participants | 230 Participants | 456 Participants |
| Sex: Female, Male Male | 59 Participants | 23 Participants | 12 Participants | 24 Participants |
| the number of participants with vertebral fractures | 1174 Participants | 466 Participants | 237 Participants | 471 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 475 / 475 | 481 / 481 | 242 / 242 |
| serious Total, serious adverse events | 65 / 475 | 68 / 481 | 30 / 242 |
Outcome results
Primary
Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo
Time frame: Baseline to 24 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Denosumab | Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo | 3.6 Vertebral fractures |
| Placebo | Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo | 10.3 Vertebral fractures |
| Alendronate | Incidence of New or Worsening Vertebral Fractures in Osteoporotic Subjects Treated With Denosumab Compared to Placebo | 7.2 Vertebral fractures |
p-value: 0.000195% CI: [0.194, 0.606]Log Rank
Secondary
Percentage of Participants With Hip Fractures in Osteoporotic Participants Treated With Denosumab Compared to Treatment With Placebo.
The results are expressed as a percentage by Kaplan-Meier estimate.
Time frame: Baseline to 24 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab | Percentage of Participants With Hip Fractures in Osteoporotic Participants Treated With Denosumab Compared to Treatment With Placebo. | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Hip Fractures in Osteoporotic Participants Treated With Denosumab Compared to Treatment With Placebo. | 0.5 percentage of participants |
| Alendronate | Percentage of Participants With Hip Fractures in Osteoporotic Participants Treated With Denosumab Compared to Treatment With Placebo. | 0.0 percentage of participants |
p-value: 0.1568Log Rank
Secondary
The Percentage of Non-vertebral Fractures
The results are expressed as percentage by Kaplan-Meier estimate the percentage of participants with non-vertebral fractures
Time frame: Baseline to 24 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab | The Percentage of Non-vertebral Fractures | 4.1 percentage of participants |
| Placebo | The Percentage of Non-vertebral Fractures | 4.1 percentage of participants |
| Alendronate | The Percentage of Non-vertebral Fractures | 2.7 percentage of participants |
p-value: 0.9951Log Rank