Osteoporosis
Conditions
Keywords
Postmenopausal Osteoporosis
Brief summary
This study will evaluate the effectiveness and safety of denosumab in treating women with Postmenopausal Osteoporosis.
Interventions
DRUGplacebo
Placebo administered by subcutaneous injection
DRUGDenosumab
Denosumab 60 mg administered by subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
60 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Women who are 60 to 90 years of age may be eligible to participate * Bone mineral density (BMD) T-Score at hip or spine must be less than -2.5
Exclusion criteria
* BMD T-Score at the hip or the spine of less than -4.0 * Patients with any severe or more than two moderate vertebral fractures on spinal x-ray at entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With New Vertebral Fractures | 36 months | A new vertebral fracture, assessed by lateral spine X-ray using Genant semiquantitative scoring method, was identified as an ≥ 1 grade increase from the Baseline grade of 0 in any vertebra from T4 to L4. New vertebral fractures included morphometric vertebral fractures (assessed at scheduled visits and not associated with signs or symptoms \[or both\] indicative of a fracture) and clinical vertebral fractures (assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms indicative of a fracture, excluding any fracture associated with high trauma severity or a pathologic fracture). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Nonvertebral Fractures | 36 months | Nonvertebral fractures (osteoporotic) were those occurring on study excluding those of the vertebrae (cervical, thoracic, and lumbar), skull, facial, mandible, metacarpus, finger phalanges, and toe phalanges. Fractures associated with high trauma severity (fractures that were the result of a fall from higher than the height of a stool, chair, first rung on a ladder or equivalent (\> 20 inches) or was the result of severe trauma other than a fall) and pathologic fractures were excluded from this category. Nonvertebral fractures were required to be confirmed either by radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging (MRI), or by documentation in a radiology report, surgical report, or discharge summary. |
| Number of Participants With a Hip Fracture | 36 months | Hip fractures are a subset of nonvertebral fractures including femur neck, femur intertrochanter, and femur subtrochanter. |
Participant flow
Recruitment details
First Subject Enrolled: 03-Aug-2004 Last Subject Enrolled: 01-Jun-2005
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered subcutaneously once every 6 months for 3 years. | 3,906 |
| Denosumab 60 mg Q6M Denosumab 60 mg administered subcutaneously once every 6 months (Q6M) for 3 years. | 3,902 |
| Total | 7,808 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 81 | 93 |
| Overall Study | Death | 78 | 62 |
| Overall Study | Disease progression | 7 | 3 |
| Overall Study | Ineligibility determined | 12 | 9 |
| Overall Study | Lost to Follow-up | 57 | 57 |
| Overall Study | Noncompliance | 17 | 13 |
| Overall Study | Other | 20 | 32 |
| Overall Study | Physician Decision | 6 | 3 |
| Overall Study | Protocol deviation | 12 | 10 |
| Overall Study | Requirement for alternative therapy | 7 | 4 |
| Overall Study | Withdrawal by Subject | 403 | 344 |
Baseline characteristics
| Characteristic | Placebo | Denosumab 60 mg Q6M | Total |
|---|---|---|---|
| Age, Continuous | 72.3 Years STANDARD_DEVIATION 5.2 | 72.3 Years STANDARD_DEVIATION 5.2 | 72.3 Years STANDARD_DEVIATION 5.2 |
| Race/Ethnicity, Customized Asian | 8 Participants | 9 Participants | 17 Participants |
| Race/Ethnicity, Customized Black or African American | 27 Participants | 30 Participants | 57 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 232 Participants | 241 Participants | 473 Participants |
| Race/Ethnicity, Customized Japanese | 4 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 6 Participants | 10 Participants |
| Race/Ethnicity, Customized White or Caucasian | 3629 Participants | 3609 Participants | 7238 Participants |
| Sex: Female, Male Female | 3906 Participants | 3902 Participants | 7808 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 | 3,107 / 3,876 | 3,073 / 3,886 |
| serious Total, serious adverse events | 972 / 3,876 | 1,004 / 3,886 |
Outcome results
Primary
Number of Participants With New Vertebral Fractures
A new vertebral fracture, assessed by lateral spine X-ray using Genant semiquantitative scoring method, was identified as an ≥ 1 grade increase from the Baseline grade of 0 in any vertebra from T4 to L4. New vertebral fractures included morphometric vertebral fractures (assessed at scheduled visits and not associated with signs or symptoms \[or both\] indicative of a fracture) and clinical vertebral fractures (assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms indicative of a fracture, excluding any fracture associated with high trauma severity or a pathologic fracture).
Time frame: 36 months
Population: Primary Efficacy Analysis Set, which includes all randomized participants who have a baseline and ≥ 1 postbaseline evaluation of vertebral fracture at or before 3 years. Last Observation Carried Forward was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With New Vertebral Fractures | 264 Participants |
| Denosumab 60 mg Q6M | Number of Participants With New Vertebral Fractures | 86 Participants |
p-value: <0.000195% CI: [0.26, 0.41]Mantel Haenszel
Secondary
Number of Participants With a Hip Fracture
Hip fractures are a subset of nonvertebral fractures including femur neck, femur intertrochanter, and femur subtrochanter.
Time frame: 36 months
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With a Hip Fracture | 43 Participants |
| Denosumab 60 mg Q6M | Number of Participants With a Hip Fracture | 26 Participants |
p-value: 0.036295% CI: [0.37, 0.97]Regression, Cox
Secondary
Number of Participants With Nonvertebral Fractures
Nonvertebral fractures (osteoporotic) were those occurring on study excluding those of the vertebrae (cervical, thoracic, and lumbar), skull, facial, mandible, metacarpus, finger phalanges, and toe phalanges. Fractures associated with high trauma severity (fractures that were the result of a fall from higher than the height of a stool, chair, first rung on a ladder or equivalent (\> 20 inches) or was the result of severe trauma other than a fall) and pathologic fractures were excluded from this category. Nonvertebral fractures were required to be confirmed either by radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging (MRI), or by documentation in a radiology report, surgical report, or discharge summary.
Time frame: 36 months
Population: Full analysis set (all randomized participants)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Nonvertebral Fractures | 293 Participants |
| Denosumab 60 mg Q6M | Number of Participants With Nonvertebral Fractures | 238 Participants |
p-value: 0.010695% CI: [0.67, 0.95]Regression, Cox