Prostate Cancer
Conditions
Keywords
Prostate Cancer, Bone Loss with Prostate Cancer, Treatment of bone loss in patients undergoing androgen deprivation therapy (ADT) for non-metastatic prostate cancer (PC).
Brief summary
This study will evaluate AMG 162 in the treatment of bone loss in subjects undergoing Androgen-Deprivation Therapy for Non-metastatic Prostate Cancer.
Interventions
DRUGAMG 162
60 mg (1.0mL) administered subcutaneously at Day 1, Months 6, 12, 18, 24, 30
DRUGPlacebo
60 mg (1.0mL) administered subcutaneously at Day 1, Months 6, 12, 18, 24, 30
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Other criteria also apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24 | 24 months | Lumbar Spine Bone Mineral Density Percent Chnage From Baseline at Month 24 Assessed by Dual Energy X-Ray Absorptiometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 24 | 24 months | Total Hip Bone Mineral Density Percent Change From Baseline at Month 24 Assessed by Dual Energy X-Ray Absorptiometry. |
| Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36 | 36 months | Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36 Assessed by Dual Energy X-Ray Absorptiometry. |
| Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 36 | 36 months | Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 36 Assessed by Dual Energy X-Ray Absorptiometry. |
| Total Hip Bone Mineral Density Percent Change From Baseline at Month 36 | 36 months | Total Hip Bone Mineral Density Percent Change From Baseline at Month 36 Assessed by Dual Energy X-Ray Absorptiometry. |
| Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 24 | 24 months | Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 24 Assessed by Dual Energy X-Ray Absorptiometry. |
| Number of Participants With a New Vertebral Fracture Through Month 36 | 36 months | New Vertebral Fracture Assessed by Lateral Spine X-ray using Genant Semiquantitative Scoring Method excluding any symptomatic new vertebral fracture associated with high trauma severity or a pathologic fracture. |
| Time to First Clinical Fracture Through Month 36 | 36 months | A clinical fracture was defined as any nonvertebral fracture or clinically evident fracture at the cervical vertebrae, thoracic vertebrae, and lumbar vertebrae that was associated with signs and/or symptoms indicative of a fracture. Fractures associated with high trauma severity and pathologic (ie, metastatic) fractures were excluded. Since the median time was not reached, time to first clinical fracture is represented by the Kaplan-Meier estimate of the percentage of participants with a clinical fracture. |
| Number of Participants With Any Fracture Through Month 24 | 24 months | Any fracture includes osteroporotic fractures at any site excluding skull, facial, mandible, metacarpals, finger phalanges, and toe phalanges. |
| Number of Participants With Any Fracture Through Month 36 | 36 months | Any fracture includes osteroporotic fractures at any site excluding skull, facial, mandible, metacarpals, finger phalanges, and toe phalanges. |
Participant flow
Recruitment details
First Subject Enrolled: 15-Apr-2004 Last Subject Enrolled: 29-Apr-2005
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered subcutaneous every 6 months for 3 years | 734 |
| Denosumab 60 mg Q6M Denosumab 60 mg administered subcutaneous (SC) every 6 months for 3 years | 734 |
| Total | 1,468 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 23 | 29 |
| Overall Study | Death | 43 | 43 |
| Overall Study | Disease progression | 21 | 23 |
| Overall Study | Ineligibility determined | 8 | 10 |
| Overall Study | Lost to Follow-up | 21 | 17 |
| Overall Study | Noncompliance | 7 | 3 |
| Overall Study | Other | 5 | 9 |
| Overall Study | Physician Decision | 4 | 2 |
| Overall Study | Requirement for alternative therapy | 14 | 4 |
| Overall Study | Withdrawal by Subject | 143 | 127 |
Baseline characteristics
| Characteristic | Placebo | Denosumab 60 mg Q6M | Total |
|---|---|---|---|
| Age, Continuous | 75.5 Years STANDARD_DEVIATION 7.1 | 75.3 Years STANDARD_DEVIATION 7 | 75.4 Years STANDARD_DEVIATION 7.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 5 Participants | 8 Participants |
| Race/Ethnicity, Customized Black or African American | 32 Participants | 36 Participants | 68 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 81 Participants | 77 Participants | 158 Participants |
| Race/Ethnicity, Customized Japanese | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White or Caucasian | 609 Participants | 615 Participants | 1224 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 734 Participants | 734 Participants | 1468 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 364 / 725 | 390 / 731 |
| serious Total, serious adverse events | 222 / 725 | 253 / 731 |
Outcome results
Primary
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24
Lumbar Spine Bone Mineral Density Percent Chnage From Baseline at Month 24 Assessed by Dual Energy X-Ray Absorptiometry.
Time frame: 24 months
Population: Randomized subjects who had a nonmissing baseline and \>= 1 nonmissing postbaseline data before or at month 24. LOCF used as imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24 | -1 Percent Change from Baseline |
| Denosumab 60 mg Q6M | Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24 | 5.6 Percent Change from Baseline |
p-value: <0.000195% CI: [6.2, 7.1]ANCOVA
Secondary
Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 24
Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 24 Assessed by Dual Energy X-Ray Absorptiometry.
Time frame: 24 months
Population: Randomized subjects who had a nonmissing baseline and \>= 1 nonmissing postbaseline data before or at month 24. LOCF used as imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 24 | -1.5 Percent Change from Baseline |
| Denosumab 60 mg Q6M | Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 24 | 2.4 Percent Change from Baseline |
p-value: <0.000195% CI: [3.5, 4.4]ANCOVA
Secondary
Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 36
Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 36 Assessed by Dual Energy X-Ray Absorptiometry.
Time frame: 36 months
Population: Randomized subjects who had a nonmissing baseline and \>= 1 nonmissing postbaseline data before or at month 36. LOCF used as imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 36 | -1.8 Percent Change from Baseline |
| Denosumab 60 mg Q6M | Femoral Neck Bone Mineral Density Percent Change From Baseline at Month 36 | 3 Percent Change from Baseline |
p-value: <0.000195% CI: [4.4, 5.4]ANCOVA
Secondary
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36 Assessed by Dual Energy X-Ray Absorptiometry.
Time frame: 36 months
Population: Randomized subjects who had a nonmissing baseline and \>= 1 nonmissing postbaseline data before or at month 36. LOCF used as imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36 | -1.2 Percent Change from Baseline |
| Denosumab 60 mg Q6M | Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36 | 6.8 Percent Change from Baseline |
p-value: <0.000195% CI: [7.4, 8.4]ANCOVA
Secondary
Number of Participants With a New Vertebral Fracture Through Month 36
New Vertebral Fracture Assessed by Lateral Spine X-ray using Genant Semiquantitative Scoring Method excluding any symptomatic new vertebral fracture associated with high trauma severity or a pathologic fracture.
Time frame: 36 months
Population: All randomized subjects who have a baseline and \>= 1 postbaseline evaluation of vertebral fracture at or before 3 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With a New Vertebral Fracture Through Month 36 | 26 Participants |
| Denosumab 60 mg Q6M | Number of Participants With a New Vertebral Fracture Through Month 36 | 10 Participants |
p-value: 0.012595% CI: [0.18, 0.78]Regression, Logistic
Secondary
Number of Participants With Any Fracture Through Month 24
Any fracture includes osteroporotic fractures at any site excluding skull, facial, mandible, metacarpals, finger phalanges, and toe phalanges.
Time frame: 24 months
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Any Fracture Through Month 24 | 45 Participants |
| Denosumab 60 mg Q6M | Number of Participants With Any Fracture Through Month 24 | 32 Participants |
p-value: 0.796195% CI: [0.44, 1.11]Regression, Logistic
Secondary
Number of Participants With Any Fracture Through Month 36
Any fracture includes osteroporotic fractures at any site excluding skull, facial, mandible, metacarpals, finger phalanges, and toe phalanges.
Time frame: 36 months
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Any Fracture Through Month 36 | 53 Participants |
| Denosumab 60 mg Q6M | Number of Participants With Any Fracture Through Month 36 | 38 Participants |
p-value: 0.104895% CI: [0.46, 1.08]Regression, Logistic
Secondary
Time to First Clinical Fracture Through Month 36
A clinical fracture was defined as any nonvertebral fracture or clinically evident fracture at the cervical vertebrae, thoracic vertebrae, and lumbar vertebrae that was associated with signs and/or symptoms indicative of a fracture. Fractures associated with high trauma severity and pathologic (ie, metastatic) fractures were excluded. Since the median time was not reached, time to first clinical fracture is represented by the Kaplan-Meier estimate of the percentage of participants with a clinical fracture.
Time frame: 36 months
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to First Clinical Fracture Through Month 36 | 5.2 Percentage of participants |
| Denosumab 60 mg Q6M | Time to First Clinical Fracture Through Month 36 | 4.7 Percentage of participants |
p-value: 0.796195% CI: [0.57, 1.55]Regression, Cox
Secondary
Total Hip Bone Mineral Density Percent Change From Baseline at Month 24
Total Hip Bone Mineral Density Percent Change From Baseline at Month 24 Assessed by Dual Energy X-Ray Absorptiometry.
Time frame: 24 months
Population: Randomized subjects who had a nonmissing baseline and \>= 1 nonmissing postbaseline data before or at month 24. LOCF used as imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Total Hip Bone Mineral Density Percent Change From Baseline at Month 24 | -2 Percent Change from Baseline |
| Denosumab 60 mg Q6M | Total Hip Bone Mineral Density Percent Change From Baseline at Month 24 | 2.7 Percent Change from Baseline |
p-value: <0.000195% CI: [4.4, 5.1]ANCOVA
Secondary
Total Hip Bone Mineral Density Percent Change From Baseline at Month 36
Total Hip Bone Mineral Density Percent Change From Baseline at Month 36 Assessed by Dual Energy X-Ray Absorptiometry.
Time frame: 36 months
Population: Randomized subjects who had a nonmissing baseline and \>= 1 nonmissing postbaseline data before or at month 36. LOCF used as imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Total Hip Bone Mineral Density Percent Change From Baseline at Month 36 | -2.6 Percent Change from Baseline |
| Denosumab 60 mg Q6M | Total Hip Bone Mineral Density Percent Change From Baseline at Month 36 | 3.2 Percent Change from Baseline |
p-value: <0.000195% CI: [5.4, 6.1]ANCOVA