Osteoporosis in Men
Conditions
Keywords
Osteoporosis in men
Brief summary
The study is designed to evaluate if treatment with romosozumab once a month for 12 months compared with placebo is effective in increasing bone mineral density (BMD) at the lumbar spine. Additionally, the study will assess the effect of treatment with romosozumab for 12 months compared with placebo on BMD at the femoral neck and total hip.
Interventions
BIOLOGICALRomosozumab
Administered by subcutaneous injection once a month.
DRUGPlacebo
Administered by subcutaneous injection once a month.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
55 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Must be ambulatory male subjects ≥ 55 years to ≤ 90 years of age * Must have a BMD T score ≤ -2.50 at the spine or hip, or BMD T score ≤ -1.50 at the spine or hip and a history of fragility nonvertebral fracture or vertebral fracture.
Exclusion criteria
* A BMD T score ≤ -3.50 at the hip, * History of hip fracture * Severe metabolic bone diseases * Significant laboratory abnormalities * Recent treatment with agents affecting bone metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 12 | Baseline and month 12 | Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in BMD at the Total Hip at Month 12 | Baseline and month 12 | Total hip bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in BMD at the Femoral Neck at Month 12 | Baseline and month 12 | Femoral neck bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in Lumbar Spine BMD at Month 6 | Baseline and month 6 | Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in BMD at the Total Hip at Month 6 | Baseline and month 6 | Bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
| Percent Change From Baseline in BMD at the Femoral Neck at Month 6 | Baseline and month 6 | Bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. |
Countries
Belgium, Colombia, Czechia, Denmark, Japan, Mexico, Poland, Russia, Switzerland, United States
Participant flow
Recruitment details
This study was conducted at 31 centers in Europe, North America, Latin America, and Japan. Participants were enrolled from 16 June 2014 to 27 January 2015.
Pre-assignment details
Participants were randomized in a 2:1 ratio to receive 210 mg romosozumab or matched placebo in a blinded fashion for the duration of the 12-month treatment period. Randomization was stratified by geographic region (Europe, North America, Latin America, and Japan).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo subcutaneous injections once a month (QM) for 12 months. | 82 |
| Romosozumab 210 mg Participants received 210 mg romosozumab administered by subcutaneous injection once a month for 12 months. | 163 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol-specified Criteria | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 9 |
Baseline characteristics
| Characteristic | Placebo | Romosozumab 210 mg | Total |
|---|---|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 6.9 | 72.4 years STANDARD_DEVIATION 7.4 | 72.1 years STANDARD_DEVIATION 7.3 |
| Age, Customized 18 - 64 years | 11 Participants | 31 Participants | 42 Participants |
| Age, Customized 65 - 74 years | 42 Participants | 62 Participants | 104 Participants |
| Age, Customized 75 years and over | 29 Participants | 70 Participants | 99 Participants |
| Femoral Neck BMD T-score | -2.30 T-score STANDARD_DEVIATION 0.52 | -2.34 T-score STANDARD_DEVIATION 0.52 | -2.33 T-score STANDARD_DEVIATION 0.52 |
| Geographic Region Europe | 54 Participants | 108 Participants | 162 Participants |
| Geographic Region Japan | 9 Participants | 18 Participants | 27 Participants |
| Geographic Region Latin America | 12 Participants | 23 Participants | 35 Participants |
| Geographic Region North America | 7 Participants | 14 Participants | 21 Participants |
| Lumbar Spine Bone Mineral Density T-score | -2.33 T-score STANDARD_DEVIATION 1.41 | -2.22 T-score STANDARD_DEVIATION 1.19 | -2.26 T-score STANDARD_DEVIATION 1.27 |
| Race Asian | 9 Participants | 18 Participants | 27 Participants |
| Race Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race Multiple | 0 Participants | 1 Participants | 1 Participants |
| Race Other | 13 Participants | 23 Participants | 36 Participants |
| Race White | 60 Participants | 120 Participants | 180 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 82 Participants | 163 Participants | 245 Participants |
| Total Hip BMD T-score | -1.92 T-score STANDARD_DEVIATION 0.65 | -1.92 T-score STANDARD_DEVIATION 0.59 | -1.92 T-score STANDARD_DEVIATION 0.61 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 81 | 74 / 163 |
| serious Total, serious adverse events | 10 / 81 | 23 / 163 |
Outcome results
Primary
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 12
Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 12
Population: Primary efficacy analysis subset, which includes all randomized participants who had a baseline DXA BMD measurement and at least 1 post-baseline DXA BMD measurement at the lumbar spine; last observation carried forward (LOCF) imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 12 | 1.2 percent change | Standard Error 0.5 |
| Romosozumab 210 mg | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 12 | 12.1 percent change | Standard Error 0.5 |
p-value: <0.000195% CI: [9.6, 12.2]ANCOVA
Secondary
Percent Change From Baseline in BMD at the Femoral Neck at Month 12
Femoral neck bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 12
Population: Primary efficacy analysis subset, which includes all randomized participants who had a baseline DXA BMD measurement and at least 1 post-baseline DXA BMD measurement at the femoral neck; LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in BMD at the Femoral Neck at Month 12 | -0.2 percent change | Standard Error 0.4 |
| Romosozumab 210 mg | Percent Change From Baseline in BMD at the Femoral Neck at Month 12 | 2.2 percent change | Standard Error 0.4 |
p-value: <0.000195% CI: [1.5, 3.3]ANCOVA
Secondary
Percent Change From Baseline in BMD at the Femoral Neck at Month 6
Bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 6
Population: Primary efficacy analysis subset with available data at baseline and month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in BMD at the Femoral Neck at Month 6 | 0.0 percent change | Standard Error 0.4 |
| Romosozumab 210 mg | Percent Change From Baseline in BMD at the Femoral Neck at Month 6 | 1.2 percent change | Standard Error 0.3 |
p-value: =0.003395% CI: [0.4, 2.1]ANCOVA
Secondary
Percent Change From Baseline in BMD at the Total Hip at Month 12
Total hip bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 12
Population: Primary efficacy analysis subset, which includes all randomized participants who had a baseline DXA BMD measurement and at least 1 post-baseline DXA BMD measurement at the total hip; LOCF imputation was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in BMD at the Total Hip at Month 12 | -0.5 percent change | Standard Error 0.3 |
| Romosozumab 210 mg | Percent Change From Baseline in BMD at the Total Hip at Month 12 | 2.5 percent change | Standard Error 0.2 |
p-value: <0.000195% CI: [2.3, 3.7]ANCOVA
Secondary
Percent Change From Baseline in BMD at the Total Hip at Month 6
Bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 6
Population: Primary efficacy analysis subset with available data at baseline and month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in BMD at the Total Hip at Month 6 | 0.2 percent change | Standard Error 0.2 |
| Romosozumab 210 mg | Percent Change From Baseline in BMD at the Total Hip at Month 6 | 1.6 percent change | Standard Error 0.2 |
p-value: <0.000195% CI: [0.8, 2]ANCOVA
Secondary
Percent Change From Baseline in Lumbar Spine BMD at Month 6
Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.
Time frame: Baseline and month 6
Population: Primary efficacy analysis subset with available data at baseline and month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Lumbar Spine BMD at Month 6 | 0.3 percent change | Standard Error 0.4 |
| Romosozumab 210 mg | Percent Change From Baseline in Lumbar Spine BMD at Month 6 | 9.0 percent change | Standard Error 0.4 |
p-value: <0.000195% CI: [7.6, 9.7]ANCOVA