Low Bone Mineral Density
Conditions
Keywords
bone loss, osteoporosis
Brief summary
An Open-label, Single-arm Extension Study to Evaluate the Long-term Safety of Denosumab Administration in Postmenopausal Women with Low Bone Mineral Density
Interventions
DRUGAMG 162
AMG 162; 60 mg/mL of Denosumab given to all subjects at Screening/Day 1, Month 6, Month 12, Month 18, Month 24, Month 30, Month 36 and Month 42
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Subject must be ambulatory * Subject must have atteneded the 20010223 end-of-study visit and have completed all tests and procedures during the end-of-study visit * signed informed consent must be obtained before any study-specific procedures
Exclusion criteria
* Experienced severe and/or serious adverse event which were thought to be related to denosumab administration during the 20010223 study. * Developed grade 3 or 4 laboratory abnormalities based on Common Terminology Criteria for Adverse Events v3.0 during the 20010223 study which did not normalized upon follow up or did not have diagnosis or treatment. * Newly diagnosed conditions such as hyper/hypo thyroidism, rheumatoid arthritis, other bone diseases, renal disease. * Using therapies while participating in the 20010223 study such as oral bisphosphonates, calcitonin, oral strontium, SERMS, systemic glucocortiocosteriods.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Lumbar Spine Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 8 years |
| Total Hip Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 8 years |
| Distal 1/3 Radius Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 8 years |
Secondary
| Measure | Time frame |
|---|---|
| Bone-Specific Alkaline Phosphatase Percent Change From Parent Study 20010223 Baseline to Year 8 | 8 years |
| Serum C-Telopeptide Percent Change From Parent Study 20010223 Baseline to Year 8 | 8 years |
Participant flow
Recruitment details
Subjects who successfully completed the double-blind, randomized, 4-year dose-ranging parent study 20010223
Participants by arm
| Arm | Count |
|---|---|
| Placebo In the parent study 20010223, this cohort received placebo SC for 4 years. Treatment for 4 years in the current study represents initial exposure to denosumab 60 mg Q6M. | 23 |
| Denosumab 210 mg Q6M In the parent study 20010223, this cohort received denosumab 210 mg SC Q6M for 2 years and placebo Q6M for 2 years. These subjects were retreated with denosumab 60mg Q6M for 4 years in the current study. | 17 |
| Denosumab 30 mg Q3M In the parent study 20010223, this cohort received denosumab 30 mg SC Q3M for 2 years, placebo Q6M for 1 year, followed by denosumab 60 mg Q6M for 1 year. These subjects were treated with denosumab 60 mg Q6M for 4 years in the current study. | 14 |
| Denosumab Continuous Treatment In the parent study 20010223, this cohort received denosumab SC for 4 years. During the first 2 years, the doses were 6 mg Q3M, 14 mg Q3M, 14 mg Q6M, 60 mg Q6M, or 100 mg Q6M. During the last two years, all subjects received 60 mg Q6M. Treatment for 4 years in the current study represents 8 years of continuous exposure to denosumab for this cohort. | 124 |
| Alendronate 70mg QW In the parent study, this cohort received alendronate 70 mg orally (PO) QW for 2 years; treatment was discontinued for the remaining 2 years of parent Study 20010223. Treatment for 4 year in the current study represents initial exposure to denosumab in subjects previously treated with alendronate. | 22 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 5 | 1 |
| Overall Study | Death | 2 | 0 | 2 | 4 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 2 | 2 |
| Overall Study | Physician Decision | 1 | 1 | 0 | 1 | 0 |
| Overall Study | site closure etc | 4 | 2 | 1 | 8 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 0 | 14 | 4 |
Baseline characteristics
| Characteristic | Denosumab 210 mg Q6M | Total | Alendronate 70mg QW | Placebo | Denosumab Continuous Treatment | Denosumab 30 mg Q3M |
|---|---|---|---|---|---|---|
| Age, Continuous | 65.8 Years STANDARD_DEVIATION 9.4 | 66.1 Years STANDARD_DEVIATION 7.7 | 66.6 Years STANDARD_DEVIATION 8.9 | 65.8 Years STANDARD_DEVIATION 9.1 | 65.8 Years STANDARD_DEVIATION 7 | 68.0 Years STANDARD_DEVIATION 7.2 |
| Baseline Bone Mineral Density T-score of Each Anatomic Site Distal 1/3 radius T-score | -1.45 T-score STANDARD_DEVIATION 0.98 | -1.35 T-score STANDARD_DEVIATION 1.19 | -1.57 T-score STANDARD_DEVIATION 0.98 | -1.91 T-score STANDARD_DEVIATION 1.25 | -1.23 T-score STANDARD_DEVIATION 1.21 | -1.14 T-score STANDARD_DEVIATION 1.29 |
| Baseline Bone Mineral Density T-score of Each Anatomic Site Lumbar spine BMD T-score | -2.02 T-score STANDARD_DEVIATION 1.16 | -1.55 T-score STANDARD_DEVIATION 0.96 | -1.64 T-score STANDARD_DEVIATION 1.09 | -2.36 T-score STANDARD_DEVIATION 0.62 | -1.35 T-score STANDARD_DEVIATION 0.87 | -1.29 T-score STANDARD_DEVIATION 0.94 |
| Baseline Bone Mineral Density T-score of Each Anatomic Site Total hip BMD T-score | -1.39 T-score STANDARD_DEVIATION 0.67 | -1.21 T-score STANDARD_DEVIATION 0.73 | -1.50 T-score STANDARD_DEVIATION 0.81 | -1.63 T-score STANDARD_DEVIATION 0.75 | -1.08 T-score STANDARD_DEVIATION 0.68 | -1.05 T-score STANDARD_DEVIATION 0.75 |
| Race/Ethnicity, Customized Aborigine | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 17 Participants | 2 Participants | 5 Participants | 8 Participants | 1 Participants |
| Race/Ethnicity, Customized Japanese | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White or Caucasian | 16 Participants | 178 Participants | 20 Participants | 18 Participants | 112 Participants | 12 Participants |
| Sex: Female, Male Female | 17 Participants | 200 Participants | 22 Participants | 23 Participants | 124 Participants | 14 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 23 | 15 / 17 | 13 / 14 | 106 / 124 | 19 / 22 | 171 / 200 |
| serious Total, serious adverse events | 3 / 23 | 3 / 17 | 5 / 14 | 31 / 124 | 3 / 22 | 45 / 200 |
Outcome results
Primary
Distal 1/3 Radius Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8
Time frame: 8 years
Population: Subjects with nonmissing value at parent study 20010223 baseline and Year 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Distal 1/3 Radius Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | -5.2 percent |
| Denosumab 210 mg Q6M | Distal 1/3 Radius Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 1.4 percent |
| Denosumab 30 mg Q3M | Distal 1/3 Radius Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 0.6 percent |
| Denosumab Continuous Treatment | Distal 1/3 Radius Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 1.3 percent |
| Alendronate 70mg QW | Distal 1/3 Radius Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | -2.2 percent |
Primary
Lumbar Spine Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8
Time frame: 8 years
Population: Subjects with nonmissing value at parent study 20010223 baseline and Year 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Lumbar Spine Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 8.4 percent |
| Denosumab 210 mg Q6M | Lumbar Spine Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 11.2 percent |
| Denosumab 30 mg Q3M | Lumbar Spine Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 11.0 percent |
| Denosumab Continuous Treatment | Lumbar Spine Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 16.5 percent |
| Alendronate 70mg QW | Lumbar Spine Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 12.4 percent |
Primary
Total Hip Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8
Time frame: 8 years
Population: Subjects with nonmissing value at parent study 20010223 baseline and Year 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Total Hip Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 1.1 percent |
| Denosumab 210 mg Q6M | Total Hip Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 4.3 percent |
| Denosumab 30 mg Q3M | Total Hip Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 2.3 percent |
| Denosumab Continuous Treatment | Total Hip Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 6.8 percent |
| Alendronate 70mg QW | Total Hip Bone Mineral Density Percent Change From Parent Study 20010223 Baseline to Year 8 | 3.4 percent |
Secondary
Bone-Specific Alkaline Phosphatase Percent Change From Parent Study 20010223 Baseline to Year 8
Time frame: 8 years
Population: Subjects with nonmissing value at parent study 20010223 baseline and Year 8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Bone-Specific Alkaline Phosphatase Percent Change From Parent Study 20010223 Baseline to Year 8 | -55.8 percent |
| Denosumab 210 mg Q6M | Bone-Specific Alkaline Phosphatase Percent Change From Parent Study 20010223 Baseline to Year 8 | -44.7 percent |
| Denosumab 30 mg Q3M | Bone-Specific Alkaline Phosphatase Percent Change From Parent Study 20010223 Baseline to Year 8 | -52.5 percent |
| Denosumab Continuous Treatment | Bone-Specific Alkaline Phosphatase Percent Change From Parent Study 20010223 Baseline to Year 8 | -44.4 percent |
| Alendronate 70mg QW | Bone-Specific Alkaline Phosphatase Percent Change From Parent Study 20010223 Baseline to Year 8 | -54.2 percent |
Secondary
Serum C-Telopeptide Percent Change From Parent Study 20010223 Baseline to Year 8
Time frame: 8 years
Population: Subjects with nonmissing value at parent study 20010223 baseline and Year 8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Serum C-Telopeptide Percent Change From Parent Study 20010223 Baseline to Year 8 | -66.4 percent |
| Denosumab 210 mg Q6M | Serum C-Telopeptide Percent Change From Parent Study 20010223 Baseline to Year 8 | -72.0 percent |
| Denosumab 30 mg Q3M | Serum C-Telopeptide Percent Change From Parent Study 20010223 Baseline to Year 8 | -48.0 percent |
| Denosumab Continuous Treatment | Serum C-Telopeptide Percent Change From Parent Study 20010223 Baseline to Year 8 | -64.6 percent |
| Alendronate 70mg QW | Serum C-Telopeptide Percent Change From Parent Study 20010223 Baseline to Year 8 | -49.8 percent |