Postmenopausal Osteoporosis
Conditions
Keywords
postmenopausal osteoporosis, osteoporosis, postmenopausal, denosumab, women
Brief summary
This study will compare the effect of denosumab produced by two different manufacturing processes on bone mineral density at the lumbar spine in postmenopausal women with osteoporosis.
Interventions
DRUGDenosumab (CP2)
Denosumab produced by a process referred to as CP2, administered subcutaneously from a prefilled syringe.
DRUGDenosumab (CP4)
Denosumab produced by a process referred to as CP4, administered subcutaneously from a prefilled syringe.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to any study-specific activities/procedures * Ambulatory postmenopausal women. * Age 55 years or older * Screening BMD value equivalent to a T-score less than or equal to -2.5 at the lumbar spine, total hip, or femoral neck.
Exclusion criteria
* Administration of osteoporosis treatments or bone active treatments within specific timeframes * Vitamin D deficiency * Diseases and conditions that affect bone metabolism (e.g., hypo/hyper-parathyroidism; hypo/hyperthyroidism, unless stable and well-controlled) * Contraindications to denosumab therapy (e.g., hypocalcemia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine BMD | 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 |
|---|---|
| Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) | Baseline, month 1, month 6 and month 12 |
| Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Baseline, month 1, month 6 and month 12 |
Countries
Canada, Denmark, Poland, United States
Participant flow
Recruitment details
This study was conducted at 21 centers in Poland, Denmark, United States (US), and Canada. The first participant enrolled on 05 May 2014 and the last participant enrolled on 03 July 2014.
Pre-assignment details
Ambulatory postmenopausal women 55 years or older with a bone mineral density (BMD) equivalent to a T-score of ≤ 2.5 at lumbar spine, total hip, or femoral neck were eligible to enroll. Five hundred and forty-seven women were screened; 394 were enrolled and 153 did not meet eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| Denosumab CP2 Participants received 60 mg denosumab manufactured using the current CP2 process subcutaneously once every 6 months for 1 year. | 197 |
| Denosumab CP4 Participants received 60 mg denosumab manufactured using the new CP4 process subcutaneously once every 6 months for 1 year. | 197 |
| Total | 394 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Decision by Sponsor | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Protocol Specified Criteria | 2 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Denosumab CP2 | Denosumab CP4 | Total |
|---|---|---|---|
| Age, Continuous | 68.0 years STANDARD_DEVIATION 6.8 | 68.3 years STANDARD_DEVIATION 7.3 | 68.1 years STANDARD_DEVIATION 7 |
| Age, Customized < 65 years | 65 participants | 70 participants | 135 participants |
| Age, Customized ≥ 65 years | 132 participants | 127 participants | 259 participants |
| Lumbar Spine Bone Mineral Density (BMD) Score | -2.75 T-score STANDARD_DEVIATION 0.91 | -2.75 T-score STANDARD_DEVIATION 0.75 | -2.75 T-score STANDARD_DEVIATION 0.83 |
| Race/Ethnicity, Customized Asian | 4 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 190 participants | 195 participants | 385 participants |
| Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | 56.6 μg/L | 61.5 μg/L | 59.3 μg/L |
| Serum Type I Collagen C-telopeptide (CTX-1) | 0.433 ng/mL | 0.462 ng/mL | 0.452 ng/mL |
| Sex: Female, Male Female | 197 Participants | 197 Participants | 394 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 | 25 / 196 | 36 / 196 |
| serious Total, serious adverse events | 13 / 196 | 6 / 196 |
Outcome results
Primary
Percent Change From Baseline in Lumbar Spine BMD
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: The primary efficacy analysis subset included all randomized participants who had a baseline lumbar spine DXA BMD measurement and at least 1 postbaseline lumbar spine DXA BMD measurement. Postbaseline BMD values obtained at the early termination visit were carried forward as the month-12 value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Denosumab CP2 | Percent Change From Baseline in Lumbar Spine BMD | 5.78 percent change | Standard Deviation 3.44 |
| Denosumab CP4 | Percent Change From Baseline in Lumbar Spine BMD | 5.73 percent change | Standard Deviation 3.08 |
Comparison: The treatment comparison was analyzed using the analysis of covariance (ANCOVA) model including treatment, baseline BMD value, machine type, and machine type-by-baseline BMD value interaction. The effect of denosumab CP4 on lumbar spine BMD at 12 months relative to the effect of denosumab CP2 was estimated by the least-squares mean of the treatment difference (denosumab CP4 - denosumab CP2) and the corresponding 2-sided 95% confidence interval (CI).p-value: <0.00195% CI: [-0.72, 0.57]ANCOVA
Comparison: The treatment comparison was analyzed using the analysis of covariance (ANCOVA) model including treatment, baseline BMD value, machine type, and machine type-by-baseline BMD value interaction. The effect of denosumab CP4 on lumbar spine BMD at 12 months relative to the effect of denosumab CP2 was estimated by the least-squares mean of the treatment difference (denosumab CP4 - denosumab CP2) and the corresponding 2-sided 95% confidence interval (CI).p-value: <0.00195% CI: [-0.72, 0.57]ANCOVA
Secondary
Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP)
Time frame: Baseline, month 1, month 6 and month 12
Population: The bone turnover marker (BTM) efficacy analysis subset includes all randomized participants who had a baseline measurement and at least one post baseline measurement. n indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Denosumab CP2 | Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Month 1 (n = 195, 193) | -29.59 percent change |
| Denosumab CP2 | Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Month 6 (n = 192, 190) | -76.63 percent change |
| Denosumab CP2 | Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Month 12 (n = 186, 188) | -71.44 percent change |
| Denosumab CP4 | Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Month 1 (n = 195, 193) | -29.86 percent change |
| Denosumab CP4 | Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Month 6 (n = 192, 190) | -77.74 percent change |
| Denosumab CP4 | Percent Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (P1NP) | Month 12 (n = 186, 188) | -72.08 percent change |
Secondary
Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX)
Time frame: Baseline, month 1, month 6 and month 12
Population: The bone turnover marker (BTM) efficacy analysis subset includes all randomized participants who had a baseline measurement and at least one post baseline measurement. n indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Denosumab CP2 | Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) | Month 1 (n = 195, 193) | -86.39 percent change |
| Denosumab CP2 | Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) | Month 6 (n = 191, 189) | -76.46 percent change |
| Denosumab CP2 | Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) | Month 12 (n = 187, 188) | -71.34 percent change |
| Denosumab CP4 | Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) | Month 1 (n = 195, 193) | -88.05 percent change |
| Denosumab CP4 | Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) | Month 6 (n = 191, 189) | -79.48 percent change |
| Denosumab CP4 | Percent Change From Baseline in Serum Type I Collagen C-telopeptide (sCTX) | Month 12 (n = 187, 188) | -75.44 percent change |