Osteoporosis
Conditions
Keywords
osteoporosis, postmenopausal, bone loss
Brief summary
The purpose of this study is to determine whether BA058 is effective in building bone in postmenopausal women with osteoporosis.
Detailed description
This is a randomized, parallel-group, multi-center, dose-finding study to evaluate the effects of BA058 in the treatment of otherwise healthy postmenopausal women with osteoporosis.
Interventions
DRUGteriparatide
teriparatide 20 µg subcutaneous daily
DRUGPlacebo
Placebo subcutaneous daily
DRUGBA058 20 µg
BA058 20 µg subcutaneous daily
DRUGBA058 40 µg
BA058 40 µg subcutaneous daily
DRUGBA058 80 µg
BA058 80 µg subcutaneous daily
Sponsors
Radius Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Primary Inclusion Criteria: * The patient has a bone mineral density T-score ≤ 2.5 at the lumbar spine or hip (femoral neck) by dual energy x-ray absorptiometry (DXA). Women with a bone mineral density T-score of 2.0 or lower and a prior low-trauma forearm, humerus, vertebral, sacral, pelvic, hip, femoral, or tibial fracture within the past 5 years, or who have an additional risk factor such as age 65 or greater or a strong maternal history of osteoporosis defined as a fracture related to osteoporosis or osteoporosis itself as determined by BMD criteria, are also study candidates. * The patient is in good general health as determined by medical history and physical examination and is without evidence of clinically significant abnormality in the opinion of the Investigator. Primary
Exclusion criteria
* History of bone disorders (e.g., Paget's disease) other than postmenopausal osteoporosis. * Prior treatment with approved or as yet unapproved bone-acting investigational agents. * History of carcinoma, nephrolithiasis or urolithiasis within the past five years or osteosarcoma at any time. * History of radiotherapy (radiation therapy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Marker of Bone Metabolism, PINP | 6 months | PINP, N-terminal propeptide of type I procollagen, is a marker of anabolic bone growth. |
| Change in Bone Mineral Density, Total Spine. | 6 months | Total analyzable spine bone mineral density (BMD) was analyzed by DXA at Week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bone Mineral Density, Femoral Neck. | 6 months | Femoral neck bone mineral density (BMD) was analyzed by DXA at Week 24. |
| Change in Bone Mineral Density, Total Hip. | 6 months | Total analyzable hip bone mineral density (BMD) was analyzed by DXA at Week 24. |
| Change in Bone Mineral Density, Total Spine. | 12 months | Total analyzable spine bone mineral density (BMD) was analyzed by DXA at Week 48. |
Countries
United States
Participant flow
Recruitment details
Recruitment for the study started in the US, in January 2007. For the initial 24-week treatment period, patients were randomized to study treatment at 30 study centers in the US, Argentina, India and the UK . Eleven of the 30 study centers treated patients in the 24-week treatment extension period in the US, Argentina, and India.
Pre-assignment details
After eligibility was established, patients entered a 4-week Pretreatment Period during which they received daily Calcium and Vitamin D supplements, were trained in self-injection with the pen devices, and were assessed for additional evaluations at the end of the Pretreatment Period. Patients who remained eligible were randomized on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Placebo | 46 |
| BA058 20 µg | 43 |
| BA058 40 µg | 43 |
| BA058 80 µg | 45 |
| Teriparatide | 45 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Extended 24 Weeks of Treatment | Adverse Event | 0 | 0 | 1 | 1 | 0 |
| Extended 24 Weeks of Treatment | Other | 1 | 1 | 0 | 0 | 1 |
| Extended 24 Weeks of Treatment | Protocol Violation | 0 | 0 | 1 | 0 | 0 |
| Extended 24 Weeks of Treatment | Refusal of treatment | 0 | 1 | 0 | 0 | 0 |
| Initial 24 Weeks | Administrative reasons | 0 | 0 | 1 | 1 | 0 |
| Initial 24 Weeks | Adverse Event | 0 | 1 | 1 | 3 | 2 |
| Initial 24 Weeks | Inability to complete procedures | 0 | 3 | 2 | 1 | 2 |
| Initial 24 Weeks | Lost to Follow-up | 2 | 2 | 1 | 0 | 0 |
| Initial 24 Weeks | Non-compliance | 0 | 0 | 0 | 1 | 1 |
| Initial 24 Weeks | Other | 0 | 2 | 1 | 0 | 0 |
| Initial 24 Weeks | Protocol Violation | 0 | 0 | 0 | 1 | 0 |
| Initial 24 Weeks | Refusal of treatment | 2 | 2 | 1 | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo | BA058 20 µg | BA058 40 µg | BA058 80 µg | Teriparatide | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 7.11 | 66.3 years STANDARD_DEVIATION 6.96 | 64.5 years STANDARD_DEVIATION 7.35 | 64.8 years STANDARD_DEVIATION 7.21 | 64.5 years STANDARD_DEVIATION 7.48 | 65 years STANDARD_DEVIATION 7.19 |
| Sex: Female, Male Female | 46 Participants | 43 Participants | 43 Participants | 45 Participants | 45 Participants | 222 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 45 | 31 / 43 | 32 / 43 | 33 / 45 | 35 / 45 |
| serious Total, serious adverse events | 1 / 45 | 2 / 43 | 0 / 43 | 2 / 45 | 0 / 45 |
Outcome results
Primary
Change in Bone Mineral Density, Total Spine.
Total analyzable spine bone mineral density (BMD) was analyzed by DXA at Week 24.
Time frame: 6 months
Population: The intent to treat (ITT) population included any patient who received at least one dose of study medication; N=221. 187 of the 221 ITT patients had data available for analysis at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Bone Mineral Density, Total Spine. | 1.22 Percent change from baseline | Standard Deviation 3.211 |
| BA058 20 µg | Change in Bone Mineral Density, Total Spine. | 3.30 Percent change from baseline | Standard Deviation 2.068 |
| BA058 40 µg | Change in Bone Mineral Density, Total Spine. | 5.21 Percent change from baseline | Standard Deviation 4.427 |
| BA058 80 µg | Change in Bone Mineral Density, Total Spine. | 6.11 Percent change from baseline | Standard Deviation 3.744 |
| Teriparatide | Change in Bone Mineral Density, Total Spine. | 5.47 Percent change from baseline | Standard Deviation 4.218 |
Comparison: For the BMD endpoint, the planned study size has 80 percent power with alpha=0.02 to detect a difference in mean change from baseline of 3.0 (percent) in BMD for the BA058 group and the BA058 Placebo group using an assumed SD of 3.5-4.0. The estimates for SD are based upon results of lumbar spine BMD presented by Body 2002.p-value: <0.001ANOVA
Comparison: For the BMD endpoint, the planned study size has 80 percent power with alpha=0.02 to detect a difference in mean change from baseline of 3.0 (percent) in BMD for the BA058 group and the BA058 Placebo group using an assumed SD of 3.5-4.0. The estimates for SD are based upon results of lumbar spine BMD presented by Body 2002.p-value: <0.001ANOVA
Primary
Change in Marker of Bone Metabolism, PINP
PINP, N-terminal propeptide of type I procollagen, is a marker of anabolic bone growth.
Time frame: 6 months
Population: The intent to treat (ITT) population included any patient who received at least one dose of study medication; N=221. 193 of the 221 ITT patients had data available for analysis at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Marker of Bone Metabolism, PINP | -13.1 Percent change from baseline | Standard Deviation 26.47 |
| BA058 20 µg | Change in Marker of Bone Metabolism, PINP | 20.0 Percent change from baseline | Standard Deviation 61.05 |
| BA058 40 µg | Change in Marker of Bone Metabolism, PINP | 90.8 Percent change from baseline | Standard Deviation 116.92 |
| BA058 80 µg | Change in Marker of Bone Metabolism, PINP | 97.2 Percent change from baseline | Standard Deviation 123.88 |
| Teriparatide | Change in Marker of Bone Metabolism, PINP | 154.3 Percent change from baseline | Standard Deviation 213.07 |
Comparison: Study size provided 95 percent power to detect a difference in means of 114 (ng/mL) for PINP endpoint between BA058 (SD=147.5) and placebo (SD=34.5). Study size was based on Bauer 2006 data and utilized a 2-tailed 2-sample t-test with a significance level of alpha=0.01 with a Bonferonni adjustment for multiple testing. It included a 10 percent adjustment for within study dropouts over 6 months and a 15 percent adjustment to maintain adequate power for a per protocol analysis of key endpoints.p-value: <0.001ANOVA
Comparison: Study size provided 95 percent power to detect a difference in means of 114 (ng/mL) for PINP endpoint between BA058 (SD=147.5) and placebo (SD=34.5). Study size was based on Bauer 2006 data and utilized a 2-tailed 2-sample t-test with a significance level of alpha=0.01 with a Bonferonni adjustment for multiple testing. It included a 10 percent adjustment for within study dropouts over 6 months and a 15 percent adjustment to maintain adequate power for a per protocol analysis of key endpoints.p-value: <0.001ANOVA
Secondary
Change in Bone Mineral Density, Femoral Neck.
Femoral neck bone mineral density (BMD) was analyzed by DXA at Week 24.
Time frame: 6 months
Population: The intent to treat (ITT) population included any patient who received at least one dose of study medication; N=221. 182 of the 221 ITT patients had data available for analysis at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Bone Mineral Density, Femoral Neck. | 0.79 Percent change from baseline | Standard Deviation 4.797 |
| BA058 20 µg | Change in Bone Mineral Density, Femoral Neck. | 2.69 Percent change from baseline | Standard Deviation 4.022 |
| BA058 40 µg | Change in Bone Mineral Density, Femoral Neck. | 2.20 Percent change from baseline | Standard Deviation 4.406 |
| BA058 80 µg | Change in Bone Mineral Density, Femoral Neck. | 3.07 Percent change from baseline | Standard Deviation 4.175 |
| Teriparatide | Change in Bone Mineral Density, Femoral Neck. | 1.07 Percent change from baseline | Standard Deviation 4.564 |
Secondary
Change in Bone Mineral Density, Total Hip.
Total analyzable hip bone mineral density (BMD) was analyzed by DXA at Week 24.
Time frame: 6 months
Population: The intent to treat (ITT) population included any patient who received at least one dose of study medication; N=221. 182 of the 221 ITT patients had data available for analysis at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Bone Mineral Density, Total Hip. | 0.39 Percent change from baseline | Standard Deviation 3.053 |
| BA058 20 µg | Change in Bone Mineral Density, Total Hip. | 1.43 Percent change from baseline | Standard Deviation 2.639 |
| BA058 40 µg | Change in Bone Mineral Density, Total Hip. | 1.97 Percent change from baseline | Standard Deviation 3.699 |
| BA058 80 µg | Change in Bone Mineral Density, Total Hip. | 2.60 Percent change from baseline | Standard Deviation 3.488 |
| Teriparatide | Change in Bone Mineral Density, Total Hip. | 0.45 Percent change from baseline | Standard Deviation 3.925 |
Secondary
Change in Bone Mineral Density, Total Spine.
Total analyzable spine bone mineral density (BMD) was analyzed by DXA at Week 48.
Time frame: 12 months
Population: The extension population included any patient who continued in the extended 24 weeks of treatment; N=55. 49 of the 55 extension patients had data available for analysis at Week 48.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Bone Mineral Density, Total Spine. | 0.74 Percent change from baseline | Standard Deviation 3.541 |
| BA058 20 µg | Change in Bone Mineral Density, Total Spine. | 5.14 Percent change from baseline | Standard Deviation 3.164 |
| BA058 40 µg | Change in Bone Mineral Density, Total Spine. | 9.84 Percent change from baseline | Standard Deviation 5.313 |
| BA058 80 µg | Change in Bone Mineral Density, Total Spine. | 12.94 Percent change from baseline | Standard Deviation 3.251 |
| Teriparatide | Change in Bone Mineral Density, Total Spine. | 8.63 Percent change from baseline | Standard Deviation 6.8 |