Postmenopausal Osteoporosis
Conditions
Keywords
Osteoporosis, transdermal delivery, microneedle, solid microstructured transdermal system, abaloparatide-sMTS, patch, abaloparatide, fracture, bone loss, TYMLOS®
Brief summary
A 12-month study to compare the efficacy and safety of abaloparatide-solid microstructured transdermal system (sMTS) with abaloparatide-subcutaneous (SC).
Detailed description
This study aims to evaluate the non-inferiority of abaloparatide-sMTS 300 micrograms (mcg) compared to abaloparatide-SC 80 mcg based on lumbar spine bone mineral density (BMD) at 12 months and to evaluate the safety and tolerability of abaloparatide-sMTS in the treatment of postmenopausal women with osteoporosis.
Interventions
COMBINATION_PRODUCTabaloparatide
Abaloparatide is a synthetic peptide that is a potent and selective activator of the parathyroid hormone 1 receptor signaling pathway.
COMBINATION_PRODUCTabaloparatide solid microstructured transdermal system
Abaloparatide-sMTS is a drug-device combination product consisting of the drug abaloparatide coated onto a sMTS array for transdermal administration of abaloparatide.
Sponsors
Radius Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Healthy ambulatory female from 50 to 85 years of age (inclusive) with postmenopausal osteoporosis * Participants who are 50 to 65 years old with BMD T-score ≤ -2.5 and \> -5.0 at the lumbar spine or hip (femoral neck or total hip) by dual energy x-ray absorptiometry (DXA) and meet one of the following: 1) radiological evidence of 2 or more mild or one or more moderate lumbar or thoracic vertebral fractures or 2) history of fragility fracture to the forearm, humerus, sacrum, pelvis, hip, femur, or tibia within the past 5 years. * Participants older than 65 years with BMD T score ≤ -2.0 and \> -5.0 who meet the fracture criteria may be enrolled * Participants older than 65 years with BMD T score ≤ -3.0 and \> -5.0 at the lumbar spine or hip (femoral neck or total hip) by DXA * Body mass index of 18.5 to 33 kilograms (kg)/square meters (m\^2), inclusive * serum calcium (albumin-corrected), parathyroid hormone (1-84), serum phosphorus, alkaline phosphatase, and thyroid stimulating hormone within the normal reference range * Serum 25-hydroxyvitamin D values must be ≥ 20 nanograms (ng)/milliliters (mL)
Exclusion criteria
* History of more than 4 mild or moderate spine fractures or any severe fracture * Abnormality of the spine or hip that would prohibit assessment of BMD * History of bone disorders other than postmenopausal osteoporosis or a diagnosis of cancer within the last 5 years * History of Cushing's disease, thyroid, parathyroid, or malabsorptive syndromes or any chronic or recurrent diseases or disturbances that would interfere with the interpretation of study data or compromise the safety of the patient * Prior treatment with parathyroid hormone, parathyroid hormone-related peptide-derived drugs, or bone anabolic steroids, including abaloparatide, teriparatide, or parathyroid hormone (1-84) * Prior treatment with intravenous (IV) bisphosphonates at any time or oral bisphosphonates within the past 3 years; fluoride or strontium within the past 5 years; treatment with corticosteroids within the past 12 months; or selective estrogen receptor modulators within the past 6 months (except hormone replacement therapy) * Prior treatment with an investigational drug or device within the past 90 days or 5 half-lives of the investigational drug, whichever is longer * History of nephrolithiasis or urolithiasis within the past 5 years or hereditary disorders predisposing to osteosarcoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lumbar Spine BMD at Month 12 | Baseline, Month 12 | Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Hip BMD at Month 12 | Baseline, Month 12 | Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. |
| Percent Change From Baseline in Femoral Neck BMD at Month 12 | Baseline, Month 12 | Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. |
Countries
Denmark, Hungary, Poland, Puerto Rico, United States
Participant flow
Recruitment details
Eligible female participants were randomized to a 12-month open-label study treatment at 83 study centers in the United States, Denmark, Hungary, and Poland.
Participants by arm
| Arm | Count |
|---|---|
| Abaloparatide-SC Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen. | 255 |
| Abaloparatide-sMTS Participants self-administered daily doses of abaloparatide-sMTS 300 mcg. | 256 |
| Total | 511 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 29 | 19 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 5 | 2 |
| Overall Study | Other than Specified | 4 | 1 |
| Overall Study | Protocol Deviation | 0 | 2 |
| Overall Study | Significant Deterioration from Baseline (≥7%) of Bone Mineral Density (BMD) at Spine or Hip | 0 | 2 |
| Overall Study | Withdrawal by Subject | 25 | 29 |
Baseline characteristics
| Characteristic | Abaloparatide-SC | Abaloparatide-sMTS | Total |
|---|---|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 6.87 | 69.3 years STANDARD_DEVIATION 6.49 | 69.1 years STANDARD_DEVIATION 6.68 |
| Lumbar Spine BMD T-Score | -2.569 BMD T-Score STANDARD_DEVIATION 1.1534 | -2.554 BMD T-Score STANDARD_DEVIATION 1.0997 | -2.562 BMD T-Score STANDARD_DEVIATION 1.1257 |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 27 Participants | 24 Participants | 51 Participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 227 Participants | 230 Participants | 457 Participants |
| Race/Ethnicity, Customized Ethnicity: Unknown | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Race: American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race: Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Race: Multiple | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race: Other | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 248 Participants | 243 Participants | 491 Participants |
| Sex: Female, Male Female | 255 Participants | 256 Participants | 511 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 | 1 / 254 | 0 / 252 |
| other Total, other adverse events | 204 / 254 | 239 / 252 |
| serious Total, serious adverse events | 19 / 254 | 16 / 252 |
Outcome results
Primary
Percent Change From Baseline in Lumbar Spine BMD at Month 12
Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory.
Time frame: Baseline, Month 12
Population: Modified Intention-to-Treat (mITT): All randomized participants who received at least 1 dose of study drug and had a baseline lumbar spine BMD measurement and at least 1 postbaseline lumbar spine BMD measurement. Overall number of participants analyzed = participants with valid assessments at both baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide-SC | Percent Change From Baseline in Lumbar Spine BMD at Month 12 | 10.8571 percent change | Standard Error 0.4755 |
| Abaloparatide-sMTS | Percent Change From Baseline in Lumbar Spine BMD at Month 12 | 7.1361 percent change | Standard Error 0.4605 |
95% CI: [-5.0089, -2.4331]
Secondary
Percent Change From Baseline in Femoral Neck BMD at Month 12
Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory.
Time frame: Baseline, Month 12
Population: mITT: All randomized participants who received at least 1 dose of study drug and had a baseline lumbar spine BMD measurement and at least 1 postbaseline lumbar spine BMD measurement. Overall number of participants analyzed = participants with valid assessments at both baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide-SC | Percent Change From Baseline in Femoral Neck BMD at Month 12 | 3.4159 percent change | Standard Error 0.375 |
| Abaloparatide-sMTS | Percent Change From Baseline in Femoral Neck BMD at Month 12 | 1.9163 percent change | Standard Error 0.3599 |
Secondary
Percent Change From Baseline in Total Hip BMD at Month 12
Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory.
Time frame: Baseline, Month 12
Population: mITT: All randomized participants who received at least 1 dose of study drug and had a baseline lumbar spine BMD measurement and at least 1 postbaseline lumbar spine BMD measurement. Overall number of participants analyzed = participants with valid assessments at both baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide-SC | Percent Change From Baseline in Total Hip BMD at Month 12 | 3.6995 percent change | Standard Error 0.2776 |
| Abaloparatide-sMTS | Percent Change From Baseline in Total Hip BMD at Month 12 | 1.9688 percent change | Standard Error 0.2675 |