Postmenopausal Osteoporosis
Conditions
Keywords
postmenopausal osteoporosis, transdermal delivery, microstructure patch, abaloparatide
Brief summary
This was an open-label, single-center study to evaluate the usability of abaloparatide-sMTS by participants with low BMD.
Detailed description
This study aimed to evaluate the ability of participants to self-administer 300 μg abaloparatide-sMTS over a period of 29 days based on PK and PD markers.
Interventions
COMBINATION_PRODUCTabaloparatide-sMTS
Abaloparatide-sMTS is a drug-device combination product consisting of the drug abaloparatide coated onto an sMTS array for transdermal administration of abaloparatide.
Sponsors
Radius Health, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal for at least 2 years * BMD T-score based on the female reference range \<-1.0 and \>-5.0 at the lumbar spine (L1-L4) or hip (femoral neck or total hip) by dual energy X-ray absorptiometry (DXA) * Good general health as determined by medical history and physical exam (including vital signs, and has a body mass index up to 33 kilograms/square meter (kg/m\^2) * Laboratory tests within the normal range including serum calcium (albumin-corrected), intact parathyroid hormone (PTH), serum phosphorus, alkaline phosphatase, and thyroid stimulating hormone * Serum 25-hydroxyvitamin D values ≥ 20 nanograms per milliliter (ng/mL)
Exclusion criteria
* History of prior external beam or implant radiation therapy involving the skeleton, other than radioiodine * History of bone disorders other than postmenopausal osteoporosis (such as Paget's disease) * History of cancer within the last 5 years (with the exception of basal cell or squamous cancer of the skin) * History of Cushing's disease, hypo or hyperparathyroidism, or malabsorptive syndromes within the past year * Prior treatment with PTH, PTH-related peptide-derived drugs, or bone anabolic steroids, including abaloparatide, teriparatide, or PTH (1-84) * Prior treatment with intravenous bisphosphonates at any time or oral bisphosphonates within the past year (12 months). Participants who have received a short course of oral bisphosphonate therapy (3 months or less) may be enrolled as long as the treatment occurred 6 or more months prior to enrollment * Prior treatment with an investigational drug or device within the past 3 months or 5 half-lives of the investigational drug, whichever is longer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Abaloparatide Maximum Plasma Concentration (Cmax) on Day 29 | 0 (predose), 10 minutes, 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, and 4 hours postdose on Day 29 |
| Abaloparatide Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) on Day 29 | 0 (predose) and 4 hours postdose on Day 29 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline of Serum Procollagen Type I N-Terminal Propeptides (s-PINP) at Day 29 | Baseline, Day 29 | Blood samples were taken to measure s-PINP, a bone formation marker. s-PINP concentrations reflect the rate of skeletal new bone formation. Increases in s-PINP indicate anabolic biologic response in the bone. |
| Change From Baseline of Serum Calcium (Albumin-Corrected) to Predose and Postdose on Day 29 | Baseline, 0 (predose) and 4 hours postdose on Day 29 | — |
| Change From Baseline of Serum Phosphorus to Predose and Postdose on Day 29 | Baseline, 0 (predose) and 4 hours postdose on Day 29 | — |
| Change From Baseline of Cyclic Adenosine Monophosphate (cAMP) to Day 29 | Baseline, 0 (predose) and 30-minutes postdose on Day 29 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abaloparatide-sMTS Abaloparatide-sMTS 300 μg was applied to the thigh for 5 minutes once daily for 29 days. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Abaloparatide-sMTS |
|---|---|
| Age, Continuous | 65.2 years STANDARD_DEVIATION 6.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
Abaloparatide Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) on Day 29
Time frame: 0 (predose) and 4 hours postdose on Day 29
Population: The Pharmacokinetic Analysis Population included all participants who received at least 1 dose of study drug and had sufficient evaluable plasma concentrations to reliably estimate 1 or more PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide-sMTS | Abaloparatide Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) on Day 29 | 604.7 hour*pg/mL | Geometric Coefficient of Variation 51.1 |
Primary
Abaloparatide Maximum Plasma Concentration (Cmax) on Day 29
Time frame: 0 (predose), 10 minutes, 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, and 4 hours postdose on Day 29
Population: The Pharmacokinetic Analysis Population included all participants who received at least 1 dose of study drug and who had sufficient evaluable plasma concentrations to reliably estimate 1 or more PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide-sMTS | Abaloparatide Maximum Plasma Concentration (Cmax) on Day 29 | 399.6 picograms/milliliter (pg/mL) | Geometric Coefficient of Variation 41.8 |
Secondary
Change From Baseline of Cyclic Adenosine Monophosphate (cAMP) to Day 29
Time frame: Baseline, 0 (predose) and 30-minutes postdose on Day 29
Population: The Safety Population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abaloparatide-sMTS | Change From Baseline of Cyclic Adenosine Monophosphate (cAMP) to Day 29 | Day 29, predose | -0.0030 micromoles/liter (μmol/L) | Standard Deviation 0.0023 |
| Abaloparatide-sMTS | Change From Baseline of Cyclic Adenosine Monophosphate (cAMP) to Day 29 | Day 29, postdose | -0.0006 micromoles/liter (μmol/L) | Standard Deviation 0.0046 |
Secondary
Change From Baseline of Serum Calcium (Albumin-Corrected) to Predose and Postdose on Day 29
Time frame: Baseline, 0 (predose) and 4 hours postdose on Day 29
Population: The Safety Population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abaloparatide-sMTS | Change From Baseline of Serum Calcium (Albumin-Corrected) to Predose and Postdose on Day 29 | Day 29, predose | -0.031 millimoles/liter (mmol/L) | Standard Deviation 0.0986 |
| Abaloparatide-sMTS | Change From Baseline of Serum Calcium (Albumin-Corrected) to Predose and Postdose on Day 29 | Day 29, postdose | -0.002 millimoles/liter (mmol/L) | Standard Deviation 0.0659 |
Secondary
Change From Baseline of Serum Phosphorus to Predose and Postdose on Day 29
Time frame: Baseline, 0 (predose) and 4 hours postdose on Day 29
Population: The Safety Population includes all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abaloparatide-sMTS | Change From Baseline of Serum Phosphorus to Predose and Postdose on Day 29 | Day 29, predose | 0.051 mmol/L | Standard Deviation 0.1832 |
| Abaloparatide-sMTS | Change From Baseline of Serum Phosphorus to Predose and Postdose on Day 29 | Day 29, postdose | 0.006 mmol/L | Standard Deviation 0.1877 |
Secondary
Percent Change From Baseline of Serum Procollagen Type I N-Terminal Propeptides (s-PINP) at Day 29
Blood samples were taken to measure s-PINP, a bone formation marker. s-PINP concentrations reflect the rate of skeletal new bone formation. Increases in s-PINP indicate anabolic biologic response in the bone.
Time frame: Baseline, Day 29
Population: The Bone Metabolism Population includes all participants in the Safety Population who have baseline and at least one post-baseline s-PINP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide-sMTS | Percent Change From Baseline of Serum Procollagen Type I N-Terminal Propeptides (s-PINP) at Day 29 | 103.16 percent change | Standard Deviation 104.729 |