Age Related Osteoporosis, Osteoporosis, Osteoporosis, Age-Related, Osteoporosis Localized to Spine, Osteoporosis of Vertebrae, Osteoporosis Senile
Conditions
Keywords
BA058, abaloparatide, abaloparatide-SC, osteoporosis, male osteoporosis, TYMLOS®, fracture, bone loss
Brief summary
A 12-month study to measure the efficacy and safety of abaloparatide in men with osteoporosis.
Detailed description
The primary objective of this prospective controlled study is to evaluate the efficacy and the safety of abaloparatide 80 micrograms (mcg) per day administered subcutaneously (SC) compared to placebo in men with osteoporosis. Efficacy was primarily assessed by the change in bone mineral density (BMD) over 12 months.
Interventions
DRUGAbaloparatide
Abaloparatide is a synthetic peptide that is a potent and selective activator of the parathyroid hormone 1 receptor signaling pathway.
DRUGPlacebo
Abaloparatide-matched placebo.
Sponsors
Radius Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Treatment will be blinded to participants, investigators, outcome Assessor and care provider throughout the study except in a medical emergency where the identity of study medication is necessary to appropriately treat the participant.
Intervention model description
Participants will be randomized in a 2:1 treatment ratio (abaloparatide:placebo).
Eligibility
Sex/Gender
MALE
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Healthy ambulatory male from 40 to 85 years of age (inclusive) with primary osteoporosis or osteoporosis associated with hypogonadism. * The participant has a BMD T-score based on female or male reference range (depending on date of enrollment) as assessed by the central imaging vendor of ≤ -2.5 at the lumbar spine (L1-L4) or hip (femoral neck or total hip) by dual energy X-ray absorptiometry (DXA) or ≤ -1.5 and with radiologic evidence of vertebral fracture or a documented history of low-trauma nonvertebral fracture sustained in the past 5 years. Men older than 65 years may be enrolled if they have a BMD T-score ≤ -2.0 even if they do not meet the fracture criteria. * Normal medical history, physical examination, including vital signs, and body mass index. * Hypogonadal participants whose doses of androgens have been stable for at least twelve months before randomization are eligible and may continue therapy during the study. * Laboratory tests within the normal range including serum calcium (albumin-corrected), parathyroid hormone, serum phosphorus and alkaline phosphatase, and thyroid stimulating hormone values. Key
Exclusion criteria
* Presence of abnormalities of the lumbar spine that would prohibit assessment of spinal BMD, defined as having at least 2 radiologically evaluable vertebrae within L1-L4. * A BMD T-score of ≤-3.5 at the total hip, femoral neck, or lumbar spine based on female or male reference range (depending on date of enrollment). * Unevaluable hip BMD or participants who have undergone bilateral hip replacement. * Fragility fracture within the prior twelve months. * History of severe vertebral fracture or \>2 moderate vertebral fractures. * History of bone disorders (for example, Paget's disease) other than osteoporosis. * participant with clinical signs of hypogonadism present at screening who plan to initiate testosterone replacement. * History of prior external beam or implant radiation therapy involving the skeleton other than radioiodine. * History of chronic or recurrent renal, hepatic, pulmonary, allergic, cardiovascular, gastrointestinal, endocrine, central nervous system, hematologic or metabolic diseases, or immunologic, emotional and/or psychiatric disturbances to a degree that would interfere with the interpretation of study data or compromise the safety of the participant. * History of Cushing's disease, growth hormone deficiency or excess, hyperthyroidism, hypo- or hyperparathyroidism or malabsorptive syndromes within the past year.
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. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. Positive changes from baseline indicate improvement in bone health. |
| Percent Change From Baseline in Lumbar Spine BMD at Month 6 | Baseline, Month 6 | Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health. |
| Percent Change in Total Hip BMD From Baseline at Month 6 | Baseline, Month 6 | Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health. |
| Percent Change From Baseline in Femoral Neck BMD at Month 6 | Baseline, Month 6 | Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health. |
| Percent Change From Baseline in Ultra-Distal Radius BMD at Month 12 | Baseline, Month 12 | Ultra-distal radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health. |
| Percent Change From Baseline in Distal One-third Radius BMD at Month 12 | Baseline, Month 12 | Distal one-third radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health. |
| 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. Positive changes from baseline indicate improvement in bone health. |
| Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Month 12 | Baseline, Month 12 | Blood samples were taken to measure s-CTX. Elevated levels of s-CTX indicate increased bone resorption (bone loss). |
| Number of Participants With New Clinical Fractures | Baseline through Month 12 | Radiological evaluations were performed to identify any new clinical fractures (occurring after the screening visit). |
| Percent of Participants With Change in Disease Status | Baseline through Month 12 | The percentage of participants converting from the categories of osteoporosis to osteopenia or from osteopenia to normal at End of Treatment (Month 12) was assessed. Osteoporosis was defined as lumbar spine or total hip BMD T-score ≤ -2.5. Osteopenia was defined as one of the following: * Lumbar spine \> -2.5 and total hip BMD T-score \> -2.5 and \< -1.0 * Lumbar spine \> -2.5 and \< -1.0 and total hip BMD T-score \> -2.5 * Normal was defined as lumbar spine and total hip BMD T-score ≥ -1.0. |
| Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip | Month 12 | Lumbar spine, femoral neck, and total hip BMD were assessed by DXA scans evaluated by a central imaging laboratory. |
| Percent Change From Baseline in Total Hip Volumetric BMD as Measured by Quantitative Computed Tomography (QCT) at Month 12 | Baseline, Month 12 | QCT scans were evaluated by a central imaging laboratory. |
| Percent Change From Baseline in Femoral Neck Volumetric BMD as Measured by QCT at Month 12 | Baseline, Month 12 | QCT scans were evaluated by a central imaging laboratory. |
| Percent Change From Baseline in Serum Procollagen Type I N-terminal Propeptide (s-PINP) at Month 12 | Baseline, Month 12 | 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. |
Countries
Italy, Poland, United States
Participant flow
Pre-assignment details
Participants who remained eligible for study participation were randomly allocated, using a 2:1 randomization ratio (abaloparatide:placebo) on Day 1, to receive treatment with either blinded abaloparatide 80 micrograms (mcg) per day or daily placebo subcutaneous (SC) injections.
Participants by arm
| Arm | Count |
|---|---|
| Abaloparatide Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen. | 149 |
| Placebo Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen. | 79 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 3 |
| Overall Study | Death (non-treatment emergent) | 1 | 0 |
| Overall Study | Lost to Follow-up | 7 | 1 |
| Overall Study | Other than Specified | 2 | 2 |
| Overall Study | Withdrawal by Subject | 17 | 9 |
Baseline characteristics
| Characteristic | Abaloparatide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 68.5 years STANDARD_DEVIATION 8.25 | 67.8 years STANDARD_DEVIATION 8.53 | 68.3 years STANDARD_DEVIATION 8.34 |
| Lumbar Spine Bone Mineral Density (BMD) T-score | -2.11 BMD T-Score STANDARD_DEVIATION 1.119 | -2.05 BMD T-Score STANDARD_DEVIATION 1.217 | -2.09 BMD T-Score STANDARD_DEVIATION 1.152 |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 23 Participants | 13 Participants | 36 Participants |
| Race/Ethnicity, Customized Ethnicity: MIssing | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 124 Participants | 66 Participants | 190 Participants |
| Race/Ethnicity, Customized Ethnicity: Unknown | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: Asian | 8 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Race: Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: White | 140 Participants | 76 Participants | 216 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 149 Participants | 79 Participants | 228 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 149 | 0 / 79 |
| other Total, other adverse events | 73 / 149 | 29 / 79 |
| serious Total, serious adverse events | 8 / 149 | 4 / 79 |
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. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health.
Time frame: Baseline, Month 12
Population: Intent-to-Treat (ITT) Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Lumbar Spine BMD at Month 12 | 8.4820 percent change | Standard Error 0.5353 |
| Placebo | Percent Change From Baseline in Lumbar Spine BMD at Month 12 | 1.1654 percent change | Standard Error 0.7235 |
p-value: <0.000199% CI: [5.0668, 9.5663]ANCOVA
Secondary
Number of Participants With New Clinical Fractures
Radiological evaluations were performed to identify any new clinical fractures (occurring after the screening visit).
Time frame: Baseline through Month 12
Population: ITT Population: All participants randomized into the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abaloparatide | Number of Participants With New Clinical Fractures | 1 Participants |
| Placebo | Number of Participants With New Clinical Fractures | 3 Participants |
Secondary
Percent Change From Baseline in Distal One-third Radius BMD at Month 12
Distal one-third radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health.
Time frame: Baseline, Month 12
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Distal One-third Radius BMD at Month 12 | -0.0138 percent change | Standard Error 0.3253 |
| Placebo | Percent Change From Baseline in Distal One-third Radius BMD at Month 12 | 0.7066 percent change | Standard Error 0.4285 |
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. Positive changes from baseline indicate improvement in bone health.
Time frame: Baseline, Month 12
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Femoral Neck BMD at Month 12 | 2.9766 percent change | Standard Error 0.3448 |
| Placebo | Percent Change From Baseline in Femoral Neck BMD at Month 12 | 0.1545 percent change | Standard Error 0.4527 |
p-value: <0.000199% CI: [1.3972, 4.2471]ANCOVA
Secondary
Percent Change From Baseline in Femoral Neck BMD at Month 6
Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.
Time frame: Baseline, Month 6
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Femoral Neck BMD at Month 6 | 1.4790 percent change | Standard Error 0.2714 |
| Placebo | Percent Change From Baseline in Femoral Neck BMD at Month 6 | -0.1884 percent change | Standard Error 0.3569 |
Secondary
Percent Change From Baseline in Femoral Neck Volumetric BMD as Measured by QCT at Month 12
QCT scans were evaluated by a central imaging laboratory.
Time frame: Baseline, Month 12
Population: Only 2 participants per reporting group had volumetric BMD measured by QCT at baseline and Month 12, therefore, no data is reported here to maintain participant confidentiality.
Secondary
Percent Change From Baseline in Lumbar Spine BMD at Month 6
Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health.
Time frame: Baseline, Month 6
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Lumbar Spine BMD at Month 6 | 5.5436 percent change | Standard Error 0.4127 |
| Placebo | Percent Change From Baseline in Lumbar Spine BMD at Month 6 | 0.6418 percent change | Standard Error 0.5472 |
Secondary
Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Month 12
Blood samples were taken to measure s-CTX. Elevated levels of s-CTX indicate increased bone resorption (bone loss).
Time frame: Baseline, Month 12
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed is the total number of participants who had s-CTX evaluation at Baseline and Month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Month 12 | 89.639 percent change | Standard Deviation 206.7227 |
| Placebo | Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Month 12 | 15.359 percent change | Standard Deviation 40.3351 |
Secondary
Percent Change From Baseline in Serum Procollagen Type I N-terminal Propeptide (s-PINP) at Month 12
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, Month 12
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed is the total number of participants who had s-PINP evaluation at Baseline and Month 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Serum Procollagen Type I N-terminal Propeptide (s-PINP) at Month 12 | 225.919 percent change | Standard Deviation 416.4173 |
| Placebo | Percent Change From Baseline in Serum Procollagen Type I N-terminal Propeptide (s-PINP) at Month 12 | 0.291 percent change | Standard Deviation 31.8038 |
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. Positive changes from baseline indicate improvement in bone health.
Time frame: Baseline, Month 12
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Total Hip BMD at Month 12 | 2.1351 percent change | Standard Error 0.2711 |
| Placebo | Percent Change From Baseline in Total Hip BMD at Month 12 | 0.0143 percent change | Standard Error 0.3543 |
p-value: <0.000199% CI: [0.9948, 3.2469]ANCOVA
Secondary
Percent Change From Baseline in Total Hip Volumetric BMD as Measured by Quantitative Computed Tomography (QCT) at Month 12
QCT scans were evaluated by a central imaging laboratory.
Time frame: Baseline, Month 12
Population: Only 2 participants per reporting group had volumetric BMD measured by QCT at baseline and Month 12, therefore, no data is reported here to maintain participant confidentiality.
Secondary
Percent Change From Baseline in Ultra-Distal Radius BMD at Month 12
Ultra-distal radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health.
Time frame: Baseline, Month 12
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change From Baseline in Ultra-Distal Radius BMD at Month 12 | 1.4358 percent change | Standard Error 0.4236 |
| Placebo | Percent Change From Baseline in Ultra-Distal Radius BMD at Month 12 | -0.1915 percent change | Standard Error 0.5722 |
Secondary
Percent Change in Total Hip BMD From Baseline at Month 6
Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health.
Time frame: Baseline, Month 6
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abaloparatide | Percent Change in Total Hip BMD From Baseline at Month 6 | 1.3888 percent change | Standard Error 0.2142 |
| Placebo | Percent Change in Total Hip BMD From Baseline at Month 6 | 0.0267 percent change | Standard Error 0.279 |
Secondary
Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip
Lumbar spine, femoral neck, and total hip BMD were assessed by DXA scans evaluated by a central imaging laboratory.
Time frame: Month 12
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abaloparatide | Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip | BMD Increase >0% at All Three Sites | 67.2 percentage of participants |
| Abaloparatide | Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip | BMD Increase >3% at All Three Sites | 31.9 percentage of participants |
| Abaloparatide | Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip | BMD Increase >6% at All Three Sites | 9.2 percentage of participants |
| Placebo | Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip | BMD Increase >0% at All Three Sites | 15.2 percentage of participants |
| Placebo | Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip | BMD Increase >3% at All Three Sites | 1.5 percentage of participants |
| Placebo | Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip | BMD Increase >6% at All Three Sites | 0.0 percentage of participants |
Secondary
Percent of Participants With Change in Disease Status
The percentage of participants converting from the categories of osteoporosis to osteopenia or from osteopenia to normal at End of Treatment (Month 12) was assessed. Osteoporosis was defined as lumbar spine or total hip BMD T-score ≤ -2.5. Osteopenia was defined as one of the following: * Lumbar spine \> -2.5 and total hip BMD T-score \> -2.5 and \< -1.0 * Lumbar spine \> -2.5 and \< -1.0 and total hip BMD T-score \> -2.5 * Normal was defined as lumbar spine and total hip BMD T-score ≥ -1.0.
Time frame: Baseline through Month 12
Population: ITT Population: All participants randomized into the study. Here, overall number of participants analyzed is the total number of participants who had baseline evaluation and also had end of treatment BMD disease category evaluation (normal, osteopenia, and osteoporosis).~.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abaloparatide | Percent of Participants With Change in Disease Status | Osteoporosis to Normal | 2.9 percentage of participants |
| Abaloparatide | Percent of Participants With Change in Disease Status | Osteopenia to Osteoporosis | 0 percentage of participants |
| Abaloparatide | Percent of Participants With Change in Disease Status | Osteoporosis to Osteopenia | 57.1 percentage of participants |
| Abaloparatide | Percent of Participants With Change in Disease Status | Normal to Osteopenia or Osteoporosis | 0 percentage of participants |
| Abaloparatide | Percent of Participants With Change in Disease Status | Osteopenia to Normal | 8.8 percentage of participants |
| Placebo | Percent of Participants With Change in Disease Status | Normal to Osteopenia or Osteoporosis | 0 percentage of participants |
| Placebo | Percent of Participants With Change in Disease Status | Osteoporosis to Normal | 0 percentage of participants |
| Placebo | Percent of Participants With Change in Disease Status | Osteopenia to Normal | 8.0 percentage of participants |
| Placebo | Percent of Participants With Change in Disease Status | Osteoporosis to Osteopenia | 12.8 percentage of participants |
| Placebo | Percent of Participants With Change in Disease Status | Osteopenia to Osteoporosis | 12.0 percentage of participants |