Postmenopausal Osteoporosis
Conditions
Keywords
Osteoporosis, Bone Diseases, Metabolic, Bone Diseases, Bone Density Conservation Agents
Brief summary
This study is designed to provide information about the bone anabolic properties and absorption profile of Unigene's PTH Analog when administered as oral tablets over a period of 24 weeks to postmenopausal women with osteoporosis.
Detailed description
The choice of a 24-week treatment period was based on published studies of PTH which demonstrate its potential to produce a statistically significant increase in BMD in patients with postmenopausal osteoporosis within that observation period.
Interventions
DRUGPTH analog
A recombinant 1-31 amino acid fragment of PTH.
DRUGPlacebo
DRUGForsteo (Teriparatide)
A recombinant 1-34 amino acid fragment of PTH.
Sponsors
GlaxoSmithKline
Unigene Laboratories Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Healthy postmenopausal women (45-80 years old) with a diagnosis of osteoporosis
Exclusion criteria
* Use of estrogen or hormone replacement therapy * Use of bisphosphonates, strontium ranelate or denosumab * Use of parathyroid analogues or other bone metabolic agents * Medical conditions which might alter bone metabolism * Any known clinically significant disease affecting calcium metabolism or history of metabolic disorders including Paget's disease, osteogenesis imperfecta, or osteomalacia * Impairment of thyroid function
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| % Change From Baseline BMD in L1-L4 Axial Lumbar Spine at Week 24 | 24 weeks from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % Change From Baseline in Bone Resorption Marker (CTx-1) at Week 24 | 24 weeks from baseline | Serum collagen type I (CTx-1) fragments generated during osteoclastic bone turnover are biomarkers for bone resorption. β-CrossLaps electrochemiluminescent sandwich immunoassay was used. |
| Systemic Absorption of PTH at Week 24 | 24 weeks | AUC: (PTH analog tablets timepoints - baseline to 5.75 hours) (Forsteo injection timepoints - baseline to 2 hours) |
| % Change From Baseline in Bone Formation Marker (P1NP) at Week 24 | 24 weeks from baseline | — |
Countries
Denmark, Estonia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Forsteo (Teriparatide) Teriparatide : 20 mcg SC Injection, once daily | 32 |
| PTH Analog Tablets PTH analog : 5 mg tablets, once daily | 33 |
| Placebo Placebo : matching tablets, once daily | 32 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Forsteo (Teriparatide) | PTH Analog Tablets | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 66.5 years STANDARD_DEVIATION 6.99 | 67.4 years STANDARD_DEVIATION 3.95 | 66.1 years STANDARD_DEVIATION 6.09 | 66.7 years STANDARD_DEVIATION 5.77 |
| Sex: Female, Male Female | 32 Participants | 33 Participants | 32 Participants | 97 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 32 | 30 / 33 | 21 / 32 |
| serious Total, serious adverse events | 1 / 32 | 2 / 33 | 2 / 32 |
Outcome results
Primary
% Change From Baseline BMD in L1-L4 Axial Lumbar Spine at Week 24
Time frame: 24 weeks from baseline
Population: mITT Population: all subjects who received at least one dose of treatment and at least one post-baseline BMD value. Missing data imputation for patients who completed Week 12 but not the full 24-week period, data was imputed using the LOCF. No data imputation was performed for Week 24, if the Week 12 data was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Forsteo (Teriparatide) | % Change From Baseline BMD in L1-L4 Axial Lumbar Spine at Week 24 | 5.07 percentage of change | Standard Deviation 3.543 |
| PTH Analog Tablets | % Change From Baseline BMD in L1-L4 Axial Lumbar Spine at Week 24 | 2.21 percentage of change | Standard Deviation 2.503 |
| Placebo | % Change From Baseline BMD in L1-L4 Axial Lumbar Spine at Week 24 | -0.17 percentage of change | Standard Deviation 2.739 |
Secondary
% Change From Baseline in Bone Formation Marker (P1NP) at Week 24
Time frame: 24 weeks from baseline
Population: mITT Population: all subjects who received at least one dose of treatment and at least one post-baseline BMD value. Missing data imputation for patients who completed Week 12 but not the full 24-week period, data was imputed using the LOCF. No data imputation was performed for Week 24, if the Week 12 data was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Forsteo (Teriparatide) | % Change From Baseline in Bone Formation Marker (P1NP) at Week 24 | 210.07 percentage of change | Standard Deviation 202.613 |
| PTH Analog Tablets | % Change From Baseline in Bone Formation Marker (P1NP) at Week 24 | 12.05 percentage of change | Standard Deviation 37.055 |
| Placebo | % Change From Baseline in Bone Formation Marker (P1NP) at Week 24 | -1.75 percentage of change | Standard Deviation 27.459 |
Secondary
% Change From Baseline in Bone Resorption Marker (CTx-1) at Week 24
Serum collagen type I (CTx-1) fragments generated during osteoclastic bone turnover are biomarkers for bone resorption. β-CrossLaps electrochemiluminescent sandwich immunoassay was used.
Time frame: 24 weeks from baseline
Population: mITT Population: all subjects who received at least one dose of treatment and at least one post-baseline BMD value. Missing data imputation for patients who completed Week 12 but not the full 24-week period, data was imputed using the LOCF. No data imputation was performed for Week 24, if the Week 12 data was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Forsteo (Teriparatide) | % Change From Baseline in Bone Resorption Marker (CTx-1) at Week 24 | 113.32 percentage of change | Standard Deviation 102.932 |
| PTH Analog Tablets | % Change From Baseline in Bone Resorption Marker (CTx-1) at Week 24 | 12.72 percentage of change | Standard Deviation 36.547 |
| Placebo | % Change From Baseline in Bone Resorption Marker (CTx-1) at Week 24 | 15.13 percentage of change | Standard Deviation 23.94 |
Secondary
Systemic Absorption of PTH at Week 24
AUC: (PTH analog tablets timepoints - baseline to 5.75 hours) (Forsteo injection timepoints - baseline to 2 hours)
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Forsteo (Teriparatide) | Systemic Absorption of PTH at Week 24 | 152 pg* hr/mL | Standard Deviation 65.7 |
| PTH Analog Tablets | Systemic Absorption of PTH at Week 24 | 165 pg* hr/mL | Standard Deviation 180 |
Post Hoc
Number of Participants With AEs as a Measure of Safety and Tolerability
Time frame: 24 weeks
Population: Overall Summary of Adverse Events - Each subject with an event is counted only once although they may have several events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Forsteo (Teriparatide) | Number of Participants With AEs as a Measure of Safety and Tolerability | 23 participants |
| PTH Analog Tablets | Number of Participants With AEs as a Measure of Safety and Tolerability | 30 participants |
| Placebo | Number of Participants With AEs as a Measure of Safety and Tolerability | 21 participants |