Osteoporosis
Conditions
Brief summary
The purpose of this study is to compare the effect of injectable teriparatide to intranasal salmon calcitonin on lumbar spine bone mineral density, in the treatment of Chinese patients with established osteoporosis
Interventions
DRUGTeriparatide
Subcutaneous, 20 micrograms/day, 24 weeks
Intranasal, 200 International Units (IU)/day, 24 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of osteoporosis * No other severe disabling conditions * Should have at least 1 vertebral or non-vertebral prevalent fracture, and bone mineral density T-score should be less than -2.5 * Ambulatory * Men (aged 40 to 85 years) or postmenopausal women (aged 55 to 85 years)
Exclusion criteria
* History of a disease that affects bone metabolism * History of treatment with any drug that may significantly affect bone metabolism * History or presence of liver disease * History or presence of kidney disease * History of excessive alcohol drinking or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline to 24 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD), Postmenopausal Women | Baseline to 24 weeks | Lumbar spine bone mineral density (milligrams per square centimeter) was measured by dual energy X-ray absorptiometry (DXA). Change = Endpoint minus baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline to 24 Week Endpoint in Total Hip Bone Mineral Density (BMD), Postmenopausal Women | Baseline to 24 weeks | Total hip bone mineral density (milligrams per square centimeter) was measured by dual energy X-ray absorptiometry (DXA). Change = Endpoint minus baseline. |
| Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Postmenopausal Women | Baseline to 12 weeks and 24 weeks | Measures of serum osteocalcin (nanograms per milliliter). Change = Endpoint minus baseline. |
| Percentage Change From Baseline to 24 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD), Men | Baseline to 24 weeks | Lumbar spine bone mineral density (milligrams per square centimeter) was measured by dual energy X-ray absorptiometry (DXA). Change = Endpoint minus baseline. |
| Percentage Change From Baseline to 24 Week Endpoint in Total Hip Bone Mineral Density (BMD), Men | Baseline to 24 weeks | Total hip bone mineral density (milligrams per square centimeter) was measured by dual energy X-ray absorptiometry (DXA). Change = Endpoint minus baseline. |
| Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Men | Baseline to 12 weeks and 24 weeks | Measures of serum osteocalcin (nanograms per milliliter). Change = Endpoint minus baseline. |
Countries
China
Participant flow
Pre-assignment details
364 participants were randomized, but 2 females did not receive study drug and are not included in any of the analyses.
Participants by arm
| Arm | Count |
|---|---|
| Teriparatide - Females Subcutaneous, 20 micrograms/day, 24 weeks | 218 |
| Calcitonin - Females Intranasal, 200 International Units (IU)/day, 24 weeks | 109 |
| Teriparatide - Males Subcutaneous, 20 micrograms/day, 24 weeks | 24 |
| Calcitonin - Males Intranasal, 200 IU/day, 24 weeks | 11 |
| Total | 362 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 0 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 0 |
| Overall Study | Protocol Violation | 3 | 4 | 0 | 0 |
| Overall Study | Sponsor Decision | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 14 | 4 | 1 | 0 |
Baseline characteristics
| Characteristic | Teriparatide - Females | Calcitonin - Females | Teriparatide - Males | Calcitonin - Males | Total |
|---|---|---|---|---|---|
| Age Continuous | 69.09 years STANDARD_DEVIATION 6.95 | 67.81 years STANDARD_DEVIATION 7.22 | 68.27 years STANDARD_DEVIATION 8.28 | 67.39 years STANDARD_DEVIATION 11.01 | 68.60 years STANDARD_DEVIATION 7.26 |
| Duration of Osteoporosis | 3.6 years STANDARD_DEVIATION 5.33 | 3.1 years STANDARD_DEVIATION 4.16 | 1.9 years STANDARD_DEVIATION 2.24 | 2.4 years STANDARD_DEVIATION 2.54 | 3.30 years STANDARD_DEVIATION 4.8 |
| Race/Ethnicity East Asian | 218 participants | 109 participants | 24 participants | 11 participants | 362 participants |
| Region of Enrollment China | 218 participants | 109 participants | 24 participants | 11 participants | 362 participants |
| Sex: Female, Male Female | 218 Participants | 109 Participants | 0 Participants | 0 Participants | 327 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 24 Participants | 11 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 67 / — | 26 / — | 7 / — | 0 / — |
| serious Total, serious adverse events | 8 / — | 1 / — | 2 / — | 0 / — |
Outcome results
Primary
Percentage Change From Baseline to 24 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD), Postmenopausal Women
Lumbar spine bone mineral density (milligrams per square centimeter) was measured by dual energy X-ray absorptiometry (DXA). Change = Endpoint minus baseline.
Time frame: Baseline to 24 weeks
Population: Number of Intention to Treat patients with baseline and at least one post baseline measurement. Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide - Females | Percentage Change From Baseline to 24 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD), Postmenopausal Women | 6.04 percentage change in lumbar spine BMD | Standard Error 0.48 |
| Calcitonin - Females | Percentage Change From Baseline to 24 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD), Postmenopausal Women | 1.65 percentage change in lumbar spine BMD | Standard Error 0.65 |
Comparison: Null hypothesis=no difference between percentage changes from baseline in lumbar spine bone mineral density for female patients receiving teriparatide compared to female patients receiving calcitonin.p-value: <0.000195% CI: [2.89, 5.89]ANCOVA
Secondary
Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Men
Measures of serum osteocalcin (nanograms per milliliter). Change = Endpoint minus baseline.
Time frame: Baseline to 12 weeks and 24 weeks
Population: Number of Intention to Treat patients with measurements at respective visit.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide - Females | Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Men | Week 12 Percentage Change (n=21, n=11) | 107.27 percentage change in osteocalcin | Inter-Quartile Range 14.88 |
| Teriparatide - Females | Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Men | Week 24 Percentage Change (n=21, n=11) | 79.26 percentage change in osteocalcin | Inter-Quartile Range 26.94 |
| Calcitonin - Females | Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Men | Week 12 Percentage Change (n=21, n=11) | 4.35 percentage change in osteocalcin | Inter-Quartile Range 13.48 |
| Calcitonin - Females | Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Men | Week 24 Percentage Change (n=21, n=11) | -17.65 percentage change in osteocalcin | Inter-Quartile Range 5.21 |
p-value: 0.0026Wilcoxon Rank-Sum Test
p-value: 0.0006Wilcoxon Rank-Sum Test
Secondary
Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Postmenopausal Women
Measures of serum osteocalcin (nanograms per milliliter). Change = Endpoint minus baseline.
Time frame: Baseline to 12 weeks and 24 weeks
Population: Number of Intention to Treat patients with measurements at respective visits.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide - Females | Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Postmenopausal Women | Week 12 Percentage Change (n=202, n=102) | 113.87 percentage change in osteocalcin | Inter-Quartile Range 21.46 |
| Teriparatide - Females | Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Postmenopausal Women | Week 24 Percentage Change (n=191, n=97) | 137.45 percentage change in osteocalcin | Inter-Quartile Range 36.53 |
| Calcitonin - Females | Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Postmenopausal Women | Week 24 Percentage Change (n=191, n=97) | -10.58 percentage change in osteocalcin | Inter-Quartile Range 8.21 |
| Calcitonin - Females | Percentage Change From Baseline to 12 Weeks and 24 Weeks in Osteocalcin, Postmenopausal Women | Week 12 Percentage Change (n=202, n=102) | -7.67 percentage change in osteocalcin | Inter-Quartile Range 5.43 |
p-value: <0.0001Wilcoxon Rank-Sum Test
p-value: <0.0001Wilcoxon Rank-Sum Test
Secondary
Percentage Change From Baseline to 24 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD), Men
Lumbar spine bone mineral density (milligrams per square centimeter) was measured by dual energy X-ray absorptiometry (DXA). Change = Endpoint minus baseline.
Time frame: Baseline to 24 weeks
Population: Number of Intention to Treat patients with baseline plus at least one post baseline measurement. Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide - Females | Percentage Change From Baseline to 24 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD), Men | 6.01 percentage change in lumbar spine BMD | Standard Error 1.2 |
| Calcitonin - Females | Percentage Change From Baseline to 24 Week Endpoint in Lumbar Spine Bone Mineral Density (BMD), Men | 3.38 percentage change in lumbar spine BMD | Standard Error 1.77 |
p-value: 0.240995% CI: [-1.87, 7.13]ANCOVA
Secondary
Percentage Change From Baseline to 24 Week Endpoint in Total Hip Bone Mineral Density (BMD), Men
Total hip bone mineral density (milligrams per square centimeter) was measured by dual energy X-ray absorptiometry (DXA). Change = Endpoint minus baseline.
Time frame: Baseline to 24 weeks
Population: Number of Intention to Treat patients with baseline plus at least one post baseline measurement. Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide - Females | Percentage Change From Baseline to 24 Week Endpoint in Total Hip Bone Mineral Density (BMD), Men | 0.37 percentage change in total hip BMD | Standard Error 1.11 |
| Calcitonin - Females | Percentage Change From Baseline to 24 Week Endpoint in Total Hip Bone Mineral Density (BMD), Men | 1.34 percentage change in total hip BMD | Standard Error 1.54 |
p-value: 0.615695% CI: [-4.85, 2.92]ANCOVA
Secondary
Percentage Change From Baseline to 24 Week Endpoint in Total Hip Bone Mineral Density (BMD), Postmenopausal Women
Total hip bone mineral density (milligrams per square centimeter) was measured by dual energy X-ray absorptiometry (DXA). Change = Endpoint minus baseline.
Time frame: Baseline to 24 weeks
Population: Number of Intention to Treat patients with baseline plus at least one post baseline measurement. Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide - Females | Percentage Change From Baseline to 24 Week Endpoint in Total Hip Bone Mineral Density (BMD), Postmenopausal Women | -0.53 percentage change in total hip BMD | Standard Error 0.44 |
| Calcitonin - Females | Percentage Change From Baseline to 24 Week Endpoint in Total Hip Bone Mineral Density (BMD), Postmenopausal Women | -0.62 percentage change in total hip BMD | Standard Error 0.59 |
p-value: 0.906295% CI: [-1.3, 1.46]ANCOVA