Postmenopausal Osteoporosis
Conditions
Brief summary
This 2 arm study will investigate the efficacy and safety of Bonviva (150mg po monthly) in the prevention of glucocorticoid-induced osteoporosis in post-menopausal women. Patients will be randomized to receive either Bonviva 150mg po or placebo monthly, with vitamin D and calcium supplementation. The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.
Interventions
DRUGPlacebo
po monthly for 12 months
DRUGibandronate
150mg po monthly for 12 months
Sponsors
GlaxoSmithKline
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* post-menopausal women, 50-85 years of age; * any inflammatory rheumatoid disease including polymyalgia rheumatica; * receiving treatment with 5-15 mg/day of prednisolone.
Exclusion criteria
* previous treatment with an iv bisphosphonate at any time; * previous treatment with an oral bisphosphonate within the last 6 months, \>1 month of treatment within last year, or \>3 months of treatment within last 2 years; * treatment with parathyroid hormone in last 2 years; * inability to stand or sit in an upright position for at least 60 minutes; * inability to swallow a tablet whole; * history of major gastrointestinal disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at Month 12 | Baseline and Month 12 | Lumbar spine BMD was measured at Baseline, and Months 6 and 12 using dual-energy x-ray absorptiometry (DXA). Percent change from Baseline to Month 12 was calculated using analysis of covariance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Mean Lumbar Spine BMD at Month 6 | Baseline and Month 6 | Lumbar spine BMD was measured at Baseline and Month 6 using DXA. Percent change from Baseline to Month 6 was calculated using analysis of covariance. |
| Percent Change From Baseline in Mean Total Hip BMD at Month 6 and Month 12 | Baseline and Months 6 and 12 | Left total hip BMD was measured by DXA at Baseline, and Months 6 and 12. If there was prosthesis of left hip, the measurement of right total hip BMD was done by DXA. Percent change from Baseline to Months 6 and 12 was calculated using analysis of (co)variance for repeated measurements. |
| Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | Baseline and Months 1, 6 and 12 | Serum C-terminal Telopeptide of Type 1 Collagen (sCTX), Serum Procollagen Type 1 N-terminal Propeptide (P1NP) and Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP) are measures of bone resorption and are measured as nanograms per milliliter (ng/mL). Percent change from Baseline to Months 1, 6 and 12 was calculated using analysis of covariance for repeated measurements. |
| Percentage of Participants Withdrawn Due to Worsening in BMD at 6 Months and/or Worsening in BMD at Least 7 Percent (%) at Any Site at 6 Months | Month 6 | Worsening in BMD was defined as BMD T-score at any site less than or equal to (≤) - 2.5 standard deviations and/or worsening in BMD of at least 7% at any site. |
Countries
Finland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibandronate Participants received 150 mg ibandronate tablet orally once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day. | 68 |
| Placebo Participants received oral placebo tablet once a month for 12 months. Participants also received 1000 mg calcium and 800 IU Vitamin D per day. | 72 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative reasons | 0 | 1 |
| Overall Study | Adverse Event | 7 | 3 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Violation of inclusion/exclusion | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Ibandronate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 7.9 | 63.2 years STANDARD_DEVIATION 6.83 | 63.79 years STANDARD_DEVIATION 7.39 |
| Sex: Female, Male Female | 68 Participants | 72 Participants | 140 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 | — / — | — / — |
| other Total, other adverse events | 19 / 70 | 26 / 70 |
| serious Total, serious adverse events | 10 / 70 | 6 / 70 |
Outcome results
Primary
Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at Month 12
Lumbar spine BMD was measured at Baseline, and Months 6 and 12 using dual-energy x-ray absorptiometry (DXA). Percent change from Baseline to Month 12 was calculated using analysis of covariance.
Time frame: Baseline and Month 12
Population: Intent-to-treat (ITT) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibandronate | Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at Month 12 | 3.2 percent change in BMD | Standard Deviation 3.7 |
| Placebo | Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at Month 12 | -0.1 percent change in BMD | Standard Deviation 3 |
p-value: <0.00195% CI: [2.09, 4.41]ANCOVA
Secondary
Percentage of Participants Withdrawn Due to Worsening in BMD at 6 Months and/or Worsening in BMD at Least 7 Percent (%) at Any Site at 6 Months
Worsening in BMD was defined as BMD T-score at any site less than or equal to (≤) - 2.5 standard deviations and/or worsening in BMD of at least 7% at any site.
Time frame: Month 6
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibandronate | Percentage of Participants Withdrawn Due to Worsening in BMD at 6 Months and/or Worsening in BMD at Least 7 Percent (%) at Any Site at 6 Months | 0.0 percentage of participants |
| Placebo | Percentage of Participants Withdrawn Due to Worsening in BMD at 6 Months and/or Worsening in BMD at Least 7 Percent (%) at Any Site at 6 Months | 0.0 percentage of participants |
Secondary
Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12
Serum C-terminal Telopeptide of Type 1 Collagen (sCTX), Serum Procollagen Type 1 N-terminal Propeptide (P1NP) and Serum Bone Tartrate-resistant Acid Phosphatase Isoform 5b (TRACP) are measures of bone resorption and are measured as nanograms per milliliter (ng/mL). Percent change from Baseline to Months 1, 6 and 12 was calculated using analysis of covariance for repeated measurements.
Time frame: Baseline and Months 1, 6 and 12
Population: ITT population; n=number of participants analyzed at the specified visit for the given parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | sCTX Month 6 (n=62,66) | -53.3 percent change in bone turnover markers | Standard Deviation 24.3 |
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | P1NP Month 12 (n=64,67) | -48.8 percent change in bone turnover markers | Standard Deviation 37.2 |
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | P1NP Month 1 (n=68,68) | -23.8 percent change in bone turnover markers | Standard Deviation 17.2 |
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | TRACP Month 1 (n=68,68) | -31.3 percent change in bone turnover markers | Standard Deviation 12 |
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | sCTX Month 12 (n=65,65) | -42.0 percent change in bone turnover markers | Standard Deviation 27.9 |
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | TRACP Month 6 (n=62,66) | -32.9 percent change in bone turnover markers | Standard Deviation 14.8 |
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | P1NP Month 6 (n=60,66) | -62.5 percent change in bone turnover markers | Standard Deviation 16.3 |
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | TRACP Month 12 (n=65,67) | -27.4 percent change in bone turnover markers | Standard Deviation 16.5 |
| Ibandronate | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | sCTX Month 1 (n=68,68) | -44.7 percent change in bone turnover markers | Standard Deviation 36.5 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | TRACP Month 12 (n=65,67) | -6.3 percent change in bone turnover markers | Standard Deviation 18 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | sCTX Month 1 (n=68,68) | -3.8 percent change in bone turnover markers | Standard Deviation 33.3 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | sCTX Month 6 (n=62,66) | -3.5 percent change in bone turnover markers | Standard Deviation 48 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | sCTX Month 12 (n=65,65) | 11.6 percent change in bone turnover markers | Standard Deviation 82.4 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | P1NP Month 1 (n=68,68) | -2.3 percent change in bone turnover markers | Standard Deviation 22.5 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | P1NP Month 6 (n=60,66) | -3.7 percent change in bone turnover markers | Standard Deviation 44.5 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | P1NP Month 12 (n=64,67) | 12.5 percent change in bone turnover markers | Standard Deviation 54.6 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | TRACP Month 1 (n=68,68) | -7.3 percent change in bone turnover markers | Standard Deviation 11.9 |
| Placebo | Percent Change From Baseline in Bone Turnover Markers at Month 1, Month 6 and Month 12 | TRACP Month 6 (n=62,66) | -7.1 percent change in bone turnover markers | Standard Deviation 17 |
Comparison: P1NP at Month 12p-value: <0.001ANCOVA
Comparison: TRACP at Month 1p-value: <0.001ANCOVA
Comparison: P1NP at Month 6p-value: <0.001ANCOVA
Comparison: sCTX at Month 1p-value: <0.001ANCOVA
Comparison: sCTX at Month 6p-value: <0.001ANCOVA
Comparison: sCTX at Month 12p-value: <0.001ANCOVA
Comparison: P1NP at Month 1p-value: <0.001ANCOVA
Comparison: TRACP at Month 6p-value: <0.001ANCOVA
Comparison: TRACP at Month 12p-value: <0.001ANCOVA
Secondary
Percent Change From Baseline in Mean Lumbar Spine BMD at Month 6
Lumbar spine BMD was measured at Baseline and Month 6 using DXA. Percent change from Baseline to Month 6 was calculated using analysis of covariance.
Time frame: Baseline and Month 6
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibandronate | Percent Change From Baseline in Mean Lumbar Spine BMD at Month 6 | 2.6 percent change in BMD | Standard Deviation 3.1 |
| Placebo | Percent Change From Baseline in Mean Lumbar Spine BMD at Month 6 | 0.3 percent change in BMD | Standard Deviation 2.8 |
p-value: <0.00195% CI: [1.22, 3.23]ANCOVA
Secondary
Percent Change From Baseline in Mean Total Hip BMD at Month 6 and Month 12
Left total hip BMD was measured by DXA at Baseline, and Months 6 and 12. If there was prosthesis of left hip, the measurement of right total hip BMD was done by DXA. Percent change from Baseline to Months 6 and 12 was calculated using analysis of (co)variance for repeated measurements.
Time frame: Baseline and Months 6 and 12
Population: ITT population; number (n) equals (=) number of participants analyzed at the specified visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibandronate | Percent Change From Baseline in Mean Total Hip BMD at Month 6 and Month 12 | Month 6 (n=62,66) | 0.7 percent change in BMD | Standard Deviation 1.9 |
| Ibandronate | Percent Change From Baseline in Mean Total Hip BMD at Month 6 and Month 12 | Month 12 (n=66,65) | 1.2 percent change in BMD | Standard Deviation 2.2 |
| Placebo | Percent Change From Baseline in Mean Total Hip BMD at Month 6 and Month 12 | Month 6 (n=62,66) | 0.0 percent change in BMD | Standard Deviation 2.1 |
| Placebo | Percent Change From Baseline in Mean Total Hip BMD at Month 6 and Month 12 | Month 12 (n=66,65) | -0.7 percent change in BMD | Standard Deviation 2.5 |
Comparison: Month 6p-value: 0.12295% CI: [-0.15, 1.25]ANCOVA
Comparison: Month 12p-value: <0.00195% CI: [0.96, 2.66]ANCOVA