Osteopenia
Conditions
Brief summary
The primary purpose of the protocol is to evaluate the sensitivity of 3D-pQCT (3D-Peripheral Quantitative Computed Tomography) technology to detect minute changes in bone microarchitecture.
Detailed description
The 3D-pQCT equipment allows the evaluation of changes occurring within the bone at microarchitecture level, without the need for invasive bone biopsies. The primary objective is to evaluate the sensitivity of the technology to detect a difference between those treated with risedronate 35mg OAW (once a week) or placebo. Early phase postmenopausal women with osteopenia have been chosen because they have a more rapid and higher level of bone loss during the first few years of the menopause.
Interventions
DRUGPlacebo comparator
oral weekly for one year
DRUGrisedronate
35 mg risedronate, once a week for one year
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* cessation of menstruation (surgical or natural) between 6 and 36 months prior to study enrollment; * osteopenic * must have at least 1 evaluable radius and tibia, without history of fracture (traumatic or atraumatic) * BMI (body mass index) between 18 and 28 kg/m2 inclusive;
Exclusion criteria
* history of any generalized bone disease, including hyperparathyroidism, Paget's disease of bone, renal osteodystrophy, or any other acquired or congenital bone disease; or any known condition that would interfere with the assessment of DXA (dual-energy X-ray absorptiometry) at either the lumbar spine (3 non-evaluable lumbar vertebrae at lumbar spine L1 - L4) or the femoral neck. * clinical or radiological evidence of osteoporosis, such as atraumatic vertebral compression fracture (\* 20% reduction in anterior-to-posterior or middle-to-posterior height ratio; or 20% reduction of the anterior, middle, and/or posterior height as compared with the adjacent vertebrae) documented by spinal X ray or a history of osteoporosis-related atraumatic fracture of the hip or of the wrist; * glucocorticoid-induced osteopenia; * previous bisphosphonate therapy;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Trabecular Bone Volume to Tissue Volume at Distal Radius, Percent Change From Baseline to Month 12 | Baseline and Month 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compact Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Trabecular Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Average Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Compact Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Trabecular Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Lumbar Spine BMD, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Average Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Femoral Neck BMD, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Greater Trochanter BMD, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Type I Collagen C-Telopeptides, Serum, Percent Change From Baseline to Month 12 | Baseline and Month 12 | ELISA / enzyme-linked immunosorbent assay method by central lab |
| Procollagen Type 1 N-Propeptide, Percent Change From Baseline to Month 12 | Baseline and Month 12 | Electrochemiluminescence assay method by central lab |
| Height, Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
| Total Proximal Femur BMD (Bone Mineral Density), Percent Change From Baseline to Month 12 | Baseline and Month 12 | — |
Countries
Argentina, Australia, Canada, France, Germany, Switzerland, United Kingdom
Participant flow
Recruitment details
Screening started 3 April 2006
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo, 1 tablet weekly on the same day | 49 |
| Risedronate 35 mg risedronate tablet, orally, once weekly on the same day | 112 |
| Total | 161 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Did not take any study medication | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | Risedronate | Placebo | Total |
|---|---|---|---|
| Age Continuous | 52.6 years STANDARD_DEVIATION 1.8 | 52.5 years STANDARD_DEVIATION 2.2 | 52.6 years STANDARD_DEVIATION 2 |
| Race/Ethnicity, Customized Asian (Oriental) | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 107 Participants | 48 Participants | 155 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Multi-Racial | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Argentina | 15 participants | 6 participants | 21 participants |
| Region of Enrollment Australia | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Canada | 6 participants | 2 participants | 8 participants |
| Region of Enrollment France | 24 participants | 9 participants | 33 participants |
| Region of Enrollment Germany | 46 participants | 23 participants | 69 participants |
| Region of Enrollment Switzerland | 7 participants | 3 participants | 10 participants |
| Region of Enrollment United Kingdom | 12 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 112 Participants | 49 Participants | 161 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 | 38 / 49 | 76 / 110 |
| serious Total, serious adverse events | 5 / 49 | 7 / 110 |
Outcome results
Primary
Trabecular Bone Volume to Tissue Volume at Distal Radius, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: Primary Efficacy Population - all patients in ITT population who had no major protocol violations and had an evaluable distal radius BV/TV (trabecular bone volume to tissue volume) at baseline and Month 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Trabecular Bone Volume to Tissue Volume at Distal Radius, Percent Change From Baseline to Month 12 | -1.486 Percent Change |
| Risedronate | Trabecular Bone Volume to Tissue Volume at Distal Radius, Percent Change From Baseline to Month 12 | -1.255 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.709695% CI: [-0.995, 1.458]ANOVA
Secondary
Average Bone Density at Distal Radius, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: Per Protocol (PP) Population - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Average Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | -2.121 Percent Change |
| Risedronate | Average Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | -1.578 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.297395% CI: [-0.485, 1.571]ANOVA
Secondary
Average Bone Density at Distal Tibia, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Average Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | -0.440 Percent Change |
| Risedronate | Average Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | -0.106 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.456595% CI: [-0.551, 1.219]ANOVA
Secondary
Compact Bone Density at Distal Radius, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Compact Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | -0.786 Percent Change |
| Risedronate | Compact Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | -0.301 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.127595% CI: [-0.141, 1.11]ANOVA
Secondary
Compact Bone Density at Distal Tibia, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Compact Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | -0.784 Percent Change |
| Risedronate | Compact Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | -0.173 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.061495% CI: [-0.03, 1.252]ANOVA
Secondary
Femoral Neck BMD, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Femoral Neck BMD, Percent Change From Baseline to Month 12 | -1.422 Percent Change |
| Risedronate | Femoral Neck BMD, Percent Change From Baseline to Month 12 | -0.014 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.003695% CI: [0.469, 2.348]ANOVA
Secondary
Greater Trochanter BMD, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Greater Trochanter BMD, Percent Change From Baseline to Month 12 | -0.462 Percent Change |
| Risedronate | Greater Trochanter BMD, Percent Change From Baseline to Month 12 | 0.996 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.008795% CI: [0.375, 2.541]ANOVA
Secondary
Height, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Height, Percent Change From Baseline to Month 12 | -0.163 Percent Change |
| Risedronate | Height, Percent Change From Baseline to Month 12 | -0.071 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.138595% CI: [-0.03, 0.213]ANOVA
Secondary
Lumbar Spine BMD, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Lumbar Spine BMD, Percent Change From Baseline to Month 12 | -1.797 Percent Change |
| Risedronate | Lumbar Spine BMD, Percent Change From Baseline to Month 12 | 1.473 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: <0.000195% CI: [2.231, 4.31]ANOVA
Secondary
Procollagen Type 1 N-Propeptide, Percent Change From Baseline to Month 12
Electrochemiluminescence assay method by central lab
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Procollagen Type 1 N-Propeptide, Percent Change From Baseline to Month 12 | -5.762 Percent Change |
| Risedronate | Procollagen Type 1 N-Propeptide, Percent Change From Baseline to Month 12 | -46.031 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: <0.000195% CI: [-51.3, -29.238]ANOVA
Secondary
Total Proximal Femur BMD (Bone Mineral Density), Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Total Proximal Femur BMD (Bone Mineral Density), Percent Change From Baseline to Month 12 | -0.976 Percent Change |
| Risedronate | Total Proximal Femur BMD (Bone Mineral Density), Percent Change From Baseline to Month 12 | 0.468 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: <0.000195% CI: [0.748, 2.14]ANOVA
Secondary
Trabecular Bone Density at Distal Radius, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Trabecular Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | -1.820 Percent Change |
| Risedronate | Trabecular Bone Density at Distal Radius, Percent Change From Baseline to Month 12 | -1.156 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.33695% CI: [-0.697, 2.025]ANOVA
Secondary
Trabecular Bone Density at Distal Tibia, Percent Change From Baseline to Month 12
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Trabecular Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | 0.785 Percent Change |
| Risedronate | Trabecular Bone Density at Distal Tibia, Percent Change From Baseline to Month 12 | 0.725 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.921295% CI: [-1.258, 1.138]ANOVA
Secondary
Type I Collagen C-Telopeptides, Serum, Percent Change From Baseline to Month 12
ELISA / enzyme-linked immunosorbent assay method by central lab
Time frame: Baseline and Month 12
Population: PP - all patients in ITT population who had no major protocol violations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Type I Collagen C-Telopeptides, Serum, Percent Change From Baseline to Month 12 | 1.537 Percent Change |
| Risedronate | Type I Collagen C-Telopeptides, Serum, Percent Change From Baseline to Month 12 | -38.002 Percent Change |
Comparison: In Laib 1998, the mean and SD of the annual loss in distal radius BV/TV were reported to be 3.5% and 6.4%, respectively. Assuming the treatment difference and SD of the percent change in distal radius BV/TV for this study were the same, it required enrolling 52 patients for placebo and 104 for risedronate to ensure 80% power to achieve 0.05 level of significance. Sample size estimation based on 2-sided 2-sample t-test and assumed effective size of 0.54 and dropout rate of 20%.p-value: 0.000295% CI: [-59.957, -19.123]ANOVA