Post-Menopausal Osteoporosis
Conditions
Brief summary
This 2-arm study was designed to assess the long-term safety and tolerability of intravenous (IV) treatment with 2 mg or 3 mg Bonviva in women with post-menopausal osteoporosis who had previously completed Bonviva study BM16550 (DIVA study; NCT00048074). Patients received Bonviva either 2 mg IV every 2 months, or 3 mg IV every 3 months. Patients also received daily supplementation with vitamin D and calcium. The anticipated time on study treatment was 2+ years, and the target sample size was 500+ individuals.
Interventions
3 mg IV every 3 months for 3 years. All patients received a minimum of calcium 500 milligrams/day (upper limit 1500 mg/day) and Vitamin D 400 Internation Units/day (IU/day).
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Successful completion of Bonviva study BM16550 (NCT00048074), with at least 75% compliance * Ambulatory
Exclusion criteria
* Patients who completed the Bonviva study BM16550 (NCT00048074) \>3 months before the planned start date for this study * Malignant disease diagnosed since inclusion into previous study * Treatment with drugs affecting bone metabolism since inclusion into previous study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Baseline,12, 24 and 36 months | Relative change percent(%) from baseline of MA17904 and BM16550 (NCT00048074) in mean lumbar spine (L2-L4) BMD at 12, 24 and 36 months (i.e., 3, 4 and 5 years after initiation of BM16550)- Study MA17940.Percent change=\[(measure at time t - measure at baseline)/measure at baseline\]\*100%, where t=12, 24 and 36 months. The baseline value is used as a reference to calculate the relative change from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Baseline,12, 24 and 36 months | Relative change percent (%) from baseline of MA17904 and BM16550 (NCT00048074) in mean total hip BMD at 12, 24 and 36 months (i.e., 3, 4 and 5 years after initiation of BM16550)- Study MA17904. Percent change=\[(measure at time t - measure at baseline)/measure at baseline\]\*100%, where t=12, 24 and 36 months. The baseline value is used as a reference to calculate the relative change from baseline. |
| Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Baseline, 6, 12, 24 and 36 months (i.e., 2.5, 3, 4 and 5 years after initiation of BM16550) | Relative percent (%) change from baseline of MA17904 and BM16550 (NCT00048074) in serum C-telopeptide crosslinks of type I collagen (CTX) at trough at 6, 12, 24 and 36 months- Study MA17904. Percent change=\[(measure at time t - measure at baseline)/measure at baseline\]\*100%, where t=6, 12, 24 and 36 months. The baseline value is used as a reference to calculate the relative change from baseline. |
| Relative Percent Change From Baseline in Post-dose Suppression of Serum CTX at 6 Months | Baseline, 6 months | Relative percent (%) change from MA17904 baseline of post-dose suppression of serum C-telopeptide crosslinks of type I collagen (CTX) at 6 months- Study MA17904. Percent change=\[(measure at time t - measure at baseline)/measure at baseline\]\*100%, where t= 6 months. The baseline value is used as a reference to calculate the relative change from baseline. |
Countries
Australia, Belgium, Czechia, Denmark, France, Germany, Hungary, Italy, Mexico, Norway, Poland, South Africa, Spain, United Kingdom, United States
Participant flow
Recruitment details
Study enrollment was to occur at centers that had participated in BM16550 (NCT00048074) in North America, Mexico, Europe, Australia, and South Africa.
Pre-assignment details
Postmenopausal osteoporosis. Patients having completed study BM16550 (NCT00048074) and who had complied with the intravenous (IV) regimen during the second year of study BM16550 (NCT00048074) for 75% or more.
Participants by arm
| Arm | Count |
|---|---|
| 2 mg Ibandronate q2mo 2 mg ibandronate intravenously (IV) every 2 months (q2mo) for 3 years | 381 |
| 3 mg Ibandronate q3mo 3 mg ibandronate intravenously (IV) every 3 months (q3mo) for 3 years | 400 |
| Total | 781 |
Baseline characteristics
| Characteristic | 2 mg Ibandronate q2mo | 3 mg Ibandronate q3mo | Total |
|---|---|---|---|
| Age Continuous | 68.2 years STANDARD_DEVIATION 6.1 | 67.9 years STANDARD_DEVIATION 6 | 68.0 years STANDARD_DEVIATION 6 |
| BMI | 25.63 kg/m*2 STANDARD_DEVIATION 4.295 | 25.89 kg/m*2 STANDARD_DEVIATION 4.394 | 25.76 kg/m*2 STANDARD_DEVIATION 4.346 |
| Race/Ethnicity, Customized Black | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Caucasian/White | 363 participants | 388 participants | 751 participants |
| Race/Ethnicity, Customized Hispanic | 17 participants | 11 participants | 28 participants |
| Race/Ethnicity, Customized Oriental | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 381 Participants | 400 Participants | 781 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 | 265 / 381 | 285 / 400 |
| serious Total, serious adverse events | 90 / 381 | 84 / 400 |
Outcome results
Primary
Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months
Relative change percent(%) from baseline of MA17904 and BM16550 (NCT00048074) in mean lumbar spine (L2-L4) BMD at 12, 24 and 36 months (i.e., 3, 4 and 5 years after initiation of BM16550)- Study MA17940.Percent change=\[(measure at time t - measure at baseline)/measure at baseline\]\*100%, where t=12, 24 and 36 months. The baseline value is used as a reference to calculate the relative change from baseline.
Time frame: Baseline,12, 24 and 36 months
Population: ITT population: 3 mg group = 394, 2 mg group = 362. Analysis populations (AP) for Month 12: 3 mg group = 383, 2 mg group = 348; Month 24: 3 mg group = 374, 2 mg group = 332; Month 36: 3 mg group = 349, 2 mg group = 314.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Baseline | 0.7969 Percent change | Standard Deviation 0.0764 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Percent Change from Baseline at Month 12 | 0.8378 Percent change | Standard Deviation 3.192 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Percent Change from Baseline at Month 24 | 1.6785 Percent change | Standard Deviation 3.6494 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Percent Change from Baseline at Month 36 | 1.9813 Percent change | Standard Deviation 4.6619 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Percent Change from Baseline at Month 36 | 2.0559 Percent change | Standard Deviation 4.4747 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Baseline | 0.7861 Percent change | Standard Deviation 0.0824 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Percent Change from Baseline at Month 24 | 1.5742 Percent change | Standard Deviation 4.0665 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Mean Lumbar Spine Bone Mineral Density (BMD) at 12, 24 and 36 Months | Percent Change from Baseline at Month 12 | 0.8845 Percent change | Standard Deviation 3.6386 |
Secondary
Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months
Relative change percent (%) from baseline of MA17904 and BM16550 (NCT00048074) in mean total hip BMD at 12, 24 and 36 months (i.e., 3, 4 and 5 years after initiation of BM16550)- Study MA17904. Percent change=\[(measure at time t - measure at baseline)/measure at baseline\]\*100%, where t=12, 24 and 36 months. The baseline value is used as a reference to calculate the relative change from baseline.
Time frame: Baseline,12, 24 and 36 months
Population: ITT populations: 3 mg group = 394, 2 mg group = 362. Analysis populations (AP) for Month 12: 3 mg group = 381, 2 mg group = 347; Month 24: 3 mg group = 371, 2 mg group = 330; Month 36: 3 mg group = 349, 2 mg group = 314.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Baseline | 0.7651 Percent change | Standard Deviation 0.1035 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Percent Change from Baseline at Month 12 | 0.4487 Percent change | Standard Deviation 2.5604 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Percent Change from Baseline Month 24 | 0.0483 Percent change | Standard Deviation 3.0148 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Percent Change from Baseline at Month 36 | -0.1546 Percent change | Standard Deviation 3.3604 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Percent Change from Baseline at Month 36 | -0.2619 Percent change | Standard Deviation 4.0099 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Baseline | 0.7665 Percent change | Standard Deviation 0.0954 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Percent Change from Baseline Month 24 | -0.049 Percent change | Standard Deviation 3.044 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Mean Total Hip BMD at 12, 24 and 36 Months | Percent Change from Baseline at Month 12 | 0.1258 Percent change | Standard Deviation 3.045 |
Secondary
Relative Percent Change From Baseline in Post-dose Suppression of Serum CTX at 6 Months
Relative percent (%) change from MA17904 baseline of post-dose suppression of serum C-telopeptide crosslinks of type I collagen (CTX) at 6 months- Study MA17904. Percent change=\[(measure at time t - measure at baseline)/measure at baseline\]\*100%, where t= 6 months. The baseline value is used as a reference to calculate the relative change from baseline.
Time frame: Baseline, 6 months
Population: Per-Protocol population: 3 mg group = 363, 2 mg group = 344. Analysis populations (AP) for Month 6: 3 mg group = 89, 2 mg group: 93.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Post-dose Suppression of Serum CTX at 6 Months | Baseline | 0.232 Percent change | Standard Deviation 0.1327 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Post-dose Suppression of Serum CTX at 6 Months | Percent Change from Baseline at Month 6 | -78.024 Percent change | Standard Deviation 18.2619 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Post-dose Suppression of Serum CTX at 6 Months | Baseline | 0.264 Percent change | Standard Deviation 0.1497 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Post-dose Suppression of Serum CTX at 6 Months | Percent Change from Baseline at Month 6 | -81.617 Percent change | Standard Deviation 22.044 |
Secondary
Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months
Relative percent (%) change from baseline of MA17904 and BM16550 (NCT00048074) in serum C-telopeptide crosslinks of type I collagen (CTX) at trough at 6, 12, 24 and 36 months- Study MA17904. Percent change=\[(measure at time t - measure at baseline)/measure at baseline\]\*100%, where t=6, 12, 24 and 36 months. The baseline value is used as a reference to calculate the relative change from baseline.
Time frame: Baseline, 6, 12, 24 and 36 months (i.e., 2.5, 3, 4 and 5 years after initiation of BM16550)
Population: Per-Protocol population: 3 mg group = 363, 2 mg group = 344. Analysis populations (AP) for Month 6: 3 mg group = 87, 2 mg group: 92; Month 12: 3 mg group = 92, 2 mg group = 92; Month 24: 3 mg group = 83, 2 mg group = 85; Month 36: 3 mg group = 75, 2 mg group = 76.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Percent Change from Baseline at Month 6 | 17.562 Percent change | Standard Deviation 64.2113 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Percent Change from Baseline at Month 24 | 42.237 Percent change | Standard Deviation 73.7395 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Percent Change from Baseline at Month 12 | 35.934 Percent change | Standard Deviation 82.8825 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Percent Change from Baseline at Month 36 | 41.478 Percent change | Standard Deviation 67.1965 |
| 2 mg Ibandronate q2mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Baseline | 0.232 Percent change | Standard Deviation 0.1327 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Percent Change from Baseline at Month 36 | 58.478 Percent change | Standard Deviation 160.1702 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Baseline | 0.264 Percent change | Standard Deviation 0.1497 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Percent Change from Baseline at Month 6 | 20.091 Percent change | Standard Deviation 65.696 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Percent Change from Baseline at Month 12 | 34.009 Percent change | Standard Deviation 103.5972 |
| 3 mg Ibandronate q3mo | Relative Percent Change From Baseline in Serum C-telopeptide Crosslinks of Type I Collagen (CTX) at Trough at 6, 12, 24 and 36 Months | Percent Change from Baseline at Month 24 | 47.442 Percent change | Standard Deviation 121.5415 |