Osteoporosis
Conditions
Brief summary
A study designed to see if the study drug will increase blood levels of vitamin D, bone mineral density (BMD), improve biochemical markers of bone turnover, and reduce the number of falls as compared to women receiving standard care for osteoporosis.
Interventions
DRUGFOSAVANCE 5600 (Alendronate Sodium (+) cholecalciferol)
FOSAVANCE 5600 international units (IU)(Alendronate Sodium 70 mg/Vitamin D 5600 IU) combination tablet once weekly for 6 months (Week 26) during the base period and an additional 6-month extension period (Week 52).
DIETARY_SUPPLEMENTCalcium Supplement 500 mg
Calcium supplied locally by the investigator (containing 500 mg calcium supplement) daily for 52 weeks (unless the patient's dietary intake of calcium exceeds 1000 mg per day).
OTHERReferred-Care Model
Usual treatment for osteoporosis chosen and prescribed by patients' own physicians for 6 months (Week 26) during the base period and an additional 6-month extension period (Week 52).
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female * 65 years or older * Diagnosed with osteoporosis (Bone Mineral Density (BMD) T-score \<= -2.5 at spine or hip) or prior fragility fracture BMD T-score \<=-1.5 in at least one of the anatomic sites including lumbar spine, total hip, and femoral neck sites * Postmenopausal * Low levels of vitamin D as measured 25-hydroxyvitamin D * Has fallen at least once within the past 12 months
Exclusion criteria
* Unable to stand or sit upright for at least 30 minutes * Has a bone disorder other than osteoporosis * Contraindication to the use of FOSAVANCE
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 26 | Week 26 | Percentage of participants with serum levels of 25-hydroxyvitamin D below 20 nanograms/milliliter (ng/mL) after 26 weeks of treatment with FOSAVANCE 5600 once weekly versus Referred-Care in postmenopausal women with osteoporosis and at increased risk of falls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline at Week 26 in Bone-Specific Alkaline Phosphatase | Baseline and Week 26 | Bone-Specific Alkaline Phosphatase (BSAP) is a serum biochemical marker of bone formation and measured in micrograms/Liter (mcg/L). The percent change was calculated as: \[100 \* ((Week 26/Baseline)-1)\]. The greater the percent decrease from baseline, the greater the response to therapy. |
| Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 52 | Week 52 | Percentage of participants with serum levels of 25-hydroxyvitamin D below 20 ng/mL after 52 weeks of treatment (6 month extension study) with FOSAVANCE 5600 once weekly versus Referred-Care in postmenopausal women with osteoporosis and at increased risk of falls. |
| Percent Change From Baseline in Lumbar Spine and Total Hip Bone Mineral Density | Baseline and Week 52 | Bone Mineral Density (BMD) as measured by Dual Energy X-Ray Absorptiometry (DEXA) and measured in g/cm\^2 was obtained at baseline (visit 1) and Week 52 (visit 13) or at early study discontinuation visit. The percent change was calculated as: \[100 \* ((Week 52/Baseline)-1)\]. The greater the percent change from baseline, the greater the response to therapy. |
| Percent Change From Baseline at Week 26 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio | Baseline and Week 26 | N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio (NTx) is a urine biochemical marker of bone resorption and measured in nanomoles (nmol) Bone Collagen Equivalents (BCE)/millimoles (mmol) creatinine. The percent change was calculated as: \[100 \* ((Week 26/Baseline)-1)\]. The greater the percent decrease from baseline, the greater the response to therapy. |
| Percent Change From Baseline at Week 52 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio | Baseline and Week 52 | NTx is a urine biochemical marker of bone resorption and measured in nanomoles (nmol) Bone Collagen Equivalents (BCE)/millimoles (mmol) creatinine. The percent change was calculated as: \[100 \* ((Week 52/Baseline)-1)\]. The greater the percent decrease from baseline, the greater the response to therapy. |
| Percent Change From Baseline at Week 52 in Bone-Specific Alkaline Phosphatase | Baseline and Week 52 | BSAP is a serum biochemical marker of bone formation and measured in micrograms/Liter (mcg/L). The percent change was calculated as: \[100 \* ((Week 52/Baseline)-1)\]. The greater the percent decrease from baseline, the greater the response to therapy. |
| Falls Per Participant | Up to Week 52 | Number of falls per participant was measured. The fall event rate during the study period was defined as the number of adjudicated falls during the study period divided by the total patient-years in the study. Each participant was to be in the study for approximately one year. In order to guide and standardize all procedures during the fall adjudication process, a Standard Operating Procedure for Fall Adjudication was created by the SPONSOR and served as a guideline to standardize operational procedures for fall adjudication. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FOSAVANCE 5600 Alendronate Sodium 70 mg/Vitamin D 5600 I.U. combination tablet once weekly plus a daily 500 mg elemental calcium supplement. | 257 |
| Referred-Care Usual treatment for osteoporosis chosen and prescribed by patients' own physicians. | 258 |
| Total | 515 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 15 | 20 |
Baseline characteristics
| Characteristic | FOSAVANCE 5600 | Referred-Care | Total |
|---|---|---|---|
| Age, Continuous | 72.9 years STANDARD_DEVIATION 5.3 | 72.9 years STANDARD_DEVIATION 5.9 | 72.9 years STANDARD_DEVIATION 5.6 |
| Sex: Female, Male Female | 257 Participants | 258 Participants | 515 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 | 61 / 254 | 70 / 258 |
| serious Total, serious adverse events | 25 / 254 | 29 / 258 |
Outcome results
Primary
Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 26
Percentage of participants with serum levels of 25-hydroxyvitamin D below 20 nanograms/milliliter (ng/mL) after 26 weeks of treatment with FOSAVANCE 5600 once weekly versus Referred-Care in postmenopausal women with osteoporosis and at increased risk of falls.
Time frame: Week 26
Population: Full Analysis Set Population (FAS) included participants who took at least one dose of study therapy during the entire treatment period of FOSAVANCE 5600 or who were~assigned to receive regular care and had data reported at least once post-randomization during the entire study period, and had efficacy measurements during the entire study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOSAVANCE 5600 | Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 26 | 8.6 Percentage of Participants |
| Referred-Care | Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 26 | 31.0 Percentage of Participants |
p-value: <0.00195% CI: [0.12, 0.35]Regression, Logistic
Secondary
Falls Per Participant
Number of falls per participant was measured. The fall event rate during the study period was defined as the number of adjudicated falls during the study period divided by the total patient-years in the study. Each participant was to be in the study for approximately one year. In order to guide and standardize all procedures during the fall adjudication process, a Standard Operating Procedure for Fall Adjudication was created by the SPONSOR and served as a guideline to standardize operational procedures for fall adjudication.
Time frame: Up to Week 52
Population: Intent-to-Treat (ITT) population included all randomized participants within the treatment group to which they were randomized regardless of whether or not a participant may have dropped out in the base or continued into the extension study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FOSAVANCE 5600 | Falls Per Participant | 0.51 Number of Falls | Standard Deviation 1.53 |
| Referred-Care | Falls Per Participant | 0.45 Number of Falls | Standard Deviation 0.8 |
p-value: 0.67595% CI: [-0.12, 0.19]Zero-Inflated Poisson Regression
Secondary
Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 52
Percentage of participants with serum levels of 25-hydroxyvitamin D below 20 ng/mL after 52 weeks of treatment (6 month extension study) with FOSAVANCE 5600 once weekly versus Referred-Care in postmenopausal women with osteoporosis and at increased risk of falls.
Time frame: Week 52
Population: The FAS population included participants who took at least one dose of study therapy during the entire treatment period of FOSAVANCE 5600 or who were assigned to receive regular care and had data reported at least once post-randomization during the entire study period, and had efficacy measurements during the entire study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOSAVANCE 5600 | Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 52 | 11.3 Percentage of Participants |
| Referred-Care | Percentage of Participants With Serum Levels of 25-hydroxyvitamin D Below 20 ng/mL at Week 52 | 36.9 Percentage of Participants |
p-value: <0.00195% CI: [0.13, 0.35]Regression, Logistic
Secondary
Percent Change From Baseline at Week 26 in Bone-Specific Alkaline Phosphatase
Bone-Specific Alkaline Phosphatase (BSAP) is a serum biochemical marker of bone formation and measured in micrograms/Liter (mcg/L). The percent change was calculated as: \[100 \* ((Week 26/Baseline)-1)\]. The greater the percent decrease from baseline, the greater the response to therapy.
Time frame: Baseline and Week 26
Population: Per-Protocol Population: excluded participants due to important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FOSAVANCE 5600 | Percent Change From Baseline at Week 26 in Bone-Specific Alkaline Phosphatase | -46.67 Percent Change |
| Referred-Care | Percent Change From Baseline at Week 26 in Bone-Specific Alkaline Phosphatase | -39.60 Percent Change |
p-value: <0.00195% CI: [-10.95, -3.2]Longitudinal Data Analysis Model
Secondary
Percent Change From Baseline at Week 26 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio
N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio (NTx) is a urine biochemical marker of bone resorption and measured in nanomoles (nmol) Bone Collagen Equivalents (BCE)/millimoles (mmol) creatinine. The percent change was calculated as: \[100 \* ((Week 26/Baseline)-1)\]. The greater the percent decrease from baseline, the greater the response to therapy.
Time frame: Baseline and Week 26
Population: Per-Protocol Population: excluded participants due to important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FOSAVANCE 5600 | Percent Change From Baseline at Week 26 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio | -57.06 Percent Change |
| Referred-Care | Percent Change From Baseline at Week 26 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio | -47.36 Percent Change |
p-value: <0.00195% CI: [-14.49, -4.93]Longitudinal Data Analysis Model
Secondary
Percent Change From Baseline at Week 52 in Bone-Specific Alkaline Phosphatase
BSAP is a serum biochemical marker of bone formation and measured in micrograms/Liter (mcg/L). The percent change was calculated as: \[100 \* ((Week 52/Baseline)-1)\]. The greater the percent decrease from baseline, the greater the response to therapy.
Time frame: Baseline and Week 52
Population: Per-Protocol Population: excluded patients due to important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FOSAVANCE 5600 | Percent Change From Baseline at Week 52 in Bone-Specific Alkaline Phosphatase | -51.21 Percent Change |
| Referred-Care | Percent Change From Baseline at Week 52 in Bone-Specific Alkaline Phosphatase | -43.13 Percent Change |
p-value: <0.00195% CI: [-11.94, -4.21]Longitudinal Data Analysis Model
Secondary
Percent Change From Baseline at Week 52 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio
NTx is a urine biochemical marker of bone resorption and measured in nanomoles (nmol) Bone Collagen Equivalents (BCE)/millimoles (mmol) creatinine. The percent change was calculated as: \[100 \* ((Week 52/Baseline)-1)\]. The greater the percent decrease from baseline, the greater the response to therapy.
Time frame: Baseline and Week 52
Population: Per-Protocol Population: excluded patients due to important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| FOSAVANCE 5600 | Percent Change From Baseline at Week 52 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio | -58.42 Percent Change |
| Referred-Care | Percent Change From Baseline at Week 52 in N-Telopeptides of Type 1 Collagen to Urine Creatinine Ratio | -50.07 Percent Change |
p-value: 0.00195% CI: [-13.19, -3.54]Longitudinal Data Analysis Model
Secondary
Percent Change From Baseline in Lumbar Spine and Total Hip Bone Mineral Density
Bone Mineral Density (BMD) as measured by Dual Energy X-Ray Absorptiometry (DEXA) and measured in g/cm\^2 was obtained at baseline (visit 1) and Week 52 (visit 13) or at early study discontinuation visit. The percent change was calculated as: \[100 \* ((Week 52/Baseline)-1)\]. The greater the percent change from baseline, the greater the response to therapy.
Time frame: Baseline and Week 52
Population: The FAS population included participants who took at least one dose of study therapy during the entire treatment period of FOSAVANCE 5600 or who were assigned to receive regular care and had data reported at least once post-randomization during the entire study period, and had efficacy measurements during the entire study period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| FOSAVANCE 5600 | Percent Change From Baseline in Lumbar Spine and Total Hip Bone Mineral Density | Lumbar Spine (n= 226/ n=219) | 4.92 Percent Change |
| FOSAVANCE 5600 | Percent Change From Baseline in Lumbar Spine and Total Hip Bone Mineral Density | Total Hip (n=227/ n=218) | 2.22 Percent Change |
| Referred-Care | Percent Change From Baseline in Lumbar Spine and Total Hip Bone Mineral Density | Lumbar Spine (n= 226/ n=219) | 3.91 Percent Change |
| Referred-Care | Percent Change From Baseline in Lumbar Spine and Total Hip Bone Mineral Density | Total Hip (n=227/ n=218) | 1.40 Percent Change |
p-value: 0.04795% CI: [0.01, 2]Traditional Longitudinal data analysis
p-value: 0.03595% CI: [0.06, 1.58]Traditional Longitudinal data analysis