Osteoporosis Postmenopausal
Conditions
Brief summary
To demonstrate the efficacy/safety of Fosamax Plus D
Interventions
Alendronate sodium/Cholecalciferol; tablet, once weekly, for 16 weeks
DRUGComparator: Alendronate sodium (Fosamax)
Alendronate sodium; tablet, once weekly, for 16 weeks
DIETARY_SUPPLEMENTComparator: Calcium
500 mg oral tablet calcium once daily, for 16 weeks
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient agrees to apply sunscreen and limit sunlight-exposure to 1 hour per day during the study * Patient has been diagnosed with osteoporosis * Patient has been postmenopausal for more than 6 months * Patient has no contraindication to taking oral bisphosphonates * Patient is eligible for dual energy x-ray absorptiometry in spine or hip
Exclusion criteria
* Patients with esophageal dysfunction * Patients who can not sit or stand at least 30 minutes * Patients who had a malignant disease or active systemic disease 5 years prior to participating in this trial * Patients with diseases of bone or mineral metabolism besides osteoporosis or receiving therapies which affect bone metabolism or calcium metabolism * Patients with history of major gastrointestinal disease (peptic ulcer, malabsorption, esophageal disease, gastritis, gastroduodenitis, etc.) within the last 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Below the Deficiency Level (Less Than 15 ng/ml) at 16 Weeks of Treatment | 16 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Serum PTH (Parathyroid Hormone) Percentage Changes From Baseline to 16 Weeks of Treatment | Baseline and 16 weeks |
Participant flow
Recruitment details
17 centers participated in this study (11 - Medical Center of the University, 7 - General Hospital). FPE(First patient enrolled) : March-2008, FPI(First patient in) : April-2008, LPO(Last patient out) : April-2009.
Participants by arm
| Arm | Count |
|---|---|
| Fosamax Plus D Once weekly Fosamax plus D tablet \[Alendronate sodium 70 mg/Cholecalciferol 5600 IU\] + once daily calcium formulation \[500 mg/day\]), 16 weeks | 173 |
| Fosamax Once weekly Fosamax 70 mg tablet \[Alendronate sodium 70 mg\] + once daily calcium formulation \[500 mg/day\]), 16 weeks | 170 |
| Total | 343 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 3 |
| Overall Study | Lost to Follow-up | 5 | 4 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Subject's private reason | 2 | 0 |
| Overall Study | Visit 3, 25 OHD level ≤9 ng/mL | 0 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Fosamax | Fosamax Plus D | Total |
|---|---|---|---|
| A fracture in spine Lumbar 1, Lumbar 2, Lumbar 3, Lumbar 4 and T-score ≤-2.0 | -2.34 T-score STANDARD_DEVIATION 0.3 | -2.44 T-score STANDARD_DEVIATION 0.71 | -2.40 T-score STANDARD_DEVIATION 0.59 |
| Age, Continuous | 65.31 years STANDARD_DEVIATION 7.62 | 64.59 years STANDARD_DEVIATION 7.09 | 64.94 years STANDARD_DEVIATION 7.36 |
| Age, Customized <=44 years of age | 0 participants | 0 participants | 0 participants |
| Age, Customized 45-49 years of age | 0 participants | 1 participants | 1 participants |
| Age, Customized 50-59 years of age | 43 participants | 47 participants | 90 participants |
| Age, Customized 60-69 years of age | 73 participants | 85 participants | 158 participants |
| Age, Customized 70-79 years of age | 51 participants | 37 participants | 88 participants |
| Age, Customized >=80 years of age | 3 participants | 3 participants | 6 participants |
| Diastolic Blood Pressure | 73.82 mm Hg STANDARD_DEVIATION 8.85 | 72.5 mm Hg STANDARD_DEVIATION 8.84 | 73.15 mm Hg STANDARD_DEVIATION 8.86 |
| Femoral neck T-score ≤ -2.5 | -2.94 T-score STANDARD_DEVIATION 0.42 | -2.95 T-score STANDARD_DEVIATION 0.48 | -2.94 T-score STANDARD_DEVIATION 0.45 |
| Femoral total T-score ≤ -2.5 | -3.00 T-score STANDARD_DEVIATION 0.41 | -3.00 T-score STANDARD_DEVIATION 0.52 | -3.00 T-score STANDARD_DEVIATION 0.46 |
| Height | 152.47 Centimeters STANDARD_DEVIATION 5.59 | 152.11 Centimeters STANDARD_DEVIATION 5.88 | 152.29 Centimeters STANDARD_DEVIATION 5.73 |
| Patients with/without Vitamin D deficiency Without Vitamin D deficiency at baseline | 114 participants | 116 participants | 230 participants |
| Patients with/without Vitamin D deficiency With Vitamin D deficiency at baseline | 56 participants | 57 participants | 113 participants |
| serum 25 OHD (Serum 25-hydroxyvitamin D) | 18.71 ng/ml STANDARD_DEVIATION 6.25 | 18.82 ng/ml STANDARD_DEVIATION 6.46 | 18.77 ng/ml STANDARD_DEVIATION 6.35 |
| Serum PTH (Parathyroid hormone) | 23.47 pg/ml STANDARD_DEVIATION 11.85 | 25.27 pg/ml STANDARD_DEVIATION 11.01 | 24.38 pg/ml STANDARD_DEVIATION 11.45 |
| Sex: Female, Male Female | 170 Participants | 173 Participants | 343 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Spine (average of spine Lumbar 1, Lumbar 2, Lumbar 3, Lumbar 4 ) T-score ≤ -2.5 | -3.06 T-score STANDARD_DEVIATION 0.5 | -2.96 T-score STANDARD_DEVIATION 0.4 | -3.01 T-score STANDARD_DEVIATION 0.45 |
| Systolic Blood Pressure | 124.08 mm Hg STANDARD_DEVIATION 14.52 | 122.83 mm Hg STANDARD_DEVIATION 15.8 | 123.45 mm Hg STANDARD_DEVIATION 15.17 |
| T-score classification by inclusion criteria: A fracture in spine Lumbar 1-4 and T-score ≤ -2.0] A fracture in spine Lumbar 1-4 and T-score ≤ -2.0 | 5 Participants | 9 Participants | 14 Participants |
| T-score classification by inclusion criteria: A fracture in spine Lumbar 1-4 and T-score ≤ -2.0] Not Applicable | 165 Participants | 164 Participants | 329 Participants |
| T-score classification by inclusion criteria: Femoral neck T-score ≤ -2.5 Femoral neck T-score ≤ -2.5 | 58 Participants | 43 Participants | 101 Participants |
| T-score classification by inclusion criteria: Femoral neck T-score ≤ -2.5 Not Applicable | 112 Participants | 130 Participants | 242 Participants |
| T-score classification by inclusion criteria: Femoral total T-score ≤ -2.5 Femoral total T-score ≤ -2.5 | 25 Participants | 20 Participants | 45 Participants |
| T-score classification by inclusion criteria: Femoral total T-score ≤ -2.5 Not Applicable | 145 Participants | 153 Participants | 298 Participants |
| T-score classification by inclusion criteria: Spine (average of spine Lumbar 1-4 ) T-score ≤-2.5 Not Applicable | 38 Participants | 29 Participants | 67 Participants |
| T-score classification by inclusion criteria: Spine (average of spine Lumbar 1-4 ) T-score ≤-2.5 Spine (average of spine Lumbar 1-4 ) T-score ≤-2.5 | 132 Participants | 144 Participants | 276 Participants |
| Two or more fractures in spine (Lumbar 1-4) Not Applicable | 166 Participants | 170 Participants | 336 Participants |
| Two or more fractures in spine (Lumbar 1-4) Two or more fractures in spine(Lumbar 1-4) | 4 Participants | 3 Participants | 7 Participants |
| Weight | 54.8 Kilograms STANDARD_DEVIATION 7.03 | 53.84 Kilograms STANDARD_DEVIATION 6.89 | 54.32 Kilograms STANDARD_DEVIATION 6.97 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 60 / 171 | 55 / 170 |
| serious Total, serious adverse events | 7 / 171 | 1 / 170 |
Outcome results
Primary
Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Below the Deficiency Level (Less Than 15 ng/ml) at 16 Weeks of Treatment
Time frame: 16 weeks
Population: Participants for analysis was modified intention to treat (Number of patients : Fosamax Plus D Group was 136, Fosamax was 132). Missing data were imputed by the last observation carried forward (LOCF) technique.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fosamax Plus D | Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Below the Deficiency Level (Less Than 15 ng/ml) at 16 Weeks of Treatment | With Vitamin D Deficiency | 2 participants |
| Fosamax Plus D | Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Below the Deficiency Level (Less Than 15 ng/ml) at 16 Weeks of Treatment | Without Vitamin D Deficiency | 134 participants |
| Fosamax | Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Below the Deficiency Level (Less Than 15 ng/ml) at 16 Weeks of Treatment | With Vitamin D Deficiency | 55 participants |
| Fosamax | Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Below the Deficiency Level (Less Than 15 ng/ml) at 16 Weeks of Treatment | Without Vitamin D Deficiency | 77 participants |
p-value: <0.000195% CI: [0, 0.08]Cochran-Mantel-Haenszel
Secondary
Serum PTH (Parathyroid Hormone) Percentage Changes From Baseline to 16 Weeks of Treatment
Time frame: Baseline and 16 weeks
Population: Participants for analysis was modified intention to treat (Number of patients : Fosamax Plus D Group was 136, Fosamax was 132). Missing data were imputed by the last observation carried forward (LOCF) technique.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Fosamax Plus D | Serum PTH (Parathyroid Hormone) Percentage Changes From Baseline to 16 Weeks of Treatment | 8.17 Percentage Change Serum PTH |
| Fosamax | Serum PTH (Parathyroid Hormone) Percentage Changes From Baseline to 16 Weeks of Treatment | 29.98 Percentage Change Serum PTH |
p-value: 0.0091ANCOVA
Post Hoc
Mean Serum 25 OHD(Serum 25-hydroxyvitamin D) at 16 Weeks of Treatment
Time frame: 16 weeks
Population: Participants for analysis was modified intention to treat (Number of patients : Fosamax Plus D Group was 136, Fosamax was 132). Missing data were imputed by the last observation carried forward (LOCF) technique.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosamax Plus D | Mean Serum 25 OHD(Serum 25-hydroxyvitamin D) at 16 Weeks of Treatment | 30.08 ng/ml | Standard Deviation 5.87 |
| Fosamax | Mean Serum 25 OHD(Serum 25-hydroxyvitamin D) at 16 Weeks of Treatment | 17.14 ng/ml | Standard Deviation 6.04 |
Post Hoc
Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Less and Greater Than 20 ng/ml at 16 Weeks of Treatment
Time frame: 16 weeks
Population: Participants for analysis was modified intention to treat (Number of patients : Fosamax Plus D Group was 136, Fosamax was 132). Missing data were imputed by the last observation carried forward (LOCF) technique.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fosamax Plus D | Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Less and Greater Than 20 ng/ml at 16 Weeks of Treatment | With 25 OHD < 20ng/ml at 16 weeks of treatment | 7 participants |
| Fosamax Plus D | Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Less and Greater Than 20 ng/ml at 16 Weeks of Treatment | With 25 OHD >= 20ng/ml at 16 weeks of treatment | 129 participants |
| Fosamax | Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Less and Greater Than 20 ng/ml at 16 Weeks of Treatment | With 25 OHD < 20ng/ml at 16 weeks of treatment | 93 participants |
| Fosamax | Patients With Serum 25 OHD (Serum 25-hydroxyvitamin D) Less and Greater Than 20 ng/ml at 16 Weeks of Treatment | With 25 OHD >= 20ng/ml at 16 weeks of treatment | 39 participants |
p-value: <0.000195% CI: [0.01, 0.04]Cochran-Mantel-Haenszel