A Study of Bone Turnover Markers in Post-Menopausal Women With Osteoporosis Treated With Monthly Boniva (Ibandronate)

Study Overview
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Brief Summary
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This study will determine the rapidity of suppression of the bone resorption marker sCTX in post-menopausal women with osteoporosis.Other bone turnover markers will also be evaluated. Patients will be randomised to either monthly Boniva 150mg or placebo, in combination with vitamin D and calcium supplementation. The anticipated time on study treatment is approximately 7 months, and the target sample size is <100 individuals.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Determine Time to Onset of Suppression of the Bone Resorption Marker sCTX With Once Monthly Ibandronate in the Treatment of Postmenopausal Osteoporosis

Conditions
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Post Menopausal Osteoporosis

Intervention / Treatment
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* Drug: Placebo
* Drug: Vitamin D and calcium supplementation
* Drug: ibandronate [Bonviva/Boniva]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women who have been newly diagnosed with post-menopausal osteoporosis, requiring treatment; naive to bisphosphonate treatment,or had bisphosphonate treatment for a maximum of 3 months, at least 5 years before screening. Exclusion Criteria: patients on hormone replacement therapy (HRT) within the last 3 months; patients on other osteoporosis medication within the last 3 months; sCTX below lower limit, or above 3 times the upper limit, of normal premenopausal level; hypersensitivity to any component of ibandronate; contraindication for calcium or vitamin D therapy; history of major gastrointestinal upset; malignant disease diagnosed within the previous 10 years (except resected basal cell cancer).

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibandronate<br>Participants received Ibandronate 150 mg tablet once-monthly along with a combination dietary supplement containing vitamin D 200 international units (IU) and elemental calcium 500 mg twice daily with meals for 6 months. | Drug: Vitamin D and calcium supplementation<br>* As prescribed<br>Drug: ibandronate [Bonviva/Boniva]<br>* 150mg po monthly for 6 months<br>|
| Placebo Comparator: Placebo<br>Participants received a matching placebo tablet to Ibandronate once-monthly along with a combination dietary supplement containing vitamin D 200 IU and elemental calcium 500 mg twice daily with meals for 6 months. | Drug: Placebo<br>* po monthly for 6 months<br>Drug: Vitamin D and calcium supplementation<br>* As prescribed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Percent Change in Serum C-terminal Telopeptide of Type 1 Collagen Concentration (sCTX) From Baseline to Day 3 | Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. It is measured in units of nanograms (ng) per milliliter (mL). The relative change in sCTX was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (sCTX time point- sCTX Baseline) / (sCTX Baseline) * 100. The sCTX value used for Baseline was the average of the results from the 2 blood samples taken at screening. If 1 of these 2 samples was nonquantifiable or missing, then the Baseline sCTX was the result from the non-missing sample. Baseline visit was defined as Visit 1. | Baseline (Visit 1) and Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Percent Change in Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) Concentration From Baseline Over Time | sCTX is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. The relative change in sCTX was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (sCTX Time point- sCTX Baseline) / (sCTX Baseline) * 100. The sCTX value used for Baseline was the average of the results from the 2 blood samples taken at screening. If 1 of these 2 samples was nonquantifiable or missing, then the Baseline sCTX was the result from the non-missing sample. Baseline visit was defined as Visit 1. | Baseline (Visit 1), Day (D) 3, D7, D14, D21, D28 of Month (M)1, M2, M3, M4, M5, M6 | 
| Relative Percent Change in Bone Specific Alkaline Phosphatase (BSAP) Concentration From Baseline Over Time | BSAP is a biochemical marker of bone formation and measured in units per litre (U/L). The relative percent change in BSAP was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (BSAP time point- BSAP Baseline) / (BSAP Baseline) * 100. The greater the percent decrease from Baseline, the greater the response to therapy. Baseline visit was defined as Visit 1. | Baseline (Visit 1), Day (D) 7 and D 28 of Month (M)1, M2, M3, M4, M5, M6 | 
| Relative Percent Change in Parathyroid Hormone (PTH) From Baseline to Post Treatment Assessments | Parathyroid hormone (PTH) regulates calcium and phosphate metabolism in bone and kidney, and is measured in picogram/milliliter (pg/mL). The relative percent change in PTH was defined as the relative difference between the value at each time point and the value at Baseline, using the following formula: Relative change = (PTH time point- PTH Baseline) / (PTH Baseline) * 100. Post treatment assessments were done at Baseline, Month (M)1 Day (D)7, and M6D7 | Baseline (Visit 1), Month (M)1 Day (D)7, and M6D7 | 
| Percentage of Participants With a Serum C-terminal Telopeptide of Type1 Collagen (sCTX) Concentration Between 0.011 and 0.631 ng/mL and Who Have Achieved a Decrease in sCTX Concentration of at Least 8 Percent | The Cochran-Mantel Haenszel test stratified by Baseline sCTX category was used to compare the 2 treatment groups for proportion of participants whose sCTX concentration was between 0.011 and 0.631 ng/mL (premenopausal normal range mean +/- 2 SD) who achieved a decrease in sCTX of at least 8% from Baseline. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD=0.155 ng/mL. Baseline visit was defined as Visit 1. | Baseline (Visit 1) and Day (D)3 of Month (M)1 and; D7, D14, D21, D28 of each M1, M2, M3, M4, M5, and M6 | 
| Percentage of Participants With a Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) Concentration Between 0.011 and 0.476 ng/mL | Percentage of participants whose sCTX concentration was between 0.011 and 0.476 ng/mL (Mean -2 to + 1 SD) were analyzed at particular time points. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD = 0.155 ng/mL. Baseline visit was defined as Visit 1. | Baseline (Visit 1) and Day (D)3 of M1 and D7, D14, D21, D28 of each M1, M2, M3, M4, M5, M6 | 
| Percentage of Participants With a Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) Concentration Between 0.011 and 0.321 ng/mL | Percentage of participants whose sCTX concentration was between 0.011 and 0.321 ng/mL (Mean -2 to + 0 SD) were analyzed at particular time points. Mean and SD are based on the normal range for premenopausal women: Mean = 0.321 ng/mL, SD = 0.155 ng/mL. | Baseline (Visit 1), Day (D)3 of M1, and D7, D14, D21, D28 of each M1, M2, M3, M4, M5, M6 | 
| Difference Between the Minimum and Maximum Relative Percent Change in Serum C-terminal Telopeptide of Type 1 Collagen (sCTX) Concentrations | Overall minimum and maximum relative percent change in sCTX concentrations from Baseline were calculated for all participants over D7, D14, D21 and D28 of Month 6 and the difference between it was analyzed. | Day (D)7, D14, D21 and D28 of Month 6 | 
| Number of Participants With Any Marked Abnormality in Laboratory Parameters | Marked laboratory abnormalities are those which exceed the marked abnormality range (i.e., greater or less than the Roche defined marked abnormality range; i.e Low or High) and which also represents a clinically relevant change from Baseline of at least a designated amount. The indicated abnormal laboratory parameters (along with their marked reference range) are as follows : Hematocrit (0.31- 0.56 fraction), hemoglobin (110 - 200 g/L), platelets (100 - 550 *10^9/L), white blood cell (WBC) (3.0 - 18.0 *10^9/L), alanine aminotransferase (ALT) (0 - 110 U/L), creatinine (0 - 154 µmol/L), chloride (95 - 115 mmol/L), phosphate (0.75 - 1.60 mmol/L ). Creatinine clearance was calculated using the Cockroft-Gault formula. | Up to 7 months | 
| Number of Participants With Any Adverse Event or Serious Adverse Event | An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. | Up to 7 months |