DIVA Study - A Study of Different Regimens of Intravenous Administration of Bonviva (Ibandronate) in Women With Post-Menopausal Osteoporosis

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of intravenous administration of Bonviva regimens in women with post-menopausal osteoporosis, compared to oral daily administration. Patients will also receive daily supplementation with vitamin D and calcium. The anticipated time of study treatment is 2+ years, and the target sample size is 500+ individuals.

Official Title
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A Randomized, Double-blind Study Comparing the Effect of Different Treatment Regimens of Intravenous Bonviva on Lumbar Bone Mineral Density in Women With Osteoporosis

Conditions
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Post Menopausal Osteoporosis

Intervention / Treatment
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* Drug: ibandronate [Bonviva/Boniva]
* Drug: ibandronate [Bonviva/Boniva]
* Drug: ibandronate [Bonviva/Boniva]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women 55-80 years of age; post-menopausal for >=5 years; ambulatory. Exclusion Criteria: malignant disease diagnosed within the previous 10 years (except basal cell cancer that has been successfully removed); breast cancer within the previous 20 years; allergy to bisphosphonates; previous treatment with an intravenous bisphosphonate at any time; previous treatment with an oral bisphosphonate within the last 6 months, >1 month of treatment within the last year, or >3 months of treatment within the last 2 years.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: 1<br>oral placebo daily and IV ibandronate 2 mg q 2 mo | Drug: ibandronate [Bonviva/Boniva]<br>* 2mg iv every 2 months<br>|
| Experimental: 2<br>oral ibandronate 2.5 mg daily and IV placebo q 2 mo and q 3 mo | Drug: ibandronate [Bonviva/Boniva]<br>* 2.5mg po daily<br>|
| Experimental: 3<br>oral placebo daily and IV ibandronate 3 mg q 3 mo | Drug: ibandronate [Bonviva/Boniva]<br>* 3mg iv every 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Percent Change From Baseline in Mean Bone Mineral Density (BMD) of Lumbar Spine (L2-L4) at 12 Months | BMD was measured by a single dual-energy x-ray absorptiometry (DXA) scan of the lumbar spine at the time of screening and at Month 12. The change in BMD was defined as the relative difference between the last individual measurement available at 12 months and Baseline, using the following formula: Relative change = 100 x (BMD at 1 year - BMD at Baseline) / (BMD at Baseline) | Baseline and Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Percent Change From Baseline in Mean BMD of Lumbar Spine (L2-L4) at 24 Months | BMD was measured by a single dual-energy x-ray absorptiometry (DXA) scan of the lumbar spine at the time of screening and at Month 24. The change in BMD was defined as the relative difference between the last individual measurement available at 24 months and Baseline, using the following formula: Relative change = 100 x (BMD at 1 year - BMD at Baseline) / (BMD at Baseline) | Baseline and Month 24 | 
| Absolute Change From Baseline in Mean BMD of Lumbar Spine (L2 - L4) at Month 12 and Month 24 | BMD was measured by a single dual-energy x-ray absorptiometry (DXA) scan of the lumbar spine at screening, Month 12 and Month 24. The absolute change from Baseline in mean BMD of the lumbar spine (L2-L4) was defined as the difference between the last individual measurement available at Month 12 or Month 24 and Baseline. Only participants with data available at particular timepoint were analyzed. | Baseline, Month 12 and Month 24 | 
| Relative Percent Change From Baseline in BMD of Proximal Femur (Consisting of Total Hip, Trochanter, and Femoral Neck) at Month 12 and 24 | BMD was measured by a single DXA scan of the proximal femur at the time of screening, Month 12 and Month 24.The change in BMD of the proximal femur (total hip, trochanter, femoral neck) was defined as the relative difference between the last individual measurement available at Month 12 or Month 24and Baseline, using the following formula: Relative change = 100 x (BMD at 1 year/2year - BMD at Baseline) / (BMD at Baseline). BMD of fractured bones that could impact the scan area were not taken into account. Only participants with data available at particular timepoint were analyzed. | Baseline, Month 12 and Month 24 | 
| Absolute Change From Baseline in BMD of Proximal Femur (Consisting of Total Hip, Trochanter, and Femoral Neck) at Month 12 and 24 | BMD was measured by a single DXA scan of the proximal femur at the time of screening, Month 12 and Month 24. The absolute change in BMD was defined as the difference between the last individual measurement available at Month 12 or Month 24 and Baseline. BMD of fractured bones that could impact the scan area were not taken into account. Only participants with data available at particular timepoint were analyzed. | Baseline, Month 12 and Month 24 | 
| Relative Change From Baseline in Serum C-telopeptide of Alpha-chain of Type I Collagen (CTX) at Month 6, 12, and 24 | Serum CTX, a biochemical marker of bone resorption, was measured using the Elecsys s-CTX-I assay, an electrochemiluminescence immunoassay (ECLIA) technique. Samples for serum CTX measurements were collected from participants immediately prior to their IV dosing. Thus, the values reported here represent trough or residual values taken at the end of the 2 month or 3 month IV dosing interval. The change in serum CTX was defined as the relative difference between the last individual measurement available at Month 6 or Month 12 or Month 24 and Baseline, using the following formula: Relative change = 100 x (CTX at Month 6/Month 12/Month 24- CTX at Baseline) / (CTX at Baseline). Only participants with data available at particular timepoint were analyzed. | Baseline, At Month 6, 12, and 24. | 
| Absolute Change From Baseline in Serum CTX at Month 6, 12, and 24 | Serum CTX, a biochemical marker of bone resorption, was measured using the Elecsys s-CTX-I assay, an electrochemiluminescence immunoassay (ECLIA) technique. Samples for serum CTX measurements were collected from participants immediately prior to their IV dosing. Thus, the values reported here represent trough or residual values taken at the end of the 2 month or 3 month IV dosing interval. The absolute change from Baseline in serum CTX was defined as the difference between the last individual measurement available at Month 6 or Month 12 or Month 24 and Baseline. Only participants with data available at particular timepoint were analyzed. | Baseline, At Month 6, 12, and 24. | 
| Percentage of Participants With Mean Lumbar Spine (L2 - L4) BMD Above or Equal to Baseline at Month 12 and 24 | A participant is a responder if the mean lumber spine (L2 - L4) BMD had remained the same or increased above baseline. Only participants with data available at particular timepoint were analyzed. | At Month 12 and 24 | 
| Percentage of Participants With Total Hip BMD Above or Equal to Baseline at Month 12 and 24 | A participant is a responder if the mean total hip BMD had remained the same or increased above baseline. Only participants with data available at particular timepoint were analyzed. | At Month 12 and 24 | 
| Percentage of Participants With Trochanter BMD Above or Equal to Baseline at Month 12 and 24 | A participant is a responder if the mean trochanter BMD had remained the same or increased above baseline. Only participants with data available at particular timepoint were analyzed. | At Month 12 and 24 | 
| Percentage of Participants With Femoral Neck BMD Above or Equal to Baseline at Month 12 and 24 | A participant is a responder if the mean femoral neck BMD had remained the same or increased above baseline. Only participants with data available at particular timepoint were analyzed. | At Month 12 and 24 | 
| Percentage of Participants With Mean Total Hip and Lumbar Spine BMD Above or Equal to Baseline at Month 12 and 24 | A participant is a responder if the mean total hip and mean lumbar spine BMD had remained the same or increased above baseline. Only participants with data available at particular timepoint were analyzed. | At Month 12 and 24 | 
| Percentage of Participants With Mean Trochanter and Lumbar Spine BMD Above or Equal to Baseline at Month 12 and 24 | A participant is a responder if the mean trochanter and lumbar spine BMD had remained the same or increased above baseline. Only participants with data available at particular timepoint were analyzed. | At Month 12 and 24 | 
| Percentage of Participants With Mean Femoral Neck and Lumbar Spine BMD Above or Equal to Baseline at Month 12 and 24 | A participant is a responder if the mean femoral neck and lumbar spine BMD had remained the same or increased above baseline. Only participants with data available at particular timepoint were analyzed. | At Month 12 and 24 | 
| Number of Participants Who Experienced Any Adverse Events (AEs) or Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. | Approximately 2 years | 
| Number of Participants With Any Marked Abnormality in Laboratory Parameters | Marked laboratory test value abnormalities (high and low) are those which exceed the marked reference range (i.e., a reference range greater than the standard reference range) 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: low and high Hematocrit (0.36 - 0.60 fraction), low and high hemoglobin (11.0 - 20.0 g/dL), low and high platelets (100 - 700 * 10^9/L), low and high white blood cell (WBC) (3.0 - 18.0 * 10^9/L), high alanine aminotransferase (ALAT) (0 - 60 U/L), high blood urea nitrogen (BUN) (0 - 14.3 mmol/L) , high creatinine (0 - 154 mmol/L), low albumin (27.0 - 48.0 g/L), low and high chloride (95 - 115 mmol/L), low potassium (3.0 - 6.0 mmol/L), low sodium (130 - 150 mmol/L), high calcium (2.00 - 2.90 mmol/L), low and high phosphate (0.75 - 1.60 mmol/L). | Approximately 2 years |