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

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

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.

Study Overview

• Status: Completed
• Conditions: Post Menopausal Osteoporosis
• Intervention / Treatment: Drug: ibandronate [Bonviva/Boniva]; Drug: ibandronate [Bonviva/Boniva]; Drug: ibandronate [Bonviva/Boniva]

• Study Type: Interventional
• Enrollment (Actual): 1395
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Darlinghurst, Australia, 2010
  • Melbourne, Australia, 3084
  • Nedlands, Australia, 6000
  • St. Leonards, Australia, 2139
  • Sydney, Australia, 3129
• Belgium
  • Bruxelles, Belgium, 1180
  • Liege, Belgium, 4020
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5C 2T2
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
    • Montreal, Quebec, Canada, H3A 1A1
    • Montreal, Quebec, Canada, H2X 3J4
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
• Czech Republic
  • Plzen, Czech Republic, 305 99
  • Praha, Czech Republic, 128 00
• Denmark
  • Aalborg, Denmark, 9000
  • Ballerup, Denmark, 2750
  • København, Denmark, 1399
  • Vejle, Denmark, 7100
  • Århus, Denmark, 8000
• France
  • Lyon, France, 69437
  • Orleans, France, 45000
• Germany
  • Berlin, Germany, 12200
  • Bochum, Germany, 44789
  • Hamburg, Germany, 20246
• Hungary
  • Budapest, Hungary, 1036
• Italy
  • Arenzano, Italy, 16011
  • Siena, Italy, 53100
  • Valeggio Sul Mincio, Italy, 37067
• Mexico
  • Mexico City, Mexico, 11000
  • Monterrey, Mexico, 64460
• Norway
  • Haugesund, Norway, 5507
  • Oslo, Norway, 0176
  • Stavanger, Norway, 4010
• Poland
  • Grudziadz, Poland, 86-300
  • Krakow, Poland, 31-501
  • Krakow, Poland, 30-510
• South Africa
  • Cape Town, South Africa, 7500
  • Pretoria, South Africa
  • Sommerset West, South Africa, 7129
• Spain
  • Barcelona, Spain, 08003
  • Madrid, Spain, 28046
  • Santander, Spain, 39008
• United Kingdom
  • Aberdeen, United Kingdom, AB25 1LD
  • Manchester, United Kingdom, M13 9WL
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-7199
  • California
    • Irvine, California, United States, 92618
    • Rancho Mirage, California, United States, 92270
  • Florida
    • Leesburg, Florida, United States, 34748
  • Georgia
    • Gainesville, Georgia, United States, 30501
  • Idaho
    • Coeur D'alene, Idaho, United States, 83814
  • Maryland
    • Bethesda, Maryland, United States, 20817
  • Missouri
    • St Louis, Missouri, United States, 63110
  • Montana
    • Billings, Montana, United States, 59120
  • Nebraska
    • Omaha, Nebraska, United States, 68131
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
  • New York
    • New York, New York, United States, 10029
  • North Dakota
    • Bismarck, North Dakota, United States, 58503
    • Fargo, North Dakota, United States, 58103
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
  • Texas
    • San Antonio, Texas, United States, 78229
  • Virginia
    • Virginia Beach, Virginia, United States, 23462
  • Wisconsin
    • Madison, Wisconsin, United States, 53792

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; oral placebo daily and IV ibandronate 2 mg q 2 mo	Drug: ibandronate [Bonviva/Boniva]; 3mg iv every 3 months; Drug: ibandronate [Bonviva/Boniva]; 2mg iv every 2 months; Drug: ibandronate [Bonviva/Boniva]; 2.5mg po daily
Experimental: 2; oral ibandronate 2.5 mg daily and IV placebo q 2 mo and q 3 mo	Drug: ibandronate [Bonviva/Boniva]; 3mg iv every 3 months; Drug: ibandronate [Bonviva/Boniva]; 2mg iv every 2 months; Drug: ibandronate [Bonviva/Boniva]; 2.5mg po daily
Experimental: 3; oral placebo daily and IV ibandronate 3 mg q 3 mo	Drug: ibandronate [Bonviva/Boniva]; 3mg iv every 3 months; Drug: ibandronate [Bonviva/Boniva]; 2mg iv every 2 months; Drug: ibandronate [Bonviva/Boniva]; 2.5mg po daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Bianchi G, Czerwinski E, Kenwright A, Burdeska A, Recker RR, Felsenberg D. Long-term administration of quarterly IV ibandronate is effective and well tolerated in postmenopausal osteoporosis: 5-year data from the DIVA study long-term extension. Osteoporos Int. 2012 Jun;23(6):1769-78. doi: 10.1007/s00198-011-1793-9.

Study record dates

Study Major Dates

• Study Start: June 1, 2002
• Primary Completion (Actual): May 1, 2005
• Study Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: October 24, 2002
• First Submitted That Met QC Criteria: October 24, 2002
• First Posted (Estimate): October 25, 2002

Study Record Updates

• Last Update Posted (Estimate): February 3, 2016
• Last Update Submitted That Met QC Criteria: January 4, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; Physiological Effects of Drugs; Bone Density Conservation Agents; Ibandronic Acid
• Other Study ID Numbers: BM16550