Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Bone Density Conservation Agents

All Drugs and Chemicals

Zoledronic Acid

Ibandronic Acid

Participants with multiple myeloma will be randomized to receive ibandronate every 4 weeks for a planned duration of 92 weeks.

Participants with multiple myeloma will be randomized to receive zoledronate every 4 weeks for a planned duration of 92 weeks.

Ibandronate will be administered via 15-minute intravenous (IV) infusion as 6 milligrams (mg) every 4 weeks for 92 weeks.

Ibandronate

Zoledronate will be administered via 15-minute IV infusion as 4 mg every 4 weeks for 92 weeks.

Zoledronate

Clinical Trials

This multicenter, open-label trial will randomize participants with multiple myeloma to a regimen of ibandronate or zoledronate in order to compare the incidence of nephrotoxicity, measured as creatinine clearance (CrCl) reduction greater than (\>) 30 percent (%) or an absolute value of 30 milliliters per minute (mL/min) or lower.

Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Multiple Myeloma

COMPARE: Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Patients With Multiple Myeloma

CrCl was calculated from blood samples using the Cockcroft-Gault formula. Relevant deterioration in renal function was defined as CrCl reduction of 30 percent (%) from Baseline or an absolute value less than or equal to (≤) 30 milliliters per minute (mL/min) at Week 44. The last available value on/before Week 44 was used in the calculation. The percentage of participants with deterioration in renal function at Week 44 was reported.

CrCl was calculated from blood samples using the Cockcroft-Gault formula. Relevant deterioration in renal function was defined as CrCl reduction of 30% from Baseline or an absolute value ≤30 mL/min at Week 92. The last available value on/before Week 92 was used in the calculation. The percentage of participants with deterioration in renal function at Week 92 was reported.

SREs were defined according to the Bondronat Summary of Product Characteristics (SmPC) to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. The percentage of participants with at least 1 SRE during the study was reported.

SREs were defined according to the Bondronat SmPC to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. Time to first SRE was defined as the time from first dose of study drug to the time of SRE during the study. The median time to first SRE was estimated by Kaplan-Meier analysis and expressed in days.

SREs were defined according to the Bondronat SmPC to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. The number of SREs was averaged across all participants, including those participants who did not experience SREs during the study.

The percentage of participants with at least 1 event of osteonecrosis of jaw during the study was reported.

The number of events of osteonecrosis of jaw was averaged across all participants, including those participants who did not experience the event during the study.

The percentage of participants with at least 1 zoledronate dose reduction during the study was reported.

The number of zoledronate dose reductions was averaged across all participants, including those participants who did not have any dose reductions during the study.

The percent change in B-NAG was calculated as \[Week 44 or 92 B-NAG minus Baseline B-NAG\] divided by Baseline B-NAG, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation.

The percent change in A1-microglobulin was calculated as \[Week 44 or 92 A1-microglobulin minus Baseline A1-microglobulin\] divided by Baseline A1-microglobulin, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation.

The percent change in GGT was calculated as \[Week 44 or 92 GGT minus Baseline GGT\] divided by Baseline GGT, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation.

Elevation in SCr was defined as an increase greater than (\>) 0.5 milligrams per deciliter (mg/dL) for participants with Baseline SCr less than (\<) 1.4 mg/dL, or an increase \>1.0 mg/dL for participants with Baseline SCr greater than or equal to (≥) 1.4 mg/dL. For the Week 44 analysis, the last available value on/before Week 44 was used. For the Week 92 analysis, the last available value on/before Week 92 was used. The percentage of participants with elevation of SCr at Weeks 44 and 92 was reported.

CrCl was calculated from blood samples using the Cockcroft-Gault formula, and was also measured by urinalysis. The percent change in CrCl was calculated as \[Week 44 or 92 CrCl minus Baseline CrCl\] divided by Baseline CrCl, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation.

Roche Pharma AG

Hoffmann-La Roche

Safety Population: All participants who received at least one dose of study medication and completed at least one follow-up assessment visit.

Participants with multiple myeloma received ibandronate via 15-minute IV infusion as 6 mg every 4 weeks for up to 92 weeks. As a result of slow recruitment, the treatment duration was shortened to 40 weeks for participants who had not yet received 48 weeks of treatment. All participants returned for an additional follow-up observation 4 weeks after the end of treatment.

Participants with multiple myeloma received zoledronate via 15-minute IV infusion as 4 mg every 4 weeks for up to 92 weeks. As a result of slow recruitment, the treatment duration was shortened to 40 weeks for participants who had not yet received 48 weeks of treatment. All participants returned for an additional follow-up observation 4 weeks after the end of treatment.

Total

Age, Continuous

Sex: Female, Male

Intent-to-Treat (ITT) Population: All participants who were randomized and received at least one dose of study medication and for whom at least one measurement of creatinine clearance (CrCl) was obtained.

The Study was terminated as a result of slow recruitment. At the time of the decision to halt recruitment, the treatment duration was shortened to 40 weeks (instead of 92 weeks) for those participants who had not yet reached Week 48.

Medical Communications

Percentage of Participants With Deterioration in Renal Function According to Reduction in Creatinine Clearance (CrCl) From Baseline to Week 44

Percentage of Participants With Deterioration in Renal Function According to Reduction in CrCl From Baseline to Week 92

Percentage of Participants With Skeletal-Related Events (SREs)

Time to First SRE

Number of SREs for Each Participant

Percentage of Participants With Osteonecrosis of Jaw

Number of Events of Osteonecrosis of Jaw for Each Participant

ITT Population; only the Zoledronate arm was included.

Percentage of Participants With Zoledronate Dose Reduction

Number of Zoledronate Dose Reductions for Each Participant

Week 44

Week 92

ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data for the endpoint.

Percent Change From Baseline in N-Acetyl-Beta-D-Glucosaminidase (B-NAG)

Percent Change From Baseline in Alpha (A) 1-Microglobulin

Percent Change From Baseline in Gamma-Glutamyltransferase (GGT)

Percentage of Participants With Elevation of Serum Creatinine (SCr) From Baseline

Week 44, Calculated/Blood (n=41,40)

Week 44, Measured/Urinalysis (n=37,37)

Week 92, Calculated/Blood (n=41,40)

Week 92, Measured/Urinalysis (n=37,37)

ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data for the endpoint. The number of participants who provided data within the specified timeframe for each analysis (n) is shown in the table.

Percent Change From Baseline in CrCl

Participants with multiple myeloma received ibandronate via 15-minute intravenous (IV) infusion as 6 milligrams (mg) every 4 weeks for up to 92 weeks. As a result of slow recruitment, the treatment duration was shortened to 40 weeks for participants who had not yet received 48 weeks of treatment. All participants returned for an additional follow-up observation 4 weeks after the end of treatment.

Spots Global Cancer Trial Database for Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Multiple Myeloma

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Study Description

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