COMPARE: Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Multiple Myeloma
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Ibandronate Participants with multiple myeloma will be randomized to receive ibandronate every 4 weeks for a planned duration of 92 weeks. |
Drug: Ibandronate
Ibandronate will be administered via 15-minute intravenous (IV) infusion as 6 milligrams (mg) every 4 weeks for 92 weeks.
Other Names:
|
Active Comparator: Zoledronate Participants with multiple myeloma will be randomized to receive zoledronate every 4 weeks for a planned duration of 92 weeks. |
Drug: Zoledronate
Zoledronate will be administered via 15-minute IV infusion as 4 mg every 4 weeks for 92 weeks.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Deterioration in Renal Function According to Reduction in Creatinine Clearance (CrCl) From Baseline to Week 44 [Baseline, Week 44]
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.
- Percentage of Participants With Deterioration in Renal Function According to Reduction in CrCl From Baseline to Week 92 [Baseline, Week 92]
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.
Secondary Outcome Measures
- Percentage of Participants With Skeletal-Related Events (SREs) [From Baseline to end of study (up to Week 96)]
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.
- Time to First SRE [From Baseline to end of study (up to Week 96)]
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.
- Number of SREs for Each Participant [From Baseline to end of study (up to Week 96)]
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.
- Percentage of Participants With Osteonecrosis of Jaw [From Baseline to end of study (up to Week 96)]
The percentage of participants with at least 1 event of osteonecrosis of jaw during the study was reported.
- Number of Events of Osteonecrosis of Jaw for Each Participant [From Baseline to end of study (up to Week 96)]
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.
- Percentage of Participants With Zoledronate Dose Reduction [From Baseline to end of study (up to Week 96)]
The percentage of participants with at least 1 zoledronate dose reduction during the study was reported.
- Number of Zoledronate Dose Reductions for Each Participant [From Baseline to end of study (up to Week 96)]
The number of zoledronate dose reductions was averaged across all participants, including those participants who did not have any dose reductions during the study.
- Percent Change From Baseline in N-Acetyl-Beta-D-Glucosaminidase (B-NAG) [Baseline and Weeks 44, 92]
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.
- Percent Change From Baseline in Alpha (A) 1-Microglobulin [Baseline and Weeks 44, 92]
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.
- Percent Change From Baseline in Gamma-Glutamyltransferase (GGT) [Baseline and Weeks 44, 92]
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.
- Percentage of Participants With Elevation of Serum Creatinine (SCr) From Baseline [Baseline and Weeks 44, 92]
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.
- Percent Change From Baseline in CrCl [Baseline and Weeks 44, 92]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Confirmed multiple myeloma, Stage II-III as per Salmon and Durie (1975)
-
Indication for biphosphonate therapy
Exclusion Criteria:
-
Previous therapy with ibandronate or zoledronate within the past 12 months
-
Renal insufficiency with serum creatinine >3.0 mg/dL or >265 micromoles per liter (µmol/L) or CrCl <30 mL/min
-
Hypersensitivity to ibandronate, zoledronate, or other biphosphonates
-
Presence of secondary malignomas, apart from basaliomas and cervical carcinoma in situ
-
Severe accompanying illness with organ impairment
-
Osteonecrosis of the jaw at the start of the study
-
Life expectancy ≤12 months
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Ansbach | Germany | 91522 | ||
2 | Aschaffenburg | Germany | 63739 | ||
3 | Augsburg | Germany | 86150 | ||
4 | Berlin | Germany | 10437 | ||
5 | Berlin | Germany | 10707 | ||
6 | Berlin | Germany | 12627 | ||
7 | Bremen | Germany | 28239 | ||
8 | Duisburg | Germany | 47051 | ||
9 | Duisburg | Germany | 47166 | ||
10 | Erlangen | Germany | 91054 | ||
11 | Essen | Germany | 45136 | ||
12 | Esslingen | Germany | 73730 | ||
13 | Frankfurt Am Main | Germany | 60389 | ||
14 | Frankfurt Am Main | Germany | 65929 | ||
15 | Greifswald | Germany | 17475 | ||
16 | Göttingen | Germany | 37075 | ||
17 | Güstrow | Germany | 18273 | ||
18 | Gütersloh | Germany | 33332 | ||
19 | Halle | Germany | 06110 | ||
20 | Hamburg | Germany | 22081 | ||
21 | Hamburg | Germany | 22457 | ||
22 | Hamm | Germany | 59063 | ||
23 | Hannover | Germany | 30171 | ||
24 | Hannover | Germany | 30625 | ||
25 | Herne | Germany | 44625 | ||
26 | Hof | Germany | 95028 | ||
27 | Jena | Germany | 07743 | ||
28 | Karlsruhe | Germany | 76137 | ||
29 | Kassel | Germany | 34117 | ||
30 | Kassel | Germany | 34125 | ||
31 | Koblenz | Germany | 56068 | ||
32 | Krefeld | Germany | 47798 | ||
33 | Köln | Germany | 50677 | ||
34 | Köln | Germany | 50924 | ||
35 | Leer | Germany | 26789 | ||
36 | Leipzig | Germany | 04289 | ||
37 | Ludwigshafen | Germany | 67063 | ||
38 | Lübeck | Germany | 23562 | ||
39 | Magedburg | Germany | 39104 | ||
40 | Minden | Germany | 32427 | ||
41 | Moers | Germany | 47441 | ||
42 | Muenster | Germany | 48149 | ||
43 | Mülheim | Germany | 45468 | ||
44 | München | Germany | 80336 | ||
45 | Neumünster | Germany | 24534 | ||
46 | Offenbach | Germany | 63069 | ||
47 | Offenburg | Germany | 77652 | ||
48 | Oldenburg | Germany | 26121 | ||
49 | Oldenburg | Germany | 26133 | ||
50 | Stuttgart | Germany | 70174 | ||
51 | Stuttgart | Germany | 70199 | ||
52 | Tübingen | Germany | 72076 | ||
53 | Weiden | Germany | 92637 | ||
54 | Wiesbaden | Germany | 65191 | ||
55 | Würzburg | Germany | 97080 | ||
56 | Zwickau | Germany | 08058 |
Sponsors and Collaborators
- Hoffmann-La Roche
- Roche Pharma AG
Investigators
- Study Chair: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ML18508
- 2005-003264-38
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. | 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. |
Period Title: Overall Study | ||
STARTED | 46 | 43 |
Completed at Week 44 | 11 | 5 |
Completed at Week 96 | 10 | 10 |
COMPLETED | 21 | 15 |
NOT COMPLETED | 25 | 28 |
Baseline Characteristics
Arm/Group Title | Ibandronate | Zoledronate | Total |
---|---|---|---|
Arm/Group Description | 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 of all reporting groups |
Overall Participants | 41 | 40 | 81 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
65.3
(9.4)
|
69.1
(9.1)
|
67.2
(9.4)
|
Sex: Female, Male (Count of Participants) | |||
Female |
15
36.6%
|
14
35%
|
29
35.8%
|
Male |
26
63.4%
|
26
65%
|
52
64.2%
|
Outcome Measures
Title | Percentage of Participants With Deterioration in Renal Function According to Reduction in Creatinine Clearance (CrCl) From Baseline to Week 44 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 44 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-Treat (ITT) Population. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Number (95% Confidence Interval) [percentage of participants] |
9.8
23.9%
|
12.5
31.3%
|
Title | Percentage of Participants With Deterioration in Renal Function According to Reduction in CrCl From Baseline to Week 92 |
---|---|
Description | 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. |
Time Frame | Baseline, Week 92 |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Number (95% Confidence Interval) [percentage of participants] |
14.6
35.6%
|
12.5
31.3%
|
Title | Percentage of Participants With Skeletal-Related Events (SREs) |
---|---|
Description | 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. |
Time Frame | From Baseline to end of study (up to Week 96) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Number (95% Confidence Interval) [percentage of participants] |
22.0
53.7%
|
30.0
75%
|
Title | Time to First SRE |
---|---|
Description | 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. |
Time Frame | From Baseline to end of study (up to Week 96) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Median (Full Range) [days] |
393.0
|
244.5
|
Title | Number of SREs for Each Participant |
---|---|
Description | 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. |
Time Frame | From Baseline to end of study (up to Week 96) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Mean (Standard Deviation) [SREs] |
0.3
(0.6)
|
0.5
(1.1)
|
Title | Percentage of Participants With Osteonecrosis of Jaw |
---|---|
Description | The percentage of participants with at least 1 event of osteonecrosis of jaw during the study was reported. |
Time Frame | From Baseline to end of study (up to Week 96) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Number (95% Confidence Interval) [percentage of participants] |
0.0
0%
|
0.0
0%
|
Title | Number of Events of Osteonecrosis of Jaw for Each Participant |
---|---|
Description | 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. |
Time Frame | From Baseline to end of study (up to Week 96) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Mean (Standard Deviation) [events of osteonecrosis of jaw] |
0.0
(0.0)
|
0.0
(0.0)
|
Title | Percentage of Participants With Zoledronate Dose Reduction |
---|---|
Description | The percentage of participants with at least 1 zoledronate dose reduction during the study was reported. |
Time Frame | From Baseline to end of study (up to Week 96) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population; only the Zoledronate arm was included. |
Arm/Group Title | Zoledronate |
---|---|
Arm/Group Description | 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. |
Measure Participants | 40 |
Number (95% Confidence Interval) [percentage of participants] |
30.0
73.2%
|
Title | Number of Zoledronate Dose Reductions for Each Participant |
---|---|
Description | The number of zoledronate dose reductions was averaged across all participants, including those participants who did not have any dose reductions during the study. |
Time Frame | From Baseline to end of study (up to Week 96) |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population; only the Zoledronate arm was included. |
Arm/Group Title | Zoledronate |
---|---|
Arm/Group Description | 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. |
Measure Participants | 40 |
Mean (Standard Deviation) [dose reductions] |
0.8
(1.4)
|
Title | Percent Change From Baseline in N-Acetyl-Beta-D-Glucosaminidase (B-NAG) |
---|---|
Description | 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. |
Time Frame | Baseline and Weeks 44, 92 |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data for the endpoint. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 38 | 37 |
Week 44 |
-15.7
|
10.6
|
Week 92 |
-17.2
|
9.3
|
Title | Percent Change From Baseline in Alpha (A) 1-Microglobulin |
---|---|
Description | 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. |
Time Frame | Baseline and Weeks 44, 92 |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data for the endpoint. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 38 | 37 |
Week 44 |
0.0
|
0.0
|
Week 92 |
0.0
|
0.0
|
Title | Percent Change From Baseline in Gamma-Glutamyltransferase (GGT) |
---|---|
Description | 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. |
Time Frame | Baseline and Weeks 44, 92 |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. The "Number of Participants Analyzed" reflects the total number of participants who provided evaluable data for the endpoint. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 38 | 37 |
Week 44 |
-6.0
|
3.8
|
Week 92 |
-2.5
|
3.8
|
Title | Percentage of Participants With Elevation of Serum Creatinine (SCr) From Baseline |
---|---|
Description | 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. |
Time Frame | Baseline and Weeks 44, 92 |
Outcome Measure Data
Analysis Population Description |
---|
ITT Population. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Week 44 |
2.4
5.9%
|
2.5
6.3%
|
Week 92 |
7.3
17.8%
|
2.5
6.3%
|
Title | Percent Change From Baseline in CrCl |
---|---|
Description | 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. |
Time Frame | Baseline and Weeks 44, 92 |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Ibandronate | Zoledronate |
---|---|---|
Arm/Group Description | 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. |
Measure Participants | 41 | 40 |
Week 44, Calculated/Blood (n=41,40) |
-0.5
(28.5)
|
-0.4
(21.7)
|
Week 44, Measured/Urinalysis (n=37,37) |
6.9
(53.0)
|
3.9
(37.3)
|
Week 92, Calculated/Blood (n=41,40) |
-0.7
(31.9)
|
-4.3
(20.3)
|
Week 92, Measured/Urinalysis (n=37,37) |
3.1
(45.6)
|
2.0
(39.1)
|
Adverse Events
Time Frame | From Baseline to end of study (up to Week 96) | |||
---|---|---|---|---|
Adverse Event Reporting Description | Safety Population: All participants who received at least one dose of study medication and completed at least one follow-up assessment visit. | |||
Arm/Group Title | Ibandronate | Zoledronate | ||
Arm/Group Description | 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. | ||
All Cause Mortality |
||||
Ibandronate | Zoledronate | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Ibandronate | Zoledronate | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 27/46 (58.7%) | 18/43 (41.9%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 0/46 (0%) | 1/43 (2.3%) | ||
Febrile neutropenia | 1/46 (2.2%) | 0/43 (0%) | ||
Normochromic normocytic anaemia | 0/46 (0%) | 1/43 (2.3%) | ||
Pancytopenia | 1/46 (2.2%) | 0/43 (0%) | ||
Thrombocytopenia | 1/46 (2.2%) | 0/43 (0%) | ||
Cardiac disorders | ||||
Arrhythmia | 1/46 (2.2%) | 0/43 (0%) | ||
Atrial fibrillation | 1/46 (2.2%) | 0/43 (0%) | ||
Cardiac failure | 1/46 (2.2%) | 1/43 (2.3%) | ||
Myocardial infarction | 0/46 (0%) | 1/43 (2.3%) | ||
Gastrointestinal disorders | ||||
Diarrhoea | 2/46 (4.3%) | 0/43 (0%) | ||
Diverticulum | 1/46 (2.2%) | 0/43 (0%) | ||
Enteritis | 0/46 (0%) | 1/43 (2.3%) | ||
Gastrointestinal haemorrhage | 1/46 (2.2%) | 0/43 (0%) | ||
Vomiting | 1/46 (2.2%) | 0/43 (0%) | ||
General disorders | ||||
Asthenia | 1/46 (2.2%) | 0/43 (0%) | ||
General physical health deterioration | 2/46 (4.3%) | 0/43 (0%) | ||
Pyrexia | 2/46 (4.3%) | 0/43 (0%) | ||
Infections and infestations | ||||
Abscess oral | 0/46 (0%) | 1/43 (2.3%) | ||
Bronchitis | 1/46 (2.2%) | 0/43 (0%) | ||
Bronchopneumonia | 1/46 (2.2%) | 0/43 (0%) | ||
Gastroenteritis | 1/46 (2.2%) | 0/43 (0%) | ||
Herpes zoster | 1/46 (2.2%) | 0/43 (0%) | ||
Implant site infection | 1/46 (2.2%) | 1/43 (2.3%) | ||
Infection | 3/46 (6.5%) | 0/43 (0%) | ||
Pneumocystis jiroveci pneumonia | 0/46 (0%) | 1/43 (2.3%) | ||
Pneumonia | 4/46 (8.7%) | 1/43 (2.3%) | ||
Septic shock | 2/46 (4.3%) | 1/43 (2.3%) | ||
Urosepsis | 1/46 (2.2%) | 0/43 (0%) | ||
Injury, poisoning and procedural complications | ||||
Fracture | 0/46 (0%) | 1/43 (2.3%) | ||
Humerus fracture | 0/46 (0%) | 1/43 (2.3%) | ||
Lumbar vertebral fracture | 1/46 (2.2%) | 0/43 (0%) | ||
Post procedural swelling | 1/46 (2.2%) | 0/43 (0%) | ||
Investigations | ||||
Blood creatinine increased | 3/46 (6.5%) | 1/43 (2.3%) | ||
Creatinine renal clearance decreased | 2/46 (4.3%) | 4/43 (9.3%) | ||
Metabolism and nutrition disorders | ||||
Decreased appetite | 1/46 (2.2%) | 0/43 (0%) | ||
Diabetes mellitus | 1/46 (2.2%) | 0/43 (0%) | ||
Hyperglycaemia | 1/46 (2.2%) | 1/43 (2.3%) | ||
Hypokalaemia | 1/46 (2.2%) | 0/43 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Back pain | 1/46 (2.2%) | 0/43 (0%) | ||
Bone pain | 2/46 (4.3%) | 0/43 (0%) | ||
Intervertebral disc compression | 0/46 (0%) | 1/43 (2.3%) | ||
Musculoskeletal chest pain | 1/46 (2.2%) | 0/43 (0%) | ||
Pathological fracture | 1/46 (2.2%) | 0/43 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Multiple myeloma | 4/46 (8.7%) | 0/43 (0%) | ||
Neoplasm progression | 1/46 (2.2%) | 0/43 (0%) | ||
Plasmacytoma | 1/46 (2.2%) | 0/43 (0%) | ||
Nervous system disorders | ||||
Dizziness | 1/46 (2.2%) | 0/43 (0%) | ||
Paraplegia | 0/46 (0%) | 1/43 (2.3%) | ||
Syncope | 1/46 (2.2%) | 1/43 (2.3%) | ||
Renal and urinary disorders | ||||
Nephropathy toxic | 0/46 (0%) | 1/43 (2.3%) | ||
Renal failure | 1/46 (2.2%) | 0/43 (0%) | ||
Renal failure acute | 1/46 (2.2%) | 0/43 (0%) | ||
Renal failure chronic | 1/46 (2.2%) | 0/43 (0%) | ||
Renal impairment | 0/46 (0%) | 1/43 (2.3%) | ||
Urinary retention | 0/46 (0%) | 1/43 (2.3%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Bronchial haemorrhage | 1/46 (2.2%) | 0/43 (0%) | ||
Dyspnoea | 0/46 (0%) | 1/43 (2.3%) | ||
Pleural effusion | 1/46 (2.2%) | 0/43 (0%) | ||
Pulmonary embolism | 1/46 (2.2%) | 0/43 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Skin haemorrhage | 0/46 (0%) | 1/43 (2.3%) | ||
Vascular disorders | ||||
Circulatory collapse | 1/46 (2.2%) | 0/43 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Ibandronate | Zoledronate | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 43/46 (93.5%) | 34/43 (79.1%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 11/46 (23.9%) | 11/43 (25.6%) | ||
Leukopenia | 10/46 (21.7%) | 7/43 (16.3%) | ||
Thrombocytopenia | 6/46 (13%) | 3/43 (7%) | ||
Ear and labyrinth disorders | ||||
Vertigo | 3/46 (6.5%) | 2/43 (4.7%) | ||
Gastrointestinal disorders | ||||
Diarrhoea | 10/46 (21.7%) | 8/43 (18.6%) | ||
Nausea | 6/46 (13%) | 9/43 (20.9%) | ||
Constipation | 4/46 (8.7%) | 4/43 (9.3%) | ||
Vomiting | 4/46 (8.7%) | 1/43 (2.3%) | ||
Dry mouth | 1/46 (2.2%) | 3/43 (7%) | ||
General disorders | ||||
Oedema peripheral | 7/46 (15.2%) | 10/43 (23.3%) | ||
Fatigue | 7/46 (15.2%) | 7/43 (16.3%) | ||
Pyrexia | 6/46 (13%) | 7/43 (16.3%) | ||
Pain | 4/46 (8.7%) | 4/43 (9.3%) | ||
Chills | 1/46 (2.2%) | 3/43 (7%) | ||
Chest pain | 0/46 (0%) | 3/43 (7%) | ||
General physical health deterioration | 3/46 (6.5%) | 0/43 (0%) | ||
Infections and infestations | ||||
Nasopharyngitis | 19/46 (41.3%) | 10/43 (23.3%) | ||
Bronchitis | 8/46 (17.4%) | 3/43 (7%) | ||
Candidiasis | 4/46 (8.7%) | 5/43 (11.6%) | ||
Herpes zoster | 2/46 (4.3%) | 7/43 (16.3%) | ||
Influenza | 4/46 (8.7%) | 2/43 (4.7%) | ||
Pneumonia | 3/46 (6.5%) | 0/43 (0%) | ||
Urinary tract infection | 3/46 (6.5%) | 0/43 (0%) | ||
Metabolism and nutrition disorders | ||||
Decreased appetite | 3/46 (6.5%) | 3/43 (7%) | ||
Hypocalcaemia | 3/46 (6.5%) | 0/43 (0%) | ||
Hypokalaemia | 3/46 (6.5%) | 0/43 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Back pain | 13/46 (28.3%) | 9/43 (20.9%) | ||
Pain in extremity | 11/46 (23.9%) | 5/43 (11.6%) | ||
Bone pain | 7/46 (15.2%) | 5/43 (11.6%) | ||
Arthralgia | 2/46 (4.3%) | 4/43 (9.3%) | ||
Muscle spasms | 3/46 (6.5%) | 2/43 (4.7%) | ||
Musculoskeletal chest pain | 2/46 (4.3%) | 3/43 (7%) | ||
Musculoskeletal pain | 1/46 (2.2%) | 3/43 (7%) | ||
Osteoarthritis | 1/46 (2.2%) | 3/43 (7%) | ||
Pathological fracture | 3/46 (6.5%) | 1/43 (2.3%) | ||
Pain in jaw | 3/46 (6.5%) | 0/43 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Plasmacytoma | 3/46 (6.5%) | 2/43 (4.7%) | ||
Nervous system disorders | ||||
Polyneuropathy | 3/46 (6.5%) | 6/43 (14%) | ||
Paraesthesia | 5/46 (10.9%) | 3/43 (7%) | ||
Headache | 5/46 (10.9%) | 2/43 (4.7%) | ||
Dizziness | 3/46 (6.5%) | 3/43 (7%) | ||
Dysgeusia | 3/46 (6.5%) | 0/43 (0%) | ||
Psychiatric disorders | ||||
Sleep disorder | 2/46 (4.3%) | 3/43 (7%) | ||
Insomnia | 3/46 (6.5%) | 0/43 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Dyspnoea | 5/46 (10.9%) | 4/43 (9.3%) | ||
Cough | 3/46 (6.5%) | 3/43 (7%) | ||
Dyspnoea exertional | 4/46 (8.7%) | 0/43 (0%) | ||
Epistaxis | 3/46 (6.5%) | 0/43 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Rash | 4/46 (8.7%) | 5/43 (11.6%) | ||
Erythema | 0/46 (0%) | 4/43 (9.3%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title | Medical Communications |
---|---|
Organization | Hoffmann-La Roche |
Phone | 800-821-8590 |
genentech@druginfo.com |
- ML18508
- 2005-003264-38