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Trial record 114 of 199 for:    osteonecrosis

Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Multiple Myeloma (COMPARE)

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ClinicalTrials.gov Identifier: NCT02739594
Recruitment Status : Terminated (Slow recruitment)
First Posted : April 15, 2016
Results First Posted : July 22, 2016
Last Update Posted : July 22, 2016
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Ibandronate
Drug: Zoledronate
Enrollment 89
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ibandronate Zoledronate
Hide 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 [1] 15 [1]
Not Completed 25 28
Reason Not Completed
Undesired Event             3             4
Violation of Eligibility Criteria             1             2
Protocol Violation             5             6
Death             4             2
Renal Insufficiency             4             6
Administrative Reasons             1             3
Withdrawal by Subject             1             1
Lost to Follow-up             0             1
Elevated Serum Creatinine             0             1
Not Specified             6             2
[1]
Includes all participants who reached the protocol-defined end of study (either Week 44 or 96).
Arm/Group Title Ibandronate Zoledronate Total
Hide 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 Number of Baseline Participants 41 40 81
Hide Baseline Analysis Population Description
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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 40 participants 81 participants
65.3  (9.4) 69.1  (9.1) 67.2  (9.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 40 participants 81 participants
Female
15
  36.6%
14
  35.0%
29
  35.8%
Male
26
  63.4%
26
  65.0%
52
  64.2%
1.Primary Outcome
Title Percentage of Participants With Deterioration in Renal Function According to Reduction in Creatinine Clearance (CrCl) From Baseline to Week 44
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population.
Arm/Group Title Ibandronate Zoledronate
Hide 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.
Overall Number of Participants Analyzed 41 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
9.8
(2.7 to 23.1)
12.5
(4.2 to 26.8)
2.Primary Outcome
Title Percentage of Participants With Deterioration in Renal Function According to Reduction in CrCl From Baseline to Week 92
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ibandronate Zoledronate
Hide 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.
Overall Number of Participants Analyzed 41 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.6
(5.6 to 29.2)
12.5
(4.2 to 26.8)
3.Secondary Outcome
Title Percentage of Participants With Skeletal-Related Events (SREs)
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ibandronate Zoledronate
Hide 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.
Overall Number of Participants Analyzed 41 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.0
(10.6 to 37.6)
30.0
(16.6 to 46.5)
4.Secondary Outcome
Title Time to First SRE
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ibandronate Zoledronate
Hide 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.
Overall Number of Participants Analyzed 41 40
Median (Full Range)
Unit of Measure: days
393.0
(12 to 727)
244.5
(21 to 693)
5.Secondary Outcome
Title Number of SREs for Each Participant
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ibandronate Zoledronate
Hide 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.
Overall Number of Participants Analyzed 41 40
Mean (Standard Deviation)
Unit of Measure: SREs
0.3  (0.6) 0.5  (1.1)
6.Secondary Outcome
Title Percentage of Participants With Osteonecrosis of Jaw
Time Frame From Baseline to end of study (up to Week 96)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ibandronate Zoledronate
Hide 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.
Overall Number of Participants Analyzed 41 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 8.6)
0.0
(0.0 to 8.8)
7.Secondary Outcome
Title Number of Events of Osteonecrosis of Jaw for Each Participant
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ibandronate Zoledronate
Hide 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.
Overall Number of Participants Analyzed 41 40
Mean (Standard Deviation)
Unit of Measure: events of osteonecrosis of jaw
0.0  (0.0) 0.0  (0.0)
8.Secondary Outcome
Title Percentage of Participants With Zoledronate Dose Reduction
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only the Zoledronate arm was included.
Arm/Group Title Zoledronate
Hide 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.
Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
30.0
(16.6 to 46.5)
9.Secondary Outcome
Title Number of Zoledronate Dose Reductions for Each Participant
Hide 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)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population; only the Zoledronate arm was included.
Arm/Group Title Zoledronate
Hide 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.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: dose reductions
0.8  (1.4)
10.Secondary Outcome
Title Percent Change From Baseline in N-Acetyl-Beta-D-Glucosaminidase (B-NAG)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 38 37
Median (Full Range)
Unit of Measure: percent change
Week 44
-15.7
(-86 to 355)
10.6
(-94 to 156)
Week 92
-17.2
(-78 to 355)
9.3
(-94 to 125)
11.Secondary Outcome
Title Percent Change From Baseline in Alpha (A) 1-Microglobulin
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 38 37
Median (Full Range)
Unit of Measure: percent change
Week 44
0.0
(-85 to 706)
0.0
(-86 to 429)
Week 92
0.0
(-85 to 706)
0.0
(-86 to 591)
12.Secondary Outcome
Title Percent Change From Baseline in Gamma-Glutamyltransferase (GGT)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 38 37
Median (Full Range)
Unit of Measure: percent change
Week 44
-6.0
(-57 to 393)
3.8
(-66 to 50)
Week 92
-2.5
(-57 to 393)
3.8
(-66 to 61)
13.Secondary Outcome
Title Percentage of Participants With Elevation of Serum Creatinine (SCr) From Baseline
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Ibandronate Zoledronate
Hide 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.
Overall Number of Participants Analyzed 41 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 44
2.4
(0.1 to 12.9)
2.5
(0.1 to 13.2)
Week 92
7.3
(1.5 to 19.9)
2.5
(0.1 to 13.2)
14.Secondary Outcome
Title Percent Change From Baseline in CrCl
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 41 40
Mean (Standard Deviation)
Unit of Measure: percent change
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)
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
Hide 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 (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ibandronate Zoledronate
Affected / at Risk (%) Affected / at Risk (%)
Total   27/46 (58.70%)   18/43 (41.86%) 
Blood and lymphatic system disorders     
Anaemia * 1  0/46 (0.00%)  1/43 (2.33%) 
Febrile neutropenia * 1  1/46 (2.17%)  0/43 (0.00%) 
Normochromic normocytic anaemia * 1  0/46 (0.00%)  1/43 (2.33%) 
Pancytopenia * 1  1/46 (2.17%)  0/43 (0.00%) 
Thrombocytopenia * 1  1/46 (2.17%)  0/43 (0.00%) 
Cardiac disorders     
Arrhythmia * 1  1/46 (2.17%)  0/43 (0.00%) 
Atrial fibrillation * 1  1/46 (2.17%)  0/43 (0.00%) 
Cardiac failure * 1  1/46 (2.17%)  1/43 (2.33%) 
Myocardial infarction * 1  0/46 (0.00%)  1/43 (2.33%) 
Gastrointestinal disorders     
Diarrhoea * 1  2/46 (4.35%)  0/43 (0.00%) 
Diverticulum * 1  1/46 (2.17%)  0/43 (0.00%) 
Enteritis * 1  0/46 (0.00%)  1/43 (2.33%) 
Gastrointestinal haemorrhage * 1  1/46 (2.17%)  0/43 (0.00%) 
Vomiting * 1  1/46 (2.17%)  0/43 (0.00%) 
General disorders     
Asthenia * 1  1/46 (2.17%)  0/43 (0.00%) 
General physical health deterioration * 1  2/46 (4.35%)  0/43 (0.00%) 
Pyrexia * 1  2/46 (4.35%)  0/43 (0.00%) 
Infections and infestations     
Abscess oral * 1  0/46 (0.00%)  1/43 (2.33%) 
Bronchitis * 1  1/46 (2.17%)  0/43 (0.00%) 
Bronchopneumonia * 1  1/46 (2.17%)  0/43 (0.00%) 
Gastroenteritis * 1  1/46 (2.17%)  0/43 (0.00%) 
Herpes zoster * 1  1/46 (2.17%)  0/43 (0.00%) 
Implant site infection * 1  1/46 (2.17%)  1/43 (2.33%) 
Infection * 1  3/46 (6.52%)  0/43 (0.00%) 
Pneumocystis jiroveci pneumonia * 1  0/46 (0.00%)  1/43 (2.33%) 
Pneumonia * 1  4/46 (8.70%)  1/43 (2.33%) 
Septic shock * 1  2/46 (4.35%)  1/43 (2.33%) 
Urosepsis * 1  1/46 (2.17%)  0/43 (0.00%) 
Injury, poisoning and procedural complications     
Fracture * 1  0/46 (0.00%)  1/43 (2.33%) 
Humerus fracture * 1  0/46 (0.00%)  1/43 (2.33%) 
Lumbar vertebral fracture * 1  1/46 (2.17%)  0/43 (0.00%) 
Post procedural swelling * 1  1/46 (2.17%)  0/43 (0.00%) 
Investigations     
Blood creatinine increased * 1  3/46 (6.52%)  1/43 (2.33%) 
Creatinine renal clearance decreased * 1  2/46 (4.35%)  4/43 (9.30%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/46 (2.17%)  0/43 (0.00%) 
Diabetes mellitus * 1  1/46 (2.17%)  0/43 (0.00%) 
Hyperglycaemia * 1  1/46 (2.17%)  1/43 (2.33%) 
Hypokalaemia * 1  1/46 (2.17%)  0/43 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/46 (2.17%)  0/43 (0.00%) 
Bone pain * 1  2/46 (4.35%)  0/43 (0.00%) 
Intervertebral disc compression * 1  0/46 (0.00%)  1/43 (2.33%) 
Musculoskeletal chest pain * 1  1/46 (2.17%)  0/43 (0.00%) 
Pathological fracture * 1  1/46 (2.17%)  0/43 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Multiple myeloma * 1  4/46 (8.70%)  0/43 (0.00%) 
Neoplasm progression * 1  1/46 (2.17%)  0/43 (0.00%) 
Plasmacytoma * 1  1/46 (2.17%)  0/43 (0.00%) 
Nervous system disorders     
Dizziness * 1  1/46 (2.17%)  0/43 (0.00%) 
Paraplegia * 1  0/46 (0.00%)  1/43 (2.33%) 
Syncope * 1  1/46 (2.17%)  1/43 (2.33%) 
Renal and urinary disorders     
Nephropathy toxic * 1  0/46 (0.00%)  1/43 (2.33%) 
Renal failure * 1  1/46 (2.17%)  0/43 (0.00%) 
Renal failure acute * 1  1/46 (2.17%)  0/43 (0.00%) 
Renal failure chronic * 1  1/46 (2.17%)  0/43 (0.00%) 
Renal impairment * 1  0/46 (0.00%)  1/43 (2.33%) 
Urinary retention * 1  0/46 (0.00%)  1/43 (2.33%) 
Respiratory, thoracic and mediastinal disorders     
Bronchial haemorrhage * 1  1/46 (2.17%)  0/43 (0.00%) 
Dyspnoea * 1  0/46 (0.00%)  1/43 (2.33%) 
Pleural effusion * 1  1/46 (2.17%)  0/43 (0.00%) 
Pulmonary embolism * 1  1/46 (2.17%)  0/43 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin haemorrhage * 1  0/46 (0.00%)  1/43 (2.33%) 
Vascular disorders     
Circulatory collapse * 1  1/46 (2.17%)  0/43 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ibandronate Zoledronate
Affected / at Risk (%) Affected / at Risk (%)
Total   43/46 (93.48%)   34/43 (79.07%) 
Blood and lymphatic system disorders     
Anaemia * 1  11/46 (23.91%)  11/43 (25.58%) 
Leukopenia * 1  10/46 (21.74%)  7/43 (16.28%) 
Thrombocytopenia * 1  6/46 (13.04%)  3/43 (6.98%) 
Ear and labyrinth disorders     
Vertigo * 1  3/46 (6.52%)  2/43 (4.65%) 
Gastrointestinal disorders     
Diarrhoea * 1  10/46 (21.74%)  8/43 (18.60%) 
Nausea * 1  6/46 (13.04%)  9/43 (20.93%) 
Constipation * 1  4/46 (8.70%)  4/43 (9.30%) 
Vomiting * 1  4/46 (8.70%)  1/43 (2.33%) 
Dry mouth * 1  1/46 (2.17%)  3/43 (6.98%) 
General disorders     
Oedema peripheral * 1  7/46 (15.22%)  10/43 (23.26%) 
Fatigue * 1  7/46 (15.22%)  7/43 (16.28%) 
Pyrexia * 1  6/46 (13.04%)  7/43 (16.28%) 
Pain * 1  4/46 (8.70%)  4/43 (9.30%) 
Chills * 1  1/46 (2.17%)  3/43 (6.98%) 
Chest pain * 1  0/46 (0.00%)  3/43 (6.98%) 
General physical health deterioration * 1  3/46 (6.52%)  0/43 (0.00%) 
Infections and infestations     
Nasopharyngitis * 1  19/46 (41.30%)  10/43 (23.26%) 
Bronchitis * 1  8/46 (17.39%)  3/43 (6.98%) 
Candidiasis * 1  4/46 (8.70%)  5/43 (11.63%) 
Herpes zoster * 1  2/46 (4.35%)  7/43 (16.28%) 
Influenza * 1  4/46 (8.70%)  2/43 (4.65%) 
Pneumonia * 1  3/46 (6.52%)  0/43 (0.00%) 
Urinary tract infection * 1  3/46 (6.52%)  0/43 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  3/46 (6.52%)  3/43 (6.98%) 
Hypocalcaemia * 1  3/46 (6.52%)  0/43 (0.00%) 
Hypokalaemia * 1  3/46 (6.52%)  0/43 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  13/46 (28.26%)  9/43 (20.93%) 
Pain in extremity * 1  11/46 (23.91%)  5/43 (11.63%) 
Bone pain * 1  7/46 (15.22%)  5/43 (11.63%) 
Arthralgia * 1  2/46 (4.35%)  4/43 (9.30%) 
Muscle spasms * 1  3/46 (6.52%)  2/43 (4.65%) 
Musculoskeletal chest pain * 1  2/46 (4.35%)  3/43 (6.98%) 
Musculoskeletal pain * 1  1/46 (2.17%)  3/43 (6.98%) 
Osteoarthritis * 1  1/46 (2.17%)  3/43 (6.98%) 
Pathological fracture * 1  3/46 (6.52%)  1/43 (2.33%) 
Pain in jaw * 1  3/46 (6.52%)  0/43 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Plasmacytoma * 1  3/46 (6.52%)  2/43 (4.65%) 
Nervous system disorders     
Polyneuropathy * 1  3/46 (6.52%)  6/43 (13.95%) 
Paraesthesia * 1  5/46 (10.87%)  3/43 (6.98%) 
Headache * 1  5/46 (10.87%)  2/43 (4.65%) 
Dizziness * 1  3/46 (6.52%)  3/43 (6.98%) 
Dysgeusia * 1  3/46 (6.52%)  0/43 (0.00%) 
Psychiatric disorders     
Sleep disorder * 1  2/46 (4.35%)  3/43 (6.98%) 
Insomnia * 1  3/46 (6.52%)  0/43 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  5/46 (10.87%)  4/43 (9.30%) 
Cough * 1  3/46 (6.52%)  3/43 (6.98%) 
Dyspnoea exertional * 1  4/46 (8.70%)  0/43 (0.00%) 
Epistaxis * 1  3/46 (6.52%)  0/43 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash * 1  4/46 (8.70%)  5/43 (11.63%) 
Erythema * 1  0/46 (0.00%)  4/43 (9.30%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02739594     History of Changes
Other Study ID Numbers: ML18508
2005-003264-38 ( EudraCT Number )
First Submitted: April 12, 2016
First Posted: April 15, 2016
Results First Submitted: June 9, 2016
Results First Posted: July 22, 2016
Last Update Posted: July 22, 2016