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Safety and Efficacy of Zoledronic Acid in Patients With Breast Cancer With Metastatic Bone Lesions

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ClinicalTrials.gov Identifier: NCT00375427
Recruitment Status : Completed
First Posted : September 13, 2006
Results First Posted : August 4, 2011
Last Update Posted : April 11, 2012
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer With Bone Metastasis
Intervention Drug: Zoledronic acid
Enrollment 430
Recruitment Details Total enrollment was 430; five participants were screened but not treated.
Pre-assignment Details  
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group. Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Period Title: Overall Study
Started 209 [1] 216
Completed 149 142
Not Completed 60 74
Reason Not Completed
Adverse Event             21             27
Abnormal test procedure result(s)             0             1
Abnormal laboratory value(s)             1             2
Unsatisfactory therapeutic effect             4             4
Patient no longer requires study drug             3             7
Protocol Violation             10             8
Withdrawal by Subject             9             13
Lost to Follow-up             1             1
Administrative reasons             0             1
Death             11             10
[1]
Total enrollment was 430 but five patients were screened but not treated.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks Total
Hide Arm/Group Description Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group. Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions. Total of all reporting groups
Overall Number of Baseline Participants 209 216 425
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 209 participants 216 participants 425 participants
60.4  (11.9) 59.8  (11.8) 60.1  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 209 participants 216 participants 425 participants
Female
209
 100.0%
216
 100.0%
425
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Annual Overall Skeletal Morbidity Rate (SMR)
Hide Description

The SMR was computed by summing all Skeletal Related Event(s) (SREs)which occurred during the observation period and dividing it by the ratio “days of observation period / 365.25”, for each participant. SRE was defined as: pathologic bone fracture, spinal cord compression, surgery to bone both curative and prophylactic, radiation therapy to bone, or hypercalcemia of malignancy.

SMR (years) = 365.25 x SMR(days) where SMR (days) = total number of SREs / total SRE risk period (days). Risk period for SMR was computed as the days from randomization date to the date of last visit.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population will include all randomized patients.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 209 216
Mean (Standard Deviation)
Unit of Measure: Number of Skeletal Events per Year
0.26  (0.81) 0.22  (0.57)
2.Secondary Outcome
Title Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)
Hide Description

Skeletal Related Events (SREs) are defined as a:

  • pathologic bone fracture such as non-vertebral and vertebral compression fractures
  • spinal cord compression identified by positive diagnosis documented by X-ray evidence
  • surgery to bone both curative and prophylactic
  • radiation therapy to bone including palliative, therapeutic or prophylactic
  • hypercalcemia of malignancy, defined as a corrected serum calcium > 12 mg/dl (3.00 mmol/l) or a lower level of hypercalcemia which is symptomatic and which requires active treatment other than rehydration.
Time Frame 12 month
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population will include all randomized patients.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 209 216
Measure Type: Number
Unit of Measure: Percentage of Participants
Patient with any SRE 14.83 15.28
Vertebral pathological fracture 1.44 1.85
Non vertebral pathological fracture 3.35 2.31
Spinal cord compression 0.96 0.46
Radiation to bone 10.53 11.11
Surgery to bone 0.96 0.46
Hypercalcemia of malignancy 0.48 1.85
3.Secondary Outcome
Title Annual Incidence of Any Skeletal Related Events (SREs)
Hide Description

Skeletal Related Events (SREs) are defined as a:

  • pathologic bone fracture such as non-vertebral and vertebral
  • spinal cord compression identified by X-rays evidence
  • surgery to bone both curative and prophylactic
  • radiation therapy to bone including palliative, therapeutic or prophylactic
  • hypercalcemia of malignancy, defined as a corrected serum calcium > 12 mg/dl (3.00 mmol/l) or a lower level of hypercalcemia which is symptomatic and which requires active treatment other than rehydration. Annual incidence for each SRE was computed in the same way as annual overall SMR.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population will include all randomized patients.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 209 216
Mean (Standard Deviation)
Unit of Measure: Number of SRE per Year
Vertebral pathological fracture rate 0.02  (0.19) 0.02  (0.15)
Non-vertebral pathological fracture rate 0.08  (0.58) 0.03  (0.20)
Spinal cord compression rate 0.01  (0.10) 0.00  (0.07)
Radiation to bone rate 0.17  (0.67) 0.14  (0.43)
Surgery to bone rate 0.02  (0.21) 0.00  (0.07)
Hypercalcemia of malignancy rate 0.01  (0.08) 0.02  (0.16)
4.Secondary Outcome
Title Median Time to First Skeletal Related Event(s) (SRE)
Hide Description Median Time to first skeletal related event (SRE) is defined as the time from randomization to the date of first occurrence of any SRE which includes at least one of the following: radiation therapy to bone, pathologic bone fracture, spinal cord compression, surgery to bone, and hypercalcemia of malignancy (HCM). Due to the few numbers of SRE, Kaplan-Meier estimate never reaches a failure probability >=25%; so median time, 25th and 75th percentiles are not determined.For this reason only the estimated percentage of patient SRE free are reported at each time point.
Time Frame 12 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 209 216
Measure Type: Number
Unit of Measure: Day
NA [1]  NA [1] 
[1]
NA=Not evaluable. Due to the low incidence of SRE, K-M estimates never reach a failure probability ≥25%; so median time, 25th and 75th percentiles aren't determined. Time can't be estimated because of insufficient SRE to reach the quartiles
5.Secondary Outcome
Title Percentage of Participants Skeletal Related Event (SRE) Free
Hide Description

Percentage of participants SRE free is defined as the Kaplan-Meier estimate of participants free of any Skeletal Related Events(SRE) at each time point.

Skeletal Related Events (SREs) are:

  • pathologic bone fracture; non-vertebral and vertebral
  • spinal cord compression identified by X-rays
  • surgery to bone both curative and prophylactic
  • radiation therapy to bone (palliative, therapeutic or prophylactic)
  • hypercalcemia of malignancy, defined as a corrected serum calcium > 12 mg/dl (3.00 mmol/l) or a lower level which is symptomatic and requires treatment other than rehydration.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population will include all randomized patients.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 209 216
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
At Month 1
99
(96 to 100)
98
(95 to 99)
At Month 2
98
(94 to 99)
98
(94 to 99)
At Month 3
96
(92 to 98)
97
(93 to 98)
At Month 4
94
(90 to 97)
95
(91 to 97)
At Month 5
94
(89 to 96)
93
(89 to 96)
At Month 6
93
(89 to 96)
92
(87 to 95)
At Month 7
88
(83 to 92)
90
(85 to 93)
At Month 8
86
(80 to 90)
88
(83 to 92)
At Month 9
85
(79 to 90)
85
(79 to 89)
At Month 10
84
(78 to 89)
83
(77 to 88)
At Month 11
83
(77 to 88)
83
(77 to 88)
At Month 12
78
(63 to 87)
82
(75 to 87)
6.Secondary Outcome
Title Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire
Hide Description Bone pain was assessed by means of a pain score obtained using the Brief Pain Inventory (BPI) questionnaire. The BPI can produce three pain scores: worst pain, a composite pain score, and a pain interference score. The composite pain score, which is the average of questions 3, 4, 5 and 6 of the questionnaire was used in this study. Pain was rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The outcome is given as the median score for participants at baseline, and 3, 6, 9 and 12 months of treatment
Time Frame At Baseline, Month 3, Month 6, Month 9 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population will include all randomized patients. All ITT patients with BPI questionnaire filled up at baseline were included.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 186 185
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline (N= 186, 185) 2.0  (1.8) 2.1  (1.9)
Month 3 (N= 156, 163) 2.3  (2.0) 2.2  (1.9)
Month 6 (N= 143, 160) 2.3  (2.2) 1.9  (1.8)
Month 9 (N= 131, 130) 2.3  (2.2) 2.1  (2.0)
Month 12 (N= 135, 124) 2.4  (2.3) 2.1  (2.0)
7.Secondary Outcome
Title Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value
Hide Description Pain intensity at rest and on movement is rated by the patient by means of a validated 6-point Verbal Rating Scale (VRS) and refers to the pain which occurred during the last week before the assessment. Median score value is the median of all the observed scores (none=0, very mild=1, mild=2, moderate=3, severe=5 and very severe=6) at each time point.
Time Frame At Baseline, Month 3, Month 6, Month 9 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population will include all randomized patients.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 209 216
Median (Full Range)
Unit of Measure: score on a scale
At Rest: Baseline
1
(1.00 to 5.00)
1
(1.00 to 6.00)
At Rest: Month 3
2
(1.00 to 6.00)
2
(1.00 to 5.00)
At Rest: Month 6
2
(1.00 to 5.00)
1
(1.00 to 6.00)
At Rest: Month 9
1
(1.00 to 5.00)
1
(1.00 to 5.00)
At Rest: Month 12
2
(1.00 to 6.00)
1
(1.00 to 6.00)
At Movement : Baseline
2
(1.00 to 5.00)
2
(1.00 to 6.00)
At Movement : Month 3
2
(1.00 to 6.00)
2
(1.00 to 6.00)
At Movement : Month 6
2
(1.00 to 6.00)
2
(1.00 to 6.00)
At Movement : Month 9
2
(1.00 to 6.00)
2
(1.00 to 6.00)
At Movement : Month 12
2.5
(1.00 to 6.00)
2
(1.00 to 6.00)
8.Secondary Outcome
Title Use Of Analgesic Medications According to the Analgesic Score Scale
Hide Description

The analgesic score used for this study is modified from the Radiation Therapy Oncology Group (RTOG) analgesic score scale. The scale represents type of medication administered from 0 to 4 where:

0 = None

  1. = Minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.)
  2. = Tranquilisers, antidepressants, muscle relaxants, and steroids
  3. = Mild narcotics (oxycodone, meperidine, codeine, etc.)
  4. = Strong narcotics (morphine, hydromorphone, etc.) The outcome is given a the median score for the participants at Baseline and 3, 6, 9 and 12 months of treatment
Time Frame At Baseline, Month 3, Month 6, Month 9 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population will include all randomized patients.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 209 216
Median (Full Range)
Unit of Measure: score on a scale
Baseline
0
(0 to 4)
0
(0 to 4)
Month 3
0
(0 to 4)
0
(0 to 4)
Month 6
0
(0 to 4)
0
(0 to 4)
Month 9
0
(0 to 4)
0
(0 to 4)
Month 12
0
(0 to 4)
0
(0 to 4)
9.Secondary Outcome
Title Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score
Hide Description ECOG Performance Score has 4 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. Outcome is given as median score for participants at Baseline and 3, 6 , 9 and 12 months of treatment
Time Frame At Baseline, Month 3, Month 6, Month 9 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population will include all randomized patients.
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description:
Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group.
Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions.
Overall Number of Participants Analyzed 209 216
Median (Full Range)
Unit of Measure: score on a scale
Baseline
0
(0 to 2)
0
(0 to 2)
Month 3
0
(0 to 3)
0
(0 to 3)
Month 6
0
(0 to 2)
0
(0 to 2)
Month 9
0
(0 to 2)
0
(0 to 2)
Month 12
0
(0 to 4)
0
(0 to 4)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Hide Arm/Group Description Zoledronic acid given as a 15-minute (at least) i.v. infusion every three months. The dose of study drug was the same as administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized participants received a maximum of 4 infusions in this group. Zoledronic acid given as a 15-minute (at least) i.v. infusion every 4 weeks. The dose of study drug was the as same administered before study entry; that is, 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Participants randomized to this group received up to 12 infusions
All-Cause Mortality
Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   21/209 (10.05%)   29/216 (13.43%) 
Blood and lymphatic system disorders     
Anaemia  1  0/209 (0.00%)  2/216 (0.93%) 
Febrile neutropenia  1  0/209 (0.00%)  2/216 (0.93%) 
Thrombocytopenia  1  0/209 (0.00%)  2/216 (0.93%) 
Cardiac disorders     
Acute myocardial infarction  1  0/209 (0.00%)  1/216 (0.46%) 
Cardiac failure  1  0/209 (0.00%)  1/216 (0.46%) 
Eye disorders     
Diplopia  1  0/209 (0.00%)  1/216 (0.46%) 
Gastrointestinal disorders     
Gastric haemorrhage  1  0/209 (0.00%)  1/216 (0.46%) 
Nausea  1  0/209 (0.00%)  1/216 (0.46%) 
Oral pain  1  0/209 (0.00%)  2/216 (0.93%) 
Vomiting  1  1/209 (0.48%)  2/216 (0.93%) 
General disorders     
Mucosal inflammation  1  0/209 (0.00%)  1/216 (0.46%) 
Pain  1  1/209 (0.48%)  0/216 (0.00%) 
Hepatobiliary disorders     
Jaundice  1  0/209 (0.00%)  1/216 (0.46%) 
Infections and infestations     
Acute sinusitis  1  1/209 (0.48%)  0/216 (0.00%) 
Pneumonia  1  0/209 (0.00%)  1/216 (0.46%) 
Sepsis  1  0/209 (0.00%)  1/216 (0.46%) 
Skin infection  1  0/209 (0.00%)  1/216 (0.46%) 
Injury, poisoning and procedural complications     
Femur fracture  1  2/209 (0.96%)  1/216 (0.46%) 
Humerus fracture  1  0/209 (0.00%)  1/216 (0.46%) 
Metabolism and nutrition disorders     
Cachexia  1  1/209 (0.48%)  1/216 (0.46%) 
Hypercalcaemia  1  0/209 (0.00%)  1/216 (0.46%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  1/209 (0.48%)  2/216 (0.93%) 
Jaw disorder  1  0/209 (0.00%)  1/216 (0.46%) 
Musculoskeletal chest pain  1  1/209 (0.48%)  0/216 (0.00%) 
Osteitis  1  0/209 (0.00%)  1/216 (0.46%) 
Osteonecrosis  1  4/209 (1.91%)  3/216 (1.39%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression  1  2/209 (0.96%)  1/216 (0.46%) 
Metastases to central nervous system  1  1/209 (0.48%)  0/216 (0.00%) 
Nervous system disorders     
Cranial nerve paralysis  1  0/209 (0.00%)  1/216 (0.46%) 
Epilepsy  1  1/209 (0.48%)  0/216 (0.00%) 
Ischaemic cerebral infarction  1  0/209 (0.00%)  1/216 (0.46%) 
Paraparesis  1  0/209 (0.00%)  1/216 (0.46%) 
Psychiatric disorders     
Depression  1  1/209 (0.48%)  0/216 (0.00%) 
Sopor  1  0/209 (0.00%)  1/216 (0.46%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  2/209 (0.96%)  2/216 (0.93%) 
Dyspnoea exertional  1  0/209 (0.00%)  1/216 (0.46%) 
Haemoptysis  1  0/209 (0.00%)  1/216 (0.46%) 
Pleural effusion  1  0/209 (0.00%)  1/216 (0.46%) 
Pulmonary embolism  1  1/209 (0.48%)  0/216 (0.00%) 
Surgical and medical procedures     
Breast operation  1  1/209 (0.48%)  0/216 (0.00%) 
Laparoscopic surgery  1  0/209 (0.00%)  1/216 (0.46%) 
Vascular disorders     
Deep vein thrombosis  1  1/209 (0.48%)  1/216 (0.46%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Zoledronic Acid Every 3 Months Zoledronic Acid Every 4 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   133/209 (63.64%)   161/216 (74.54%) 
Blood and lymphatic system disorders     
Anaemia  1  13/209 (6.22%)  21/216 (9.72%) 
Neutropenia  1  11/209 (5.26%)  18/216 (8.33%) 
Ear and labyrinth disorders     
Vertigo  1  2/209 (0.96%)  11/216 (5.09%) 
Gastrointestinal disorders     
Abdominal pain  1  12/209 (5.74%)  15/216 (6.94%) 
Abdominal pain upper  1  16/209 (7.66%)  20/216 (9.26%) 
Constipation  1  12/209 (5.74%)  15/216 (6.94%) 
Diarrhoea  1  12/209 (5.74%)  17/216 (7.87%) 
Nausea  1  24/209 (11.48%)  32/216 (14.81%) 
Vomiting  1  13/209 (6.22%)  21/216 (9.72%) 
General disorders     
Asthenia  1  18/209 (8.61%)  33/216 (15.28%) 
Fatigue  1  10/209 (4.78%)  12/216 (5.56%) 
Pain  1  10/209 (4.78%)  15/216 (6.94%) 
Pyrexia  1  22/209 (10.53%)  28/216 (12.96%) 
Investigations     
Gamma-glutamyltransferase increased  1  8/209 (3.83%)  12/216 (5.56%) 
Metabolism and nutrition disorders     
Anorexia  1  5/209 (2.39%)  12/216 (5.56%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/209 (4.31%)  13/216 (6.02%) 
Back pain  1  7/209 (3.35%)  13/216 (6.02%) 
Bone pain  1  56/209 (26.79%)  64/216 (29.63%) 
Pain in extremity  1  8/209 (3.83%)  12/216 (5.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression  1  67/209 (32.06%)  68/216 (31.48%) 
Nervous system disorders     
Headache  1  14/209 (6.70%)  15/216 (6.94%) 
Paraesthesia  1  11/209 (5.26%)  8/216 (3.70%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  14/209 (6.70%)  12/216 (5.56%) 
Dyspnoea  1  9/209 (4.31%)  13/216 (6.02%) 
Skin and subcutaneous tissue disorders     
Rash  1  3/209 (1.44%)  12/216 (5.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00375427     History of Changes
Other Study ID Numbers: CZOL446EIT14
First Submitted: September 12, 2006
First Posted: September 13, 2006
Results First Submitted: February 28, 2011
Results First Posted: August 4, 2011
Last Update Posted: April 11, 2012