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Continued Efficacy and Safety of Zoledronic Acid (q 4 Wks vs. q 12 Wks) in the 2nd Year of Treatment in Patients With Bone Metastases From Breast Cancer

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ClinicalTrials.gov Identifier: NCT00320710
Recruitment Status : Completed
First Posted : May 3, 2006
Results First Posted : August 4, 2014
Last Update Posted : August 22, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Breast Cancer
Interventions Drug: Zoledronic acid
Drug: Placebo
Enrollment 416
Recruitment Details The initial study design contained 3 arms: zoledronic acid q4 weeks, zoledronic acid q12 weeks and placebo q4 weeks. Due to a study amendment, the placebo arm was discontinued and participants in this treatment group were switched to the zoledronic acid q4 week group. These participants were not included in the efficacy analysis.
Pre-assignment Details  
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
Hide Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were later switched to the zoledronic acid q 4 weeks according to a study amendment.
Period Title: Overall Study
Started 200 203 13
Treated (Safety Set) 198 202 13
Completed 106 127 8
Not Completed 94 76 5
Reason Not Completed
Disease progression             24             19             2
Death             10             7             1
Administrative problems             1             2             0
Withdrawal by Subject             20             26             1
Protocol Violation             6             5             0
Abnormal test procedure result(s)             2             0             0
Abnormal laboratory value(s)             12             3             0
Adverse Event             18             14             1
Lost to Follow-up             1             0             0
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid Total
Hide Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were later switched to the zoledronic acid q 4 weeks according to a study amendment. Total of all reporting groups
Overall Number of Baseline Participants 200 203 13 416
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 200 participants 203 participants 13 participants 416 participants
59.2  (11.10) 58.6  (11.15) 60.8  (12.19) 58.9  (11.14)
Sex/Gender, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 200 participants 203 participants 13 participants 416 participants
200 203 13 416
[1]
Measure Description: All participants were female.
1.Primary Outcome
Title Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE)
Hide Description An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
Hide Arm/Group Description:
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
Overall Number of Participants Analyzed 200 203
Measure Type: Number
Unit of Measure: Percentage of participants
22 23.2
2.Secondary Outcome
Title Time to First SRE
Hide Description An SRE was defined as a pathologic bone fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone, or surgery to bone. The time to first individual SRE was defined as the date of randomization to the date of first occurrence of any SRE.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
Hide Arm/Group Description:
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
Overall Number of Participants Analyzed 200 203
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
The median was not estimable because there were too few events to calculate the median.
3.Secondary Outcome
Title Time to First Individual Type of SRE
Hide Description Types of SREs analyzed were pathologic fractures (vertebral and non-vertebral), spinal cord compression, radiation to bone and surgery to bone. The time to first indvidual SRE was defined as the date of randomization to the date of the first occurrence of any individual SRE.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
Hide Arm/Group Description:
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
Overall Number of Participants Analyzed 200 203
Median (95% Confidence Interval)
Unit of Measure: Weeks
Vertebral pathologic fractures
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Non-vertebral pathologic fractures
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Spinal cord compression
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Radiation to bone
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Surgery to bone
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
The median was not estimable because too few events occurred to calculate the median.
4.Secondary Outcome
Title Change From Baseline in Mean Composite Brief Pain Inventory (BPI) Score
Hide Description Participants completed a BPI short form which is a 9 item self-administered questionnaire used to evaluate the severity of a participant's pain and the impact of this pain on the participant's daily functioning. The participant rates his or her worst, least, average, and current pain intensity, lists current treatments and perceived effectiveness, and rates the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10 point scale. The BPI composite score, which was calculated as the average of items 3, 4, 5 and 6 (worst pain, least pain, average pain and pain right now), ranged from 0 (best possible outcome, no pain) to 10 (worst possible outcome, pain as bad as you can imagine). A positive change from baseline indicates worsening.
Time Frame baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups and had both baseline and week 52 values.
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
Hide Arm/Group Description:
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
Overall Number of Participants Analyzed 89 100
Mean (Standard Deviation)
Unit of Measure: scores on a scale
0.24  (1.976) 0.31  (2.099)
5.Secondary Outcome
Title Change From Baseline in Mean Analgesic Score
Hide Description The analgesic score indicates the types of pain medication used. The scores range as follows: 0 = none medication; 1 = minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.); 2 = Tranquilizers, antidepressants, muscle relaxants, and steroids; 3 = Mild narcotics (oxycodone, meperidine, codeine, etc.); and 4 = Strong narcotics (morphine, hydromorphone, etc.). A positive change from baseline indicates worsening.
Time Frame baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups and had both baseline and week 52 values.
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
Hide Arm/Group Description:
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
Overall Number of Participants Analyzed 94 104
Mean (Standard Deviation)
Unit of Measure: score
0.5  (1.28) 0.5  (1.13)
6.Secondary Outcome
Title Change From Baseline in Urinary N-telopeptide / Creatinine Ratio
Hide Description Urine samples were collected to obtain n-telopeptide and creatinine values.
Time Frame baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups and had both baseline and week 48 values.
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
Hide Arm/Group Description:
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
Overall Number of Participants Analyzed 106 119
Mean (Standard Deviation)
Unit of Measure: ratio
10.612  (40.4073) 14.697  (57.7315)
7.Secondary Outcome
Title Change From Baseline in Serum Bone Specific Alkaline Phosphatase
Hide Description Serum samples were collected to obtain bone specific alkaline phosphatase values.
Time Frame baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups and had both baseline and week 48 values.
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
Hide Arm/Group Description:
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
Overall Number of Participants Analyzed 93 105
Mean (Standard Deviation)
Unit of Measure: mcg/L
0.797  (27.8800) 4.514  (12.4509)
8.Secondary Outcome
Title Skeletal Morbidity Rate
Hide Description An SMR for a patient was defined as the "number of occurrences" of any (or a particular) SRE allowing for only 1 event in any 3-week interval, divided by the "time at risk" in years. The "number of occurrences" and the "time at risk" were counts of SRE and the time from the randomization date. Counting began from randomization in the way that every counted event was followed by a 20-day period during which no SRE was counted, nor was the time counted as "at risk". For example, if a patient had 1 SRE during the study, the "time at risk" was calculated as the total number of days in the study minus the 20-day follow-up period for that SRE. If a patient had no SRE events, the entire study period was counted as "time at risk". This SMR calculation method had the advantage of avoiding multiple counts of possibly interdependent SREs (e.g. having 1 fracture increases the probability of having a subsequent SRE).
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This population included all participants who were in the zoledronic acid q 4 weeks and zoledronic acid q 12 weeks treatment groups.
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks
Hide Arm/Group Description:
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind.
Overall Number of Participants Analyzed 200 203
Mean (Standard Deviation)
Unit of Measure: Number of events per year
0.46  (1.063) 0.50  (1.500)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
Hide Arm/Group Description Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were later switched to the zoledronic acid q 4 weeks according to a study amendment.
All-Cause Mortality
Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   50/198 (25.25%)   51/202 (25.25%)   3/13 (23.08%) 
Blood and lymphatic system disorders       
Anaemia † 1  1/198 (0.51%)  3/202 (1.49%)  0/13 (0.00%) 
Febrile neutropenia † 1  1/198 (0.51%)  2/202 (0.99%)  0/13 (0.00%) 
Leukocytosis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Leukopenia † 1  2/198 (1.01%)  0/202 (0.00%)  0/13 (0.00%) 
Neutropenia † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Pancytopenia † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Cardiac disorders       
Atrial fibrillation † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Cardiac failure congestive † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Palpitations † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Pericardial effusion † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Supraventricular tachycardia † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Tachycardia † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Congenital, familial and genetic disorders       
Arteriovenous malformation † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Endocrine disorders       
Hypercalcaemia of malignancy † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Eye disorders       
Eye swelling † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Gastrointestinal disorders       
Abdominal pain † 1  2/198 (1.01%)  5/202 (2.48%)  0/13 (0.00%) 
Ascites † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Diarrhoea † 1  3/198 (1.52%)  3/202 (1.49%)  0/13 (0.00%) 
Dysphagia † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Gastrointestinal haemorrhage † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Haematemesis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Megacolon † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Mesenteric vein thrombosis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Nausea † 1  2/198 (1.01%)  2/202 (0.99%)  0/13 (0.00%) 
Oesophageal stenosis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Oesophagitis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Oral disorder † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Varices oesophageal † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Vomiting † 1  3/198 (1.52%)  2/202 (0.99%)  0/13 (0.00%) 
General disorders       
Asthenia † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Disease progression † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Drug withdrawal syndrome † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Fibrosis † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
General physical health deterioration † 1  2/198 (1.01%)  2/202 (0.99%)  0/13 (0.00%) 
Generalised oedema † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Mucosal inflammation † 1  0/198 (0.00%)  1/202 (0.50%)  1/13 (7.69%) 
Oedema peripheral † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Pain † 1  2/198 (1.01%)  0/202 (0.00%)  0/13 (0.00%) 
Perforated ulcer † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Pyrexia † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Hepatobiliary disorders       
Biliary dilatation † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Cholangitis † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Hepatic failure † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Infections and infestations       
Bronchitis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Cellulitis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Clostridium difficile colitis † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Escherichia sepsis † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Gastroenteritis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Pneumonia † 1  4/198 (2.02%)  1/202 (0.50%)  0/13 (0.00%) 
Sepsis † 1  2/198 (1.01%)  0/202 (0.00%)  0/13 (0.00%) 
Septic shock † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Urinary tract infection † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Injury, poisoning and procedural complications       
Clavicle fracture † 1  2/198 (1.01%)  0/202 (0.00%)  0/13 (0.00%) 
Comminuted fracture † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Femur fracture † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Procedural pain † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Spinal compression fracture † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Subdural haematoma † 1  0/198 (0.00%)  3/202 (1.49%)  0/13 (0.00%) 
Investigations       
Hepatic enzyme increased † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Troponin increased † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Metabolism and nutrition disorders       
Dehydration † 1  4/198 (2.02%)  4/202 (1.98%)  0/13 (0.00%) 
Failure to thrive † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Hypercalcaemia † 1  1/198 (0.51%)  2/202 (0.99%)  0/13 (0.00%) 
Hypocalcaemia † 1  1/198 (0.51%)  0/202 (0.00%)  1/13 (7.69%) 
Hypokalaemia † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Bone pain † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Muscular weakness † 1  2/198 (1.01%)  1/202 (0.50%)  0/13 (0.00%) 
Musculoskeletal chest pain † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Musculoskeletal pain † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Musculoskeletal stiffness † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Osteoarthritis † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Osteonecrosis of jaw † 1  2/198 (1.01%)  2/202 (0.99%)  0/13 (0.00%) 
Pain in extremity † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Pathological fracture † 1  1/198 (0.51%)  0/202 (0.00%)  1/13 (7.69%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Breast cancer metastatic † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Metastases to bone † 1  3/198 (1.52%)  0/202 (0.00%)  0/13 (0.00%) 
Metastases to central nervous system † 1  0/198 (0.00%)  2/202 (0.99%)  0/13 (0.00%) 
Metastases to liver † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Metastases to lung † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Metastases to meninges † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Non-small cell lung cancer † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Nervous system disorders       
Brain mass † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Cerebral haemorrhage † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Coma † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Convulsion † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Depressed level of consciousness † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Encephalopathy † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Hemiparesis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Hepatic encephalopathy † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Hydrocephalus † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Migraine † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Somnolence † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Spinal cord compression † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Vasogenic cerebral oedema † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Psychiatric disorders       
Acute psychosis † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Confusional state † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Delirium † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Mental status changes † 1  0/198 (0.00%)  2/202 (0.99%)  0/13 (0.00%) 
Renal and urinary disorders       
Haematuria † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Hydronephrosis † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Renal failure † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Renal failure acute † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Urinary tract obstruction † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Reproductive system and breast disorders       
Pelvic pain † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Dyspnoea † 1  3/198 (1.52%)  5/202 (2.48%)  0/13 (0.00%) 
Haemoptysis † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Hypoxia † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Pleural effusion † 1  1/198 (0.51%)  4/202 (1.98%)  1/13 (7.69%) 
Pulmonary embolism † 1  2/198 (1.01%)  1/202 (0.50%)  0/13 (0.00%) 
Respiratory distress † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Respiratory failure † 1  1/198 (0.51%)  1/202 (0.50%)  0/13 (0.00%) 
Tachypnoea † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Skin and subcutaneous tissue disorders       
Decubitus ulcer † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Swelling face † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
Vascular disorders       
Deep vein thrombosis † 1  1/198 (0.51%)  2/202 (0.99%)  0/13 (0.00%) 
Hypertension † 1  0/198 (0.00%)  1/202 (0.50%)  0/13 (0.00%) 
Hypotension † 1  2/198 (1.01%)  1/202 (0.50%)  0/13 (0.00%) 
Orthostatic hypotension † 1  1/198 (0.51%)  0/202 (0.00%)  0/13 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Zoledronic Acid Every (q) 4 Weeks Zoledronic Acid q 12 Weeks Placebo / Zoledronic Acid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   182/198 (91.92%)   185/202 (91.58%)   12/13 (92.31%) 
Blood and lymphatic system disorders       
Anaemia † 1  25/198 (12.63%)  32/202 (15.84%)  1/13 (7.69%) 
Leukopenia † 1  9/198 (4.55%)  11/202 (5.45%)  0/13 (0.00%) 
Neutropenia † 1  12/198 (6.06%)  21/202 (10.40%)  0/13 (0.00%) 
Thrombocytopenia † 1  6/198 (3.03%)  6/202 (2.97%)  1/13 (7.69%) 
Cardiac disorders       
Palpitations † 1  2/198 (1.01%)  1/202 (0.50%)  1/13 (7.69%) 
Pericardial effusion † 1  2/198 (1.01%)  1/202 (0.50%)  1/13 (7.69%) 
Ventricular tachycardia † 1  0/198 (0.00%)  0/202 (0.00%)  1/13 (7.69%) 
Eye disorders       
Vision blurred † 1  4/198 (2.02%)  4/202 (1.98%)  1/13 (7.69%) 
Gastrointestinal disorders       
Abdominal pain † 1  20/198 (10.10%)  15/202 (7.43%)  2/13 (15.38%) 
Abdominal pain upper † 1  12/198 (6.06%)  4/202 (1.98%)  0/13 (0.00%) 
Constipation † 1  43/198 (21.72%)  35/202 (17.33%)  1/13 (7.69%) 
Diarrhoea † 1  39/198 (19.70%)  35/202 (17.33%)  2/13 (15.38%) 
Dry mouth † 1  11/198 (5.56%)  5/202 (2.48%)  0/13 (0.00%) 
Dyspepsia † 1  8/198 (4.04%)  16/202 (7.92%)  1/13 (7.69%) 
Dysphagia † 1  8/198 (4.04%)  7/202 (3.47%)  1/13 (7.69%) 
Gastrooesophageal reflux disease † 1  8/198 (4.04%)  11/202 (5.45%)  1/13 (7.69%) 
Nausea † 1  57/198 (28.79%)  51/202 (25.25%)  3/13 (23.08%) 
Oesophagitis † 1  1/198 (0.51%)  4/202 (1.98%)  1/13 (7.69%) 
Oral disorder † 1  2/198 (1.01%)  1/202 (0.50%)  1/13 (7.69%) 
Stomatitis † 1  20/198 (10.10%)  8/202 (3.96%)  2/13 (15.38%) 
Swollen tongue † 1  0/198 (0.00%)  0/202 (0.00%)  1/13 (7.69%) 
Vomiting † 1  30/198 (15.15%)  33/202 (16.34%)  4/13 (30.77%) 
General disorders       
Asthenia † 1  12/198 (6.06%)  15/202 (7.43%)  1/13 (7.69%) 
Chills † 1  10/198 (5.05%)  9/202 (4.46%)  0/13 (0.00%) 
Fatigue † 1  60/198 (30.30%)  68/202 (33.66%)  3/13 (23.08%) 
Oedema † 1  3/198 (1.52%)  3/202 (1.49%)  1/13 (7.69%) 
Oedema peripheral † 1  26/198 (13.13%)  26/202 (12.87%)  3/13 (23.08%) 
Pain † 1  15/198 (7.58%)  11/202 (5.45%)  0/13 (0.00%) 
Pyrexia † 1  18/198 (9.09%)  21/202 (10.40%)  1/13 (7.69%) 
Infections and infestations       
Nasopharyngitis † 1  14/198 (7.07%)  13/202 (6.44%)  0/13 (0.00%) 
Oral herpes † 1  3/198 (1.52%)  1/202 (0.50%)  2/13 (15.38%) 
Sinusitis † 1  11/198 (5.56%)  18/202 (8.91%)  2/13 (15.38%) 
Tooth infection † 1  3/198 (1.52%)  1/202 (0.50%)  1/13 (7.69%) 
Upper respiratory tract infection † 1  18/198 (9.09%)  23/202 (11.39%)  1/13 (7.69%) 
Urinary tract infection † 1  15/198 (7.58%)  23/202 (11.39%)  2/13 (15.38%) 
Injury, poisoning and procedural complications       
Arthropod bite † 1  1/198 (0.51%)  3/202 (1.49%)  1/13 (7.69%) 
Foot fracture † 1  0/198 (0.00%)  0/202 (0.00%)  1/13 (7.69%) 
Laceration † 1  1/198 (0.51%)  2/202 (0.99%)  1/13 (7.69%) 
Ligament sprain † 1  2/198 (1.01%)  0/202 (0.00%)  1/13 (7.69%) 
Rib fracture † 1  2/198 (1.01%)  4/202 (1.98%)  1/13 (7.69%) 
Investigations       
Alanine aminotransferase increased † 1  8/198 (4.04%)  9/202 (4.46%)  1/13 (7.69%) 
Aspartate aminotransferase increased † 1  13/198 (6.57%)  9/202 (4.46%)  2/13 (15.38%) 
Blood albumin decreased † 1  2/198 (1.01%)  0/202 (0.00%)  1/13 (7.69%) 
Blood alkaline phosphatase increased † 1  15/198 (7.58%)  9/202 (4.46%)  2/13 (15.38%) 
Blood bilirubin increased † 1  3/198 (1.52%)  2/202 (0.99%)  1/13 (7.69%) 
Blood cholesterol increased † 1  0/198 (0.00%)  0/202 (0.00%)  1/13 (7.69%) 
Blood creatinine increased † 1  10/198 (5.05%)  4/202 (1.98%)  2/13 (15.38%) 
Blood glucose increased † 1  3/198 (1.52%)  2/202 (0.99%)  1/13 (7.69%) 
Blood lactate dehydrogenase increased † 1  7/198 (3.54%)  7/202 (3.47%)  1/13 (7.69%) 
Blood potassium decreased † 1  3/198 (1.52%)  3/202 (1.49%)  2/13 (15.38%) 
Blood urea increased † 1  3/198 (1.52%)  1/202 (0.50%)  1/13 (7.69%) 
Liver function test abnormal † 1  3/198 (1.52%)  2/202 (0.99%)  1/13 (7.69%) 
Red blood cell count decreased † 1  1/198 (0.51%)  1/202 (0.50%)  1/13 (7.69%) 
Serum ferritin decreased † 1  0/198 (0.00%)  0/202 (0.00%)  1/13 (7.69%) 
Weight decreased † 1  15/198 (7.58%)  18/202 (8.91%)  1/13 (7.69%) 
Weight increased † 1  4/198 (2.02%)  4/202 (1.98%)  1/13 (7.69%) 
Metabolism and nutrition disorders       
Decreased appetite † 1  31/198 (15.66%)  27/202 (13.37%)  0/13 (0.00%) 
Dehydration † 1  8/198 (4.04%)  9/202 (4.46%)  1/13 (7.69%) 
Diabetes mellitus † 1  1/198 (0.51%)  1/202 (0.50%)  1/13 (7.69%) 
Hypocalcaemia † 1  3/198 (1.52%)  3/202 (1.49%)  1/13 (7.69%) 
Hypoglycaemia † 1  0/198 (0.00%)  2/202 (0.99%)  1/13 (7.69%) 
Hypokalaemia † 1  19/198 (9.60%)  20/202 (9.90%)  1/13 (7.69%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  65/198 (32.83%)  56/202 (27.72%)  6/13 (46.15%) 
Back pain † 1  52/198 (26.26%)  38/202 (18.81%)  2/13 (15.38%) 
Bone pain † 1  18/198 (9.09%)  20/202 (9.90%)  1/13 (7.69%) 
Muscle spasms † 1  15/198 (7.58%)  18/202 (8.91%)  1/13 (7.69%) 
Muscular weakness † 1  4/198 (2.02%)  6/202 (2.97%)  1/13 (7.69%) 
Musculoskeletal chest pain † 1  29/198 (14.65%)  25/202 (12.38%)  2/13 (15.38%) 
Musculoskeletal pain † 1  32/198 (16.16%)  30/202 (14.85%)  2/13 (15.38%) 
Myalgia † 1  14/198 (7.07%)  15/202 (7.43%)  1/13 (7.69%) 
Neck pain † 1  8/198 (4.04%)  12/202 (5.94%)  0/13 (0.00%) 
Pain in extremity † 1  49/198 (24.75%)  48/202 (23.76%)  3/13 (23.08%) 
Nervous system disorders       
Balance disorder † 1  6/198 (3.03%)  5/202 (2.48%)  1/13 (7.69%) 
Dizziness † 1  24/198 (12.12%)  18/202 (8.91%)  1/13 (7.69%) 
Headache † 1  33/198 (16.67%)  34/202 (16.83%)  1/13 (7.69%) 
Hypersomnia † 1  0/198 (0.00%)  0/202 (0.00%)  1/13 (7.69%) 
Hypoaesthesia † 1  11/198 (5.56%)  12/202 (5.94%)  1/13 (7.69%) 
Migraine † 1  0/198 (0.00%)  1/202 (0.50%)  1/13 (7.69%) 
Neuralgia † 1  1/198 (0.51%)  4/202 (1.98%)  1/13 (7.69%) 
Neuropathy peripheral † 1  20/198 (10.10%)  21/202 (10.40%)  3/13 (23.08%) 
Paraesthesia † 1  13/198 (6.57%)  12/202 (5.94%)  0/13 (0.00%) 
Peripheral sensory neuropathy † 1  9/198 (4.55%)  7/202 (3.47%)  1/13 (7.69%) 
Restless legs syndrome † 1  1/198 (0.51%)  0/202 (0.00%)  1/13 (7.69%) 
Somnolence † 1  2/198 (1.01%)  3/202 (1.49%)  1/13 (7.69%) 
Psychiatric disorders       
Anxiety † 1  15/198 (7.58%)  11/202 (5.45%)  2/13 (15.38%) 
Depression † 1  13/198 (6.57%)  8/202 (3.96%)  0/13 (0.00%) 
Insomnia † 1  18/198 (9.09%)  19/202 (9.41%)  2/13 (15.38%) 
Renal and urinary disorders       
Pollakiuria † 1  1/198 (0.51%)  4/202 (1.98%)  1/13 (7.69%) 
Reproductive system and breast disorders       
Vaginal discharge † 1  0/198 (0.00%)  2/202 (0.99%)  2/13 (15.38%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1  22/198 (11.11%)  27/202 (13.37%)  1/13 (7.69%) 
Dyspnoea † 1  32/198 (16.16%)  26/202 (12.87%)  2/13 (15.38%) 
Epistaxis † 1  12/198 (6.06%)  11/202 (5.45%)  0/13 (0.00%) 
Oropharyngeal pain † 1  10/198 (5.05%)  8/202 (3.96%)  1/13 (7.69%) 
Pleural effusion † 1  9/198 (4.55%)  13/202 (6.44%)  1/13 (7.69%) 
Sleep apnoea syndrome † 1  2/198 (1.01%)  2/202 (0.99%)  1/13 (7.69%) 
Skin and subcutaneous tissue disorders       
Alopecia † 1  11/198 (5.56%)  10/202 (4.95%)  1/13 (7.69%) 
Night sweats † 1  6/198 (3.03%)  6/202 (2.97%)  1/13 (7.69%) 
Palmar-plantar erythrodysaesthesia syndrome † 1  6/198 (3.03%)  14/202 (6.93%)  0/13 (0.00%) 
Pruritus † 1  7/198 (3.54%)  11/202 (5.45%)  0/13 (0.00%) 
Pruritus generalised † 1  0/198 (0.00%)  1/202 (0.50%)  1/13 (7.69%) 
Rash † 1  18/198 (9.09%)  14/202 (6.93%)  1/13 (7.69%) 
Vascular disorders       
Aortic aneurysm † 1  0/198 (0.00%)  0/202 (0.00%)  1/13 (7.69%) 
Deep vein thrombosis † 1  3/198 (1.52%)  1/202 (0.50%)  1/13 (7.69%) 
Hot flush † 1  13/198 (6.57%)  11/202 (5.45%)  1/13 (7.69%) 
Hypertension † 1  11/198 (5.56%)  12/202 (5.94%)  2/13 (15.38%) 
Lymphoedema † 1  6/198 (3.03%)  8/202 (3.96%)  2/13 (15.38%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
[Not Specified]
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 or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00320710    
Other Study ID Numbers: CZOL446E2352
First Submitted: April 28, 2006
First Posted: May 3, 2006
Results First Submitted: July 8, 2014
Results First Posted: August 4, 2014
Last Update Posted: August 22, 2014