Trial Outcomes & Findings for 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 (NCT NCT00320710)
NCT ID: NCT00320710
Last Updated: 2014-08-22
Results Overview
An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
416 participants
Primary outcome timeframe
52 weeks
Results posted on
2014-08-22
Participant Flow
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.
Participant milestones
| Measure |
Zoledronic Acid Every (q) 4 Weeks
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 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.
|
Placebo / Zoledronic Acid
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
200
|
203
|
13
|
|
Overall Study
Treated (Safety Set)
|
198
|
202
|
13
|
|
Overall Study
COMPLETED
|
106
|
127
|
8
|
|
Overall Study
NOT COMPLETED
|
94
|
76
|
5
|
Reasons for withdrawal
| Measure |
Zoledronic Acid Every (q) 4 Weeks
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 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.
|
Placebo / Zoledronic Acid
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.
|
|---|---|---|---|
|
Overall Study
Disease progression
|
24
|
19
|
2
|
|
Overall Study
Death
|
10
|
7
|
1
|
|
Overall Study
Administrative problems
|
1
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
20
|
26
|
1
|
|
Overall Study
Protocol Violation
|
6
|
5
|
0
|
|
Overall Study
Abnormal test procedure result(s)
|
2
|
0
|
0
|
|
Overall Study
Abnormal laboratory value(s)
|
12
|
3
|
0
|
|
Overall Study
Adverse Event
|
18
|
14
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=200 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=203 Participants
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.
|
Placebo / Zoledronic Acid
n=13 Participants
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
n=416 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
59.2 years
STANDARD_DEVIATION 11.10 • n=5 Participants
|
58.6 years
STANDARD_DEVIATION 11.15 • n=7 Participants
|
60.8 years
STANDARD_DEVIATION 12.19 • n=5 Participants
|
58.9 years
STANDARD_DEVIATION 11.14 • n=4 Participants
|
|
Sex/Gender, Customized
|
200 participants
n=5 Participants
|
203 participants
n=7 Participants
|
13 participants
n=5 Participants
|
416 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.
Outcome measures
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=200 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=203 Participants
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.
|
|---|---|---|
|
Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE)
|
22 Percentage of participants
|
23.2 Percentage of participants
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
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.
Outcome measures
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=200 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=203 Participants
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.
|
|---|---|---|
|
Time to First SRE
|
NA Days
The median was not estimable because there were too few events to calculate the median.
|
NA Days
The median was not estimable because there were too few events to calculate the median.
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: The population included participants who were in the zoledronic acid q4 weeks and zoledronic acid q12 weeks treatment groups.
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.
Outcome measures
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=200 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=203 Participants
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.
|
|---|---|---|
|
Time to First Individual Type of SRE
Vertebral pathologic fractures
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
|
Time to First Individual Type of SRE
Non-vertebral pathologic fractures
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
|
Time to First Individual Type of SRE
Spinal cord compression
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
|
Time to First Individual Type of SRE
Radiation to bone
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
|
Time to First Individual Type of SRE
Surgery to bone
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
NA Weeks
The median was not estimable because too few events occurred to calculate the median.
|
SECONDARY outcome
Timeframe: baseline, 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=89 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=100 Participants
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.
|
|---|---|---|
|
Change From Baseline in Mean Composite Brief Pain Inventory (BPI) Score
|
0.24 scores on a scale
Standard Deviation 1.976
|
0.31 scores on a scale
Standard Deviation 2.099
|
SECONDARY outcome
Timeframe: baseline, 52 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=94 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=104 Participants
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.
|
|---|---|---|
|
Change From Baseline in Mean Analgesic Score
|
0.5 score
Standard Deviation 1.28
|
0.5 score
Standard Deviation 1.13
|
SECONDARY outcome
Timeframe: baseline, 48 weeksPopulation: 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.
Urine samples were collected to obtain n-telopeptide and creatinine values.
Outcome measures
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=106 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=119 Participants
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.
|
|---|---|---|
|
Change From Baseline in Urinary N-telopeptide / Creatinine Ratio
|
10.612 ratio
Standard Deviation 40.4073
|
14.697 ratio
Standard Deviation 57.7315
|
SECONDARY outcome
Timeframe: baseline, 48 weeksPopulation: 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.
Serum samples were collected to obtain bone specific alkaline phosphatase values.
Outcome measures
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=93 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=105 Participants
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.
|
|---|---|---|
|
Change From Baseline in Serum Bone Specific Alkaline Phosphatase
|
0.797 mcg/L
Standard Deviation 27.8800
|
4.514 mcg/L
Standard Deviation 12.4509
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: This population included all participants who were in the zoledronic acid q 4 weeks and zoledronic acid q 12 weeks treatment groups.
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).
Outcome measures
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=200 Participants
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=203 Participants
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.
|
|---|---|---|
|
Skeletal Morbidity Rate
|
0.46 Number of events per year
Standard Deviation 1.063
|
0.50 Number of events per year
Standard Deviation 1.500
|
Adverse Events
Zoledronic Acid Every (q) 4 Weeks
Serious events: 50 serious events
Other events: 182 other events
Deaths: 0 deaths
Zoledronic Acid q 12 Weeks
Serious events: 51 serious events
Other events: 185 other events
Deaths: 0 deaths
Placebo / Zoledronic Acid
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=198 participants at risk
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=202 participants at risk
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.
|
Placebo / Zoledronic Acid
n=13 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.51%
1/198
|
1.5%
3/202
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.51%
1/198
|
0.99%
2/202
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.0%
2/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Cardiac disorders
Palpitations
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Cardiac disorders
Pericardial effusion
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Cardiac disorders
Tachycardia
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Congenital, familial and genetic disorders
Arteriovenous malformation
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Endocrine disorders
Hypercalcaemia of malignancy
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Eye disorders
Eye swelling
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Abdominal pain
|
1.0%
2/198
|
2.5%
5/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Diarrhoea
|
1.5%
3/198
|
1.5%
3/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Dysphagia
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Haematemesis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Megacolon
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Mesenteric vein thrombosis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Nausea
|
1.0%
2/198
|
0.99%
2/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Oesophagitis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Oral disorder
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Varices oesophageal
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Vomiting
|
1.5%
3/198
|
0.99%
2/202
|
0.00%
0/13
|
|
General disorders
Asthenia
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
General disorders
Disease progression
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
General disorders
Drug withdrawal syndrome
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
General disorders
Fibrosis
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
General disorders
General physical health deterioration
|
1.0%
2/198
|
0.99%
2/202
|
0.00%
0/13
|
|
General disorders
Generalised oedema
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
General disorders
Mucosal inflammation
|
0.00%
0/198
|
0.50%
1/202
|
7.7%
1/13
|
|
General disorders
Oedema peripheral
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
General disorders
Pain
|
1.0%
2/198
|
0.00%
0/202
|
0.00%
0/13
|
|
General disorders
Perforated ulcer
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
General disorders
Pyrexia
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Hepatobiliary disorders
Biliary dilatation
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Hepatobiliary disorders
Hepatic failure
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Infections and infestations
Bronchitis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Infections and infestations
Cellulitis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Infections and infestations
Gastroenteritis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Infections and infestations
Pneumonia
|
2.0%
4/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Infections and infestations
Sepsis
|
1.0%
2/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Infections and infestations
Septic shock
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
1.0%
2/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Injury, poisoning and procedural complications
Comminuted fracture
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/198
|
1.5%
3/202
|
0.00%
0/13
|
|
Investigations
Hepatic enzyme increased
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Investigations
Troponin increased
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Dehydration
|
2.0%
4/198
|
2.0%
4/202
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.51%
1/198
|
0.99%
2/202
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.51%
1/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.0%
2/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw
|
1.0%
2/198
|
0.99%
2/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.51%
1/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
1.5%
3/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/198
|
0.99%
2/202
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Nervous system disorders
Brain mass
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Nervous system disorders
Coma
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Nervous system disorders
Convulsion
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Nervous system disorders
Depressed level of consciousness
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Nervous system disorders
Encephalopathy
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Nervous system disorders
Hemiparesis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Nervous system disorders
Migraine
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Nervous system disorders
Somnolence
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Nervous system disorders
Vasogenic cerebral oedema
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Psychiatric disorders
Acute psychosis
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Psychiatric disorders
Confusional state
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Psychiatric disorders
Delirium
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/198
|
0.99%
2/202
|
0.00%
0/13
|
|
Renal and urinary disorders
Haematuria
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Renal and urinary disorders
Renal failure acute
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.5%
3/198
|
2.5%
5/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.51%
1/198
|
2.0%
4/202
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.0%
2/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.51%
1/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
|
Vascular disorders
Deep vein thrombosis
|
0.51%
1/198
|
0.99%
2/202
|
0.00%
0/13
|
|
Vascular disorders
Hypertension
|
0.00%
0/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Vascular disorders
Hypotension
|
1.0%
2/198
|
0.50%
1/202
|
0.00%
0/13
|
|
Vascular disorders
Orthostatic hypotension
|
0.51%
1/198
|
0.00%
0/202
|
0.00%
0/13
|
Other adverse events
| Measure |
Zoledronic Acid Every (q) 4 Weeks
n=198 participants at risk
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
|
Zoledronic Acid q 12 Weeks
n=202 participants at risk
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.
|
Placebo / Zoledronic Acid
n=13 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
12.6%
25/198
|
15.8%
32/202
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
Leukopenia
|
4.5%
9/198
|
5.4%
11/202
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.1%
12/198
|
10.4%
21/202
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.0%
6/198
|
3.0%
6/202
|
7.7%
1/13
|
|
Cardiac disorders
Palpitations
|
1.0%
2/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Cardiac disorders
Pericardial effusion
|
1.0%
2/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Eye disorders
Vision blurred
|
2.0%
4/198
|
2.0%
4/202
|
7.7%
1/13
|
|
Gastrointestinal disorders
Abdominal pain
|
10.1%
20/198
|
7.4%
15/202
|
15.4%
2/13
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.1%
12/198
|
2.0%
4/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Constipation
|
21.7%
43/198
|
17.3%
35/202
|
7.7%
1/13
|
|
Gastrointestinal disorders
Diarrhoea
|
19.7%
39/198
|
17.3%
35/202
|
15.4%
2/13
|
|
Gastrointestinal disorders
Dry mouth
|
5.6%
11/198
|
2.5%
5/202
|
0.00%
0/13
|
|
Gastrointestinal disorders
Dyspepsia
|
4.0%
8/198
|
7.9%
16/202
|
7.7%
1/13
|
|
Gastrointestinal disorders
Dysphagia
|
4.0%
8/198
|
3.5%
7/202
|
7.7%
1/13
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
4.0%
8/198
|
5.4%
11/202
|
7.7%
1/13
|
|
Gastrointestinal disorders
Nausea
|
28.8%
57/198
|
25.2%
51/202
|
23.1%
3/13
|
|
Gastrointestinal disorders
Oesophagitis
|
0.51%
1/198
|
2.0%
4/202
|
7.7%
1/13
|
|
Gastrointestinal disorders
Oral disorder
|
1.0%
2/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Gastrointestinal disorders
Stomatitis
|
10.1%
20/198
|
4.0%
8/202
|
15.4%
2/13
|
|
Gastrointestinal disorders
Swollen tongue
|
0.00%
0/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Gastrointestinal disorders
Vomiting
|
15.2%
30/198
|
16.3%
33/202
|
30.8%
4/13
|
|
General disorders
Asthenia
|
6.1%
12/198
|
7.4%
15/202
|
7.7%
1/13
|
|
General disorders
Chills
|
5.1%
10/198
|
4.5%
9/202
|
0.00%
0/13
|
|
General disorders
Fatigue
|
30.3%
60/198
|
33.7%
68/202
|
23.1%
3/13
|
|
General disorders
Oedema
|
1.5%
3/198
|
1.5%
3/202
|
7.7%
1/13
|
|
General disorders
Oedema peripheral
|
13.1%
26/198
|
12.9%
26/202
|
23.1%
3/13
|
|
General disorders
Pain
|
7.6%
15/198
|
5.4%
11/202
|
0.00%
0/13
|
|
General disorders
Pyrexia
|
9.1%
18/198
|
10.4%
21/202
|
7.7%
1/13
|
|
Infections and infestations
Nasopharyngitis
|
7.1%
14/198
|
6.4%
13/202
|
0.00%
0/13
|
|
Infections and infestations
Oral herpes
|
1.5%
3/198
|
0.50%
1/202
|
15.4%
2/13
|
|
Infections and infestations
Sinusitis
|
5.6%
11/198
|
8.9%
18/202
|
15.4%
2/13
|
|
Infections and infestations
Tooth infection
|
1.5%
3/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Infections and infestations
Upper respiratory tract infection
|
9.1%
18/198
|
11.4%
23/202
|
7.7%
1/13
|
|
Infections and infestations
Urinary tract infection
|
7.6%
15/198
|
11.4%
23/202
|
15.4%
2/13
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.51%
1/198
|
1.5%
3/202
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Laceration
|
0.51%
1/198
|
0.99%
2/202
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
1.0%
2/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Rib fracture
|
1.0%
2/198
|
2.0%
4/202
|
7.7%
1/13
|
|
Investigations
Alanine aminotransferase increased
|
4.0%
8/198
|
4.5%
9/202
|
7.7%
1/13
|
|
Investigations
Aspartate aminotransferase increased
|
6.6%
13/198
|
4.5%
9/202
|
15.4%
2/13
|
|
Investigations
Blood albumin decreased
|
1.0%
2/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Investigations
Blood alkaline phosphatase increased
|
7.6%
15/198
|
4.5%
9/202
|
15.4%
2/13
|
|
Investigations
Blood bilirubin increased
|
1.5%
3/198
|
0.99%
2/202
|
7.7%
1/13
|
|
Investigations
Blood cholesterol increased
|
0.00%
0/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Investigations
Blood creatinine increased
|
5.1%
10/198
|
2.0%
4/202
|
15.4%
2/13
|
|
Investigations
Blood glucose increased
|
1.5%
3/198
|
0.99%
2/202
|
7.7%
1/13
|
|
Investigations
Blood lactate dehydrogenase increased
|
3.5%
7/198
|
3.5%
7/202
|
7.7%
1/13
|
|
Investigations
Blood potassium decreased
|
1.5%
3/198
|
1.5%
3/202
|
15.4%
2/13
|
|
Investigations
Blood urea increased
|
1.5%
3/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Investigations
Liver function test abnormal
|
1.5%
3/198
|
0.99%
2/202
|
7.7%
1/13
|
|
Investigations
Red blood cell count decreased
|
0.51%
1/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Investigations
Serum ferritin decreased
|
0.00%
0/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Investigations
Weight decreased
|
7.6%
15/198
|
8.9%
18/202
|
7.7%
1/13
|
|
Investigations
Weight increased
|
2.0%
4/198
|
2.0%
4/202
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.7%
31/198
|
13.4%
27/202
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
Dehydration
|
4.0%
8/198
|
4.5%
9/202
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.51%
1/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
1.5%
3/198
|
1.5%
3/202
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/198
|
0.99%
2/202
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.6%
19/198
|
9.9%
20/202
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
32.8%
65/198
|
27.7%
56/202
|
46.2%
6/13
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
26.3%
52/198
|
18.8%
38/202
|
15.4%
2/13
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
9.1%
18/198
|
9.9%
20/202
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.6%
15/198
|
8.9%
18/202
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.0%
4/198
|
3.0%
6/202
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
14.6%
29/198
|
12.4%
25/202
|
15.4%
2/13
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
16.2%
32/198
|
14.9%
30/202
|
15.4%
2/13
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.1%
14/198
|
7.4%
15/202
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
4.0%
8/198
|
5.9%
12/202
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
24.7%
49/198
|
23.8%
48/202
|
23.1%
3/13
|
|
Nervous system disorders
Balance disorder
|
3.0%
6/198
|
2.5%
5/202
|
7.7%
1/13
|
|
Nervous system disorders
Dizziness
|
12.1%
24/198
|
8.9%
18/202
|
7.7%
1/13
|
|
Nervous system disorders
Headache
|
16.7%
33/198
|
16.8%
34/202
|
7.7%
1/13
|
|
Nervous system disorders
Hypersomnia
|
0.00%
0/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Nervous system disorders
Hypoaesthesia
|
5.6%
11/198
|
5.9%
12/202
|
7.7%
1/13
|
|
Nervous system disorders
Migraine
|
0.00%
0/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Nervous system disorders
Neuralgia
|
0.51%
1/198
|
2.0%
4/202
|
7.7%
1/13
|
|
Nervous system disorders
Neuropathy peripheral
|
10.1%
20/198
|
10.4%
21/202
|
23.1%
3/13
|
|
Nervous system disorders
Paraesthesia
|
6.6%
13/198
|
5.9%
12/202
|
0.00%
0/13
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
4.5%
9/198
|
3.5%
7/202
|
7.7%
1/13
|
|
Nervous system disorders
Restless legs syndrome
|
0.51%
1/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Nervous system disorders
Somnolence
|
1.0%
2/198
|
1.5%
3/202
|
7.7%
1/13
|
|
Psychiatric disorders
Anxiety
|
7.6%
15/198
|
5.4%
11/202
|
15.4%
2/13
|
|
Psychiatric disorders
Depression
|
6.6%
13/198
|
4.0%
8/202
|
0.00%
0/13
|
|
Psychiatric disorders
Insomnia
|
9.1%
18/198
|
9.4%
19/202
|
15.4%
2/13
|
|
Renal and urinary disorders
Pollakiuria
|
0.51%
1/198
|
2.0%
4/202
|
7.7%
1/13
|
|
Reproductive system and breast disorders
Vaginal discharge
|
0.00%
0/198
|
0.99%
2/202
|
15.4%
2/13
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.1%
22/198
|
13.4%
27/202
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.2%
32/198
|
12.9%
26/202
|
15.4%
2/13
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.1%
12/198
|
5.4%
11/202
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.1%
10/198
|
4.0%
8/202
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
4.5%
9/198
|
6.4%
13/202
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
1.0%
2/198
|
0.99%
2/202
|
7.7%
1/13
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.6%
11/198
|
5.0%
10/202
|
7.7%
1/13
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
3.0%
6/198
|
3.0%
6/202
|
7.7%
1/13
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
3.0%
6/198
|
6.9%
14/202
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.5%
7/198
|
5.4%
11/202
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.1%
18/198
|
6.9%
14/202
|
7.7%
1/13
|
|
Vascular disorders
Aortic aneurysm
|
0.00%
0/198
|
0.00%
0/202
|
7.7%
1/13
|
|
Vascular disorders
Deep vein thrombosis
|
1.5%
3/198
|
0.50%
1/202
|
7.7%
1/13
|
|
Vascular disorders
Hot flush
|
6.6%
13/198
|
5.4%
11/202
|
7.7%
1/13
|
|
Vascular disorders
Hypertension
|
5.6%
11/198
|
5.9%
12/202
|
15.4%
2/13
|
|
Vascular disorders
Lymphoedema
|
3.0%
6/198
|
4.0%
8/202
|
15.4%
2/13
|
Additional Information
Study Director
Novartis
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER