A Multiple Myeloma Trial in Patients With Bone Metastases | NCT00104104

ID	Type	Description	Link
US97

Label	Type	Description	Intervention Names
15 Minute Infusion	Experimental	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks	Drug: zoledronic acid
30 Minute Infusion	Experimental	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks.	Drug: zoledronic acid

Name	Type	Description	Arm Group Labels	Other Names
zoledronic acid	Drug	4 mg zoledronic acid in 250 mL of calcium-free solution (i.e., 0.9% sodium chloride or 5% glucose) administered intravenously.	15 Minute Infusion

Measure	Description	Time Frame
The Number of Participants With a Significant Increase in Serum Creatinine at 12 Months	The primary renal safety endpoint was the number of participants with a clinically relevant increase in serum creatinine at 12 months. Serum creatinine was determined prior to each zoledronic acid infusion for all Participants and was considered to be significantly increased if there was an increase of 0.5 mg/dL or more or a doubling of the baseline serum creatinine value.	Baseline and 12 Months
The Number of Participants With Disease Progression		24 Months

Measure	Description	Time Frame
The Number of Participants With a Significant Increase in Serum Creatinine at 24 Months	Serum Creatinine was considered to be significantly increased if there was an increase of 0.5 mg/dL or more or a doubling of the baseline serum creatinine value.	Baseline and 24 Months
Time to First Significant Increase in Serum Creatinine

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Hematology Oncology Specialists		Huntsville	Alabama	35801	United States
Palo Verde Hematology Oncology

Label	URL
Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.	View source

ID	Title	Description
FG000	15 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Number of Participants With a Significant Increase in Serum Creatinine at 12 Months

The primary renal safety endpoint was the number of participants with a clinically relevant increase in serum creatinine at 12 months. Serum creatinine was determined prior to each zoledronic acid infusion for all Participants and was considered to be significantly increased if there was an increase of 0.5 mg/dL or more or a doubling of the baseline serum creatinine value.

Safety Population: enrolled patients who received at least one dose of study medication, exluding site 74.

Posted

Number

Participants

Baseline and 12 Months

ID	Title	Description
OG000	15 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks.
OG001	30 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks.

Units	Counts
Participants	OG00085 OG00184

Title

Denominators

Categories

Title	Measurements
	OG00017(0.43 to 2.65) OG00113(0.43 to 2.65)

Secondary

The Number of Participants With a Significant Increase in Serum Creatinine at 24 Months

Serum Creatinine was considered to be significantly increased if there was an increase of 0.5 mg/dL or more or a doubling of the baseline serum creatinine value.

Safety Population; enrolled patients who received at least one dose of study medication.

Posted

Number

Participants

Baseline and 24 Months

ID	Title	Description
OG000	15 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks.
OG001	30 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks.

Units	Counts
Participants

Secondary

Time to First Significant Increase in Serum Creatinine

Median time to event in participants who had a clinically relevant increase in serum creatinine.

Safety Population; enrolled patients who received at least one dose of study medication. The medians shown are only for patients who had a significant increase by 24 months.

Posted

Median

Full Range

weeks

Up to 24 months

ID	Title	Description
OG000	15 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks.
OG001	30 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks.

Units	Counts
Participants

Secondary

Zoledronic Acid Concentrations

Samples for drug concentration analysis were drawn at 10 and 15 minutes into the infusion for participants in the 15-minute infusion group and at 25 and 30 minutes into the infusion for patients in the 30-minute infusion group. The mean and median zoledronic acid concentrations were greater in the 15-minute group than in the 30-minute group at both sampling timepoints.

The pharmacokinetic (PK) population was analyzed for zoledronic acid concentration. Participants were considered to be in the PK population if they had evaluable PK data.

Posted

Mean

Standard Deviation

ng/mL

24 months

ID	Title	Description
OG000	15 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks.
OG001	30 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks.

Primary

The Number of Participants With Disease Progression

Safety Population; enrolled patients who received at least one dose of study medication.

Posted

Number

Participants

24 Months

ID	Title	Description
OG000	15 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks.
OG001	30 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG0005 affected85 at risk EG0012 affected84 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0014 affected84 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0013 affected84 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0011 affected84 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Bradycardia	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Cardiac arrest	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Cardiac failure	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Cardiomyopathy	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Left ventricular hypertrophy	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Mitral valve disease	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Mitral valve stenosis	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Myocardial infarction	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Palpitations	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Right atrial dilatation	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Sinus arrhythmia	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Subendocardial ischaemia	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Tachycardia	Cardiac disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Adrenocortical insufficiency acute	Endocrine disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0014 affected84 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Faecal incontinence	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0013 affected84 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0013 affected84 at risk
Asthenia	General disorders	MedDRA 10.X	Systematic Assessment	EG0004 affected85 at risk EG0014 affected84 at risk
Chest discomfort	General disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0010 affected84 at risk
Chest pain	General disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0013 affected84 at risk
Chills	General disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Inflammation	General disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Influenza like illness	General disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Mucosal inflammation	General disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Oedema peripheral	General disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0012 affected84 at risk
Pain	General disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0013 affected84 at risk
Pyrexia	General disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0013 affected84 at risk
Suprapubic pain	General disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Liver disorder	Hepatobiliary disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Abdominal abscess	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Appendicitis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Bacteraemia	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0012 affected84 at risk
Bronchitis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Cellulitis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0013 affected84 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Diverticulitis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Infection	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Meningitis bacterial	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Oral candidiasis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Pneumonia	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0007 affected85 at risk EG0012 affected84 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Sepsis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0012 affected84 at risk
Septic shock	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Compression fracture	Injury, poisoning and procedural complications	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Fractured sacrum	Injury, poisoning and procedural complications	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Ilium fracture	Injury, poisoning and procedural complications	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0012 affected84 at risk
Blood bilirubin increased	Investigations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Blood calcium abnormal	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Blood creatinine abnormal	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Blood creatinine increased	Investigations	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Blood potassium abnormal	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Blood pressure increased	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Blood urea abnormal	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Brain natriuretic peptide increased	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Ejection fraction abnormal	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Electrocardiogram ST segment elevation	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Hepatic enzyme increased	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Platelet count decreased	Investigations	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Acidosis	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0016 affected84 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0010 affected84 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0004 affected85 at risk EG0010 affected84 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0010 affected84 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0014 affected84 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Osteolysis	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0014 affected84 at risk
Acute leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Brain oedema	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Dizziness	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Encephalopathy	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0012 affected84 at risk
Hydrocephalus	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Lethargy	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Loss of consciousness	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Syncope	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0012 affected84 at risk
Confusional state	Psychiatric disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0010 affected84 at risk
Depression	Psychiatric disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Mental status changes	Psychiatric disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0012 affected84 at risk
Suicide attempt	Psychiatric disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Acute prerenal failure	Renal and urinary disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Renal failure	Renal and urinary disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0012 affected84 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 10.X	Systematic Assessment	EG0004 affected85 at risk EG0010 affected84 at risk
Renal failure chronic	Renal and urinary disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0008 affected85 at risk EG0011 affected84 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0012 affected84 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0010 affected84 at risk
Orthopnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0010 affected84 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0014 affected84 at risk
Hypotension	Vascular disorders	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0011 affected84 at risk
Jugular vein distension	Vascular disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0011 affected84 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA 10.X	Systematic Assessment	EG0001 affected85 at risk EG0011 affected84 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG00016 affected85 at risk EG00126 affected84 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG0006 affected85 at risk EG00112 affected84 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 10.X	Systematic Assessment	EG0004 affected85 at risk EG00111 affected84 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0006 affected85 at risk EG0015 affected84 at risk
Constipation	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG00020 affected85 at risk EG00121 affected84 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG00011 affected85 at risk EG00119 affected84 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0005 affected85 at risk EG0015 affected84 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG00016 affected85 at risk EG00125 affected84 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.X	Systematic Assessment	EG0008 affected85 at risk EG00112 affected84 at risk
Asthenia	General disorders	MedDRA 10.X	Systematic Assessment	EG0005 affected85 at risk EG00110 affected84 at risk
Chills	General disorders	MedDRA 10.X	Systematic Assessment	EG0006 affected85 at risk EG0017 affected84 at risk
Fatigue	General disorders	MedDRA 10.X	Systematic Assessment	EG00030 affected85 at risk EG00141 affected84 at risk
Oedema	General disorders	MedDRA 10.X	Systematic Assessment	EG0005 affected85 at risk EG0015 affected84 at risk
Oedema peripheral	General disorders	MedDRA 10.X	Systematic Assessment	EG00013 affected85 at risk EG00119 affected84 at risk
Pain	General disorders	MedDRA 10.X	Systematic Assessment	EG0006 affected85 at risk EG0017 affected84 at risk
Pyrexia	General disorders	MedDRA 10.X	Systematic Assessment	EG00014 affected85 at risk EG00116 affected84 at risk
Bronchitis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0015 affected84 at risk
Herpes zoster	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0006 affected85 at risk EG0016 affected84 at risk
Pneumonia	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0005 affected85 at risk EG0015 affected84 at risk
Sinusitis	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG0007 affected85 at risk EG0018 affected84 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 10.X	Systematic Assessment	EG00013 affected85 at risk EG00113 affected84 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0017 affected84 at risk
Weight decreased	Investigations	MedDRA 10.X	Systematic Assessment	EG0006 affected85 at risk EG0013 affected84 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0008 affected85 at risk EG0019 affected84 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0006 affected85 at risk EG0015 affected84 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0015 affected84 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0007 affected85 at risk EG0017 affected84 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0008 affected85 at risk EG00113 affected84 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 10.X	Systematic Assessment	EG0000 affected85 at risk EG0016 affected84 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG00010 affected85 at risk EG00116 affected84 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG00017 affected85 at risk EG00116 affected84 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG00010 affected85 at risk EG00111 affected84 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0004 affected85 at risk EG0016 affected84 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0005 affected85 at risk EG0017 affected84 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0016 affected84 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0007 affected85 at risk EG0016 affected84 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0016 affected84 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG00013 affected85 at risk EG00112 affected84 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0015 affected84 at risk
Dizziness	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG00010 affected85 at risk EG00110 affected84 at risk
Dysgeusia	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0004 affected85 at risk EG0016 affected84 at risk
Headache	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0008 affected85 at risk EG0018 affected84 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG00010 affected85 at risk EG0013 affected84 at risk
Neuropathy	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0009 affected85 at risk EG0016 affected84 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0007 affected85 at risk EG00115 affected84 at risk
Tremor	Nervous system disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0015 affected84 at risk
Anxiety	Psychiatric disorders	MedDRA 10.X	Systematic Assessment	EG0006 affected85 at risk EG0014 affected84 at risk
Depression	Psychiatric disorders	MedDRA 10.X	Systematic Assessment	EG0009 affected85 at risk EG0015 affected84 at risk
Insomnia	Psychiatric disorders	MedDRA 10.X	Systematic Assessment	EG00010 affected85 at risk EG00114 affected84 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG00013 affected85 at risk EG00114 affected84 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG00010 affected85 at risk EG00116 affected84 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0017 affected84 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 10.X	Systematic Assessment	EG0005 affected85 at risk EG0015 affected84 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 10.X	Systematic Assessment	EG0009 affected85 at risk EG00112 affected84 at risk
Hot flush	Vascular disorders	MedDRA 10.X	Systematic Assessment	EG0003 affected85 at risk EG0016 affected84 at risk
Hypertension	Vascular disorders	MedDRA 10.X	Systematic Assessment	EG0002 affected85 at risk EG0016 affected84 at risk
Hypotension	Vascular disorders	MedDRA 10.X	Systematic Assessment	EG0004 affected85 at risk EG0017 affected84 at risk

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D004164	Diphosphonates
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	15 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks.
BG001	30 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	15 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks.			30	85	74	85
EG001	30 - Minute Infusion	Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks.			35	84	76	84