Trial Outcomes & Findings for A Multiple Myeloma Trial in Patients With Bone Metastases (NCT NCT00104104)

NCT ID: NCT00104104

Last Updated: 2011-06-29

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 179 participants
• Primary outcome timeframe: Baseline and 12 Months
• Results posted on: 2011-06-29

Participant Flow

Participant milestones

Measure	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 - 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.
Overall Study STARTED	90	89
Overall Study Safety Population (Including Site 74)	88	88
Overall Study Safety Population (Excluding Site 74)	85	84
Overall Study COMPLETED	15	17
Overall Study NOT COMPLETED	75	72

Reasons for withdrawal

Measure	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 - 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.
Overall Study Adverse Event	8	8
Overall Study Abnormal laboratory value(s)	20	14
Overall Study Lack of Efficacy	0	3
Overall Study Condition no longer requires study drug	7	4
Overall Study Protocol Violation	5	2
Overall Study Withdrawal by Subject	11	15
Overall Study Lost to Follow-up	3	7
Overall Study Administrative problems	12	13
Overall Study Death	9	6

Baseline Characteristics

A Multiple Myeloma Trial in Patients With Bone Metastases

Baseline characteristics by cohort

Measure	15 - Minute Infusion n=88 Participants 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 - Minute Infusion n=88 Participants 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.	Total n=176 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	39 Participants n=93 Participants	47 Participants n=4 Participants	86 Participants n=27 Participants
Age, Categorical >=65 years	49 Participants n=93 Participants	41 Participants n=4 Participants	90 Participants n=27 Participants
Age Continuous	64.3 years STANDARD_DEVIATION 11.95 • n=93 Participants	64.0 years STANDARD_DEVIATION 11.54 • n=4 Participants	64.1 years STANDARD_DEVIATION 11.7 • n=27 Participants
Sex: Female, Male Female	32 Participants n=93 Participants	39 Participants n=4 Participants	71 Participants n=27 Participants
Sex: Female, Male Male	56 Participants n=93 Participants	49 Participants n=4 Participants	105 Participants n=27 Participants
Race/Ethnicity, Customized Caucasian	70 participants n=93 Participants	69 participants n=4 Participants	139 participants n=27 Participants
Race/Ethnicity, Customized Black	9 participants n=93 Participants	13 participants n=4 Participants	22 participants n=27 Participants
Race/Ethnicity, Customized Asian	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants
Race/Ethnicity, Customized Other	8 participants n=93 Participants	5 participants n=4 Participants	13 participants n=27 Participants
Region of Enrollment United States	88 participants n=93 Participants	88 participants n=4 Participants	176 participants n=27 Participants
Time since diagnosis	12.5 months STANDARD_DEVIATION 24.3 • n=93 Participants	9.7 months STANDARD_DEVIATION 14.1 • n=4 Participants	11.1 months STANDARD_DEVIATION 19.8 • n=27 Participants
Calculated creatinine clearance	87.3 mL/min STANDARD_DEVIATION 32.6 • n=93 Participants	89.3 mL/min STANDARD_DEVIATION 39.5 • n=4 Participants	88.3 mL/min STANDARD_DEVIATION 36.1 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline and 12 Months

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

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.

Outcome measures

Measure	15 - Minute Infusion n=85 Participants 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 - Minute Infusion n=84 Participants 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.
The Number of Participants With a Significant Increase in Serum Creatinine at 12 Months	17 Participants Interval 0.43 to 2.65	13 Participants Interval 0.43 to 2.65

PRIMARY outcome

Timeframe: 24 Months

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

Outcome measures

Measure	15 - Minute Infusion n=85 Participants 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 - Minute Infusion n=84 Participants 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.
The Number of Participants With Disease Progression	28 Participants	20 Participants

SECONDARY outcome

Timeframe: Baseline and 24 Months

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

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.

Outcome measures

Measure	15 - Minute Infusion n=85 Participants 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 - Minute Infusion n=84 Participants 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.
The Number of Participants With a Significant Increase in Serum Creatinine at 24 Months	24 Participants Interval 0.53 to 2.13	23 Participants Interval 0.53 to 2.13

SECONDARY outcome

Timeframe: Up to 24 months

Population: 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.

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

Outcome measures

Measure	15 - Minute Infusion n=24 Participants 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 - Minute Infusion n=23 Participants 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.
Time to First Significant Increase in Serum Creatinine	21.6 weeks Full Range 19.88 • Interval 4.1 to 65.0	24.4 weeks Full Range 31.48 • Interval 2.6 to 93.9

SECONDARY outcome

Timeframe: 24 months

Population: 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.

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.

Outcome measures

Measure	15 - Minute Infusion n=70 Participants 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 - Minute Infusion n=63 Participants 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.
Zoledronic Acid Concentrations First Collection (10 minutes, 25 minutes)	231.1 ng/mL Standard Deviation 185.4	186.3 ng/mL Standard Deviation 54.4
Zoledronic Acid Concentrations Second Collection (15 minutes, 30 minutes)	248.8 ng/mL Standard Deviation 92.0	172.0 ng/mL Standard Deviation 48.3

Adverse Events

15 - Minute Infusion

Serious events: 30 serious events

Other events: 74 other events

Deaths: 0 deaths

30 - Minute Infusion

Serious events: 35 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Measure	15 - Minute Infusion n=85 participants at risk 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 - Minute Infusion n=84 participants at risk 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.
Blood and lymphatic system disorders Anaemia	5.9% 5/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Blood and lymphatic system disorders Febrile neutropenia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	4.8% 4/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Blood and lymphatic system disorders Leukocytosis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Blood and lymphatic system disorders Leukopenia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Arteriosclerosis coronary artery	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Atrial fibrillation	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Atrioventricular block first degree	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Bradycardia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Cardiac arrest	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Cardiac failure	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Cardiac failure congestive	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Cardio-respiratory arrest	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Cardiomyopathy	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Left ventricular hypertrophy	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Mitral valve disease	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Mitral valve stenosis	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Myocardial infarction	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Palpitations	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Right atrial dilatation	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Sinus arrhythmia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Sinus tachycardia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Subendocardial ischaemia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Cardiac disorders Tachycardia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Endocrine disorders Adrenocortical insufficiency acute	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Diarrhoea	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	4.8% 4/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Diverticular perforation	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Dysphagia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Faecal incontinence	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Gastric ulcer	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Nausea	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Vomiting	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Asthenia	4.7% 4/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	4.8% 4/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Chest discomfort	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Chest pain	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Chills	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Inflammation	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Influenza like illness	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Mucosal inflammation	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Oedema peripheral	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Pain	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Pyrexia	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Suprapubic pain	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Hepatobiliary disorders Hepatic failure	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Hepatobiliary disorders Liver disorder	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Immune system disorders Anaphylactic reaction	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Abdominal abscess	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Appendicitis	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Bacteraemia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Bronchitis	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Cellulitis	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Clostridium difficile colitis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Diverticulitis	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Infection	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Meningitis bacterial	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Oral candidiasis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Pneumonia	8.2% 7/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Pneumonia bacterial	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Sepsis	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Septic shock	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Staphylococcal sepsis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Urinary tract infection	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Injury, poisoning and procedural complications Compression fracture	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Injury, poisoning and procedural complications Fall	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Injury, poisoning and procedural complications Fractured sacrum	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Injury, poisoning and procedural complications Ilium fracture	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Injury, poisoning and procedural complications Spinal compression fracture	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Blood bilirubin increased	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Blood calcium abnormal	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Blood creatinine abnormal	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Blood creatinine increased	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Blood potassium abnormal	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Blood pressure increased	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Blood urea abnormal	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Brain natriuretic peptide increased	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Ejection fraction abnormal	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Electrocardiogram ST segment elevation	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Hepatic enzyme increased	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Platelet count decreased	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Acidosis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Decreased appetite	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Dehydration	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Diabetic ketoacidosis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Electrolyte imbalance	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hypercalcaemia	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hyperglycaemia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hypokalaemia	4.7% 4/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hyponatraemia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hypovolaemia	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Malnutrition	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Arthralgia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Back pain	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	4.8% 4/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Groin pain	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Muscular weakness	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Neck pain	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Osteolysis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Osteonecrosis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Pain in extremity	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	4.8% 4/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Brain oedema	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Carotid artery stenosis	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Cerebral haemorrhage	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Cerebral ischaemia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Depressed level of consciousness	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Dizziness	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Encephalopathy	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Hydrocephalus	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Lethargy	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Loss of consciousness	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Metabolic encephalopathy	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Syncope	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Psychiatric disorders Confusional state	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Psychiatric disorders Depression	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Psychiatric disorders Mental status changes	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Psychiatric disorders Suicide attempt	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Renal and urinary disorders Acute prerenal failure	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Renal and urinary disorders Hydronephrosis	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Renal and urinary disorders Renal failure	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Renal and urinary disorders Renal failure acute	4.7% 4/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Renal and urinary disorders Renal failure chronic	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Atelectasis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.4% 8/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	2.4% 2/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Lung infiltration	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Orthopnoea	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	0.00% 0/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Vascular disorders Deep vein thrombosis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	4.8% 4/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Vascular disorders Hypotension	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Vascular disorders Jugular vein distension	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Vascular disorders Jugular vein thrombosis	1.2% 1/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	1.2% 1/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.

Other adverse events

Measure	15 - Minute Infusion n=85 participants at risk 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 - Minute Infusion n=84 participants at risk 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.
Blood and lymphatic system disorders Anaemia	18.8% 16/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	31.0% 26/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Blood and lymphatic system disorders Neutropenia	7.1% 6/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	14.3% 12/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Blood and lymphatic system disorders Thrombocytopenia	4.7% 4/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	13.1% 11/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Abdominal pain	7.1% 6/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Constipation	23.5% 20/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	25.0% 21/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Diarrhoea	12.9% 11/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	22.6% 19/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Dyspepsia	5.9% 5/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Nausea	18.8% 16/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	29.8% 25/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Gastrointestinal disorders Vomiting	9.4% 8/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	14.3% 12/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Asthenia	5.9% 5/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	11.9% 10/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Chills	7.1% 6/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	8.3% 7/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Fatigue	35.3% 30/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	48.8% 41/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Oedema	5.9% 5/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Oedema peripheral	15.3% 13/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	22.6% 19/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Pain	7.1% 6/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	8.3% 7/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
General disorders Pyrexia	16.5% 14/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	19.0% 16/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Bronchitis	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Herpes zoster	7.1% 6/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Pneumonia	5.9% 5/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Sinusitis	8.2% 7/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	9.5% 8/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Infections and infestations Upper respiratory tract infection	15.3% 13/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	15.5% 13/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Injury, poisoning and procedural complications Contusion	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	8.3% 7/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Investigations Weight decreased	7.1% 6/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Anorexia	9.4% 8/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	10.7% 9/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Decreased appetite	7.1% 6/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Dehydration	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hyperglycaemia	8.2% 7/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	8.3% 7/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hypokalaemia	9.4% 8/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	15.5% 13/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Arthralgia	11.8% 10/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	19.0% 16/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Back pain	20.0% 17/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	19.0% 16/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Bone pain	11.8% 10/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	13.1% 11/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Muscle spasms	4.7% 4/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Muscular weakness	5.9% 5/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	8.3% 7/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.2% 7/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Myalgia	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Pain in extremity	15.3% 13/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	14.3% 12/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Musculoskeletal and connective tissue disorders Pain in jaw	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Dizziness	11.8% 10/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	11.9% 10/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Dysgeusia	4.7% 4/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Headache	9.4% 8/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	9.5% 8/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Hypoaesthesia	11.8% 10/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	3.6% 3/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Neuropathy	10.6% 9/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Neuropathy peripheral	8.2% 7/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	17.9% 15/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Nervous system disorders Tremor	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Psychiatric disorders Anxiety	7.1% 6/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	4.8% 4/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Psychiatric disorders Depression	10.6% 9/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Psychiatric disorders Insomnia	11.8% 10/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	16.7% 14/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Cough	15.3% 13/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	16.7% 14/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.8% 10/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	19.0% 16/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	8.3% 7/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	5.9% 5/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	6.0% 5/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Skin and subcutaneous tissue disorders Rash	10.6% 9/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	14.3% 12/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Vascular disorders Hot flush	3.5% 3/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Vascular disorders Hypertension	2.4% 2/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	7.1% 6/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.
Vascular disorders Hypotension	4.7% 4/85 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.	8.3% 7/84 Because of GCP violations at Site 74, post-baseline data from that site are excluded from analyses, leaving 85 patients in the 15-minute infusion group and 84 patients in the 30-minute infusion group.

Additional Information

Study Director

Novatis Pharmaceuticals

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 the trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER