Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of... | NCT01023958

Status Module

Label	Type	Description	Intervention Names
single arm	Experimental	open label	Drug: BI 6727, IV infusion

Name	Type	Description	Arm Group Labels	Other Names
BI 6727, IV infusion	Drug	phase II	single arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Tumour Response According to RECIST Criteria	Objective tumor response, defined as complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.	From first drug administration until end of study, up to 2 years

Secondary Outcomes

Measure	Description	Time Frame
Progression-free Survival	Progression-free survival (PFS) is the time from first treatment to the occurrence of tumor progression or death, whichever occurs first. Disease progression is defined according to the RECIST guideline but also includes the investigators' assessment which may, in some cases, include only clinical progression (deterioration of general health status per investigator). PFS was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals. Patients without evidence of disease progression were to be censored at the last image date.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Histologically or cytologically confirmed urothelial cancer of the bladder, ureters or renal pelvis.
Patients with stage III, IV or recurrent urothelial cancer of the bladder, ureter or renal pelvis after failure or recurrence after first line or adjuvant/neoadjuvant chemotherapy. Recurrence is defined as relapse within 2 years after cessation of prior first-line chemotherapy.
Male or female patient aged 18 years or older
Life expectancy of at least three (3) months
Eastern Co-operative Oncology Group performance score of 2 or less
At least one target tumor lesion that has not been irradiated within the past three months and that can accurately be measured by magnetic resonance imaging (MRI) or computed tomography (CT) in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT
The patient must have given written informed consent prior to inclusion into the trial which must be consistent with the International Conference on Harmonization, Good Clinical Practice (ICH-GCP) and local legislation

Exclusion criteria:

More than one prior regimen of chemotherapy including prior adjuvant therapy
Brain metastases
Patients with bone metastasis as the only site of disease are excluded
Serious illness or organ system dysfunction, which in the opinion of the investigator, would either compromise patient safety, interfere with the evaluation of the safety of the test drug or limit compliance with trial requirements.
QTc prolongation deemed clinically relevant by the investigator
Second malignancy currently requiring active therapy
Other active malignancy diagnosed within the past 3 years (other than non melanomatous skin cancer and cervical intraepithelial neoplasia)
Absolute neutrophil count (ANC) <1,500/µl
Platelet count <100,000/µl
Hemoglobin <9 g/dl
Total bilirubin >1.5 mg/dl
Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >2.5 x ULN, or aspartate amino transferase (AST) and/or alanine amino transferase (ALT) >5 x ULN in case of known liver metastases
Serum creatinine >1.5 x ULN
Chemo-, Radio- or immunotherapy within the past 4 weeks. This does not apply to steroids and bisphosphonates.
Active infectious disease, or HIV, Hepatitis-B or -C infection
Active drug or alcohol abuse
Women and men who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial
Pregnancy or breast feeding
Treatment with any investigational drug within the past 4 weeks or within less than four half-life times of the investigational drug before treatment with the trial drug and/or persistence of toxicities of prior anticancer therapies which are deemed to be clinically relevant.
Prior treatment with Polo-like kinase 1 (Plk1) inhibitor
Patient unable to comply with the protocol
Any known hypersensitivity to the trial drugs or their excipients

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1230.2.5 Boehringer Ingelheim Investigational Site		Beverly Hills	California		United States
1230.2.10 Boehringer Ingelheim Investigational Site

PubMed Identifier	Type	Citation	Retractions
24339028	Derived	Stadler WM, Vaughn DJ, Sonpavde G, Vogelzang NJ, Tagawa ST, Petrylak DP, Rosen P, Lin CC, Mahoney J, Modi S, Lee P, Ernstoff MS, Su WC, Spira A, Pilz K, Vinisko R, Schloss C, Fritsch H, Zhao C, Carducci MA. An open-label, single-arm, phase 2 trial of the Polo-like kinase inhibitor volasertib (BI 6727) in patients with locally advanced or metastatic urothelial cancer. Cancer. 2014 Apr 1;120(7):976-82. doi: 10.1002/cncr.28519. Epub 2013 Dec 11.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Tumour Response According to RECIST Criteria

Objective tumor response, defined as complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

Posted

Number

95% Confidence Interval

Percentage of participants

From first drug administration until end of study, up to 2 years

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG00050

Title

Denominators

Categories

Title	Measurements
	OG00014.0(5.8 to 26.7)

Secondary

Progression-free Survival

Progression-free survival (PFS) is the time from first treatment to the occurrence of tumor progression or death, whichever occurs first. Disease progression is defined according to the RECIST guideline but also includes the investigators' assessment which may, in some cases, include only clinical progression (deterioration of general health status per investigator). PFS was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals.

Patients without evidence of disease progression were to be censored at the last image date.

Posted

Median

95% Confidence Interval

Weeks

Time from first treatment to the occurrence of tumor progression or death, up to 2 years

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants

Secondary

Overall Survival

Overall survival (OS) is the time from first infusion to death. Patients who were alive at the time of analysis or lost to follow-up were censored at the last follow-up date when they were known to be alive.

Overall survival was analyzed with the Kaplan-Meier curve. Greenwood's variance estimate was used to form confidence intervals.

Posted

Median

95% Confidence Interval

Months

Time from first infusion to death, up to 2 years

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Duration of Overall Response

The duration of overall response is measured from the time of first response (CR or PR) to progression or death whichever occurs first.

Posted

Median

Full Range

Weeks

From the time of first response (CR or PR) to progression or death, up to 2 years

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Disease Control Rate

Disease control rate. Disease control is defined as having a best overall response of complete response (CR), partial response (PR) or stable disease (SD).

Posted

Number

95% Confidence Interval

Percentage of participants

From first drug administration until end of study, up to 2 years

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Duration of Disease Control

Disease control is defined as having a best overall response of CR, PR, or SD. The duration of disease control is measured from the time of first response to progression or death whichever occurs first.

Patients who achieved disease control in the TS.

Posted

Median

Full Range

Weeks

Time of first response to progression or death, up to 2 years

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

AUC0-∞ of Volasertib

Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of volasertib

Pharmacokinetic set (PKS) including patients with analyzable data for this endpoint.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Cmax of Volasertib

Maximum measured concentration in plasma (Cmax) of volasertib

PKS including patients with analyzable data for this endpoint.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

t1/2 of Volasertib

Terminal half-life (t1/2) of volasertib

PKS including patients with analyzable data for this endpoint.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours

5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

CL of Volasertib

Total plasma clearance after intravascular administration (CL) of volasertib

PKS including patients with analyzable data for this endpoint.

Posted

Geometric Mean

Geometric Coefficient of Variation

mL/min

5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Vss of Volasertib

Apparent volume of distribution at steady state following intravascular administration (Vss) of volasertib

PKS including patients with analyzable data for this endpoint.

Posted

Geometric Mean

Geometric Coefficient of Variation

Litres

5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Tmax of Volasertib

Time from dosing to maximum measured concentration (Tmax) of volasertib

PKS including patients with analyzable data for this endpoint.

Posted

Median

Full Range

Hours

5 mins before start of drug infusion and 2h, 3h, 6h, 24h, 168h and 336h after start of drug infusion

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Occurrence and Intensity of AE's Graded According to CTCAE

Occurrence and intensity of adverse events (AEs) graded according to Common Toxicity Criteria of Adverse Events (CTCAE).

The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).

Posted

Number

Percentage of participants

From first drug administration until end of study, up to 2 years

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Occurrence of Unacceptable Toxicity

Occurrence of unacceptable toxicity is defined by CTCAE as as drug related CTCAE Grade 3 or greater non-hematological toxicity (except emesis or diarrhea responding to supportive treatment); drug-related CTCAE Grade 4 neutropenia for seven or more days and / or complicated by infection; or drug-related CTCAE Grade 4 thrombocytopenia.

Posted

Number

Percentage of participants

From first drug administration up to 21 days after final administration, up to 2 years

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: Haemoglobin

Difference from baseline in laboratory parameter Haemoglobin

TS. Results displayed for patients with available haemoglobin data.

Posted

Mean

Standard Deviation

g/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: White Blood Cell Count

Difference from baseline in laboratory parameter white blood cell count

TS. Results displayed for patients with available white blood cell count data.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: Platelets

Difference from baseline in laboratory parameter Platelets

TS. Results displayed for patients with available platelets data.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: Neutrophils

Difference from baseline in laboratory parameter Neutrophils

TS. Results displayed for patients with available neutrophils data.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: Lymphocytes

Difference from baseline in laboratory parameter Lymphocytes

TS. Results displayed for patients with available lymphocytes data.

Posted

Mean

Standard Deviation

10^9 cells/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: AST/GOT, SGOT

Difference from baseline in laboratory parameter Aspartate aminotransferase(AST)/GOT, SGOT

TS. Results displayed for patients with available AST/GOT, SGOT data.

Posted

Mean

Standard Deviation

U/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: ALT/GPT, SGPT

Difference from baseline in laboratory parameter Alanine aminotransferase(ALT)/GPT, SGPT

TS. Results displayed for patients with available ALT/GPT, SGPT data.

Posted

Mean

Standard Deviation

U/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: Alkaline Phosphatase

Difference from baseline in laboratory parameter Alkaline phosphatase

TS. Results displayed for patients with available alkaline phosphate data.

Posted

Mean

Standard Deviation

U/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: Creatinine

Difference from baseline in laboratory parameter Creatinine

TS. Results displayed for patients with available creatinine data.

Posted

Mean

Standard Deviation

umol/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Secondary

Laboratory Investigation: Total Bilirubin

Difference from baseline in laboratory parameter total Bilirubin

TS. Results displayed for patients with available total bilirubin data.

Posted

Mean

Standard Deviation

umol/L

Baseline and last value on treatment (up to 2 years)

ID	Title	Description
OG000	Volasertib (BI 6727)	Volasertib (BI 6727) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Single dose, 300 mg as starting dose in first treatment course - possible dose escalation at the beginning of the 2nd course to 350 mg if well tolerated. Repeated administration in patients with clinical benefit until disease progression or intolerability of the study medication

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected50 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Pericardial effusion	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Pyrexia	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Bacteraemia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Gastroenteritis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Perirectal abscess	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Pneumonia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Septic shock	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 affected50 at risk
Urosepsis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Foreign body	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Urostomy complication	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected50 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected50 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected50 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Metastasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0002 affected50 at risk
Convulsion	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Confusional state	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Mental status changes	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0002 affected50 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk
Hypotension	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected50 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG00020 affected50 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0005 affected50 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG00015 affected50 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG00019 affected50 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00016 affected50 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00011 affected50 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00019 affected50 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected50 at risk
Asthenia	General disorders	MedDRA 13.1	Systematic Assessment	EG0005 affected50 at risk
Chest pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Chills	General disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG00028 affected50 at risk
Oedema peripheral	General disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Pyrexia	General disorders	MedDRA 13.1	Systematic Assessment	EG0005 affected50 at risk
Oral candidiasis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0006 affected50 at risk
Blood creatinine increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Weight decreased	Investigations	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG00016 affected50 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected50 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG00011 affected50 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Dizziness	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0007 affected50 at risk
Anxiety	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected50 at risk
Depression	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Insomnia	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected50 at risk
Dysuria	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Renal failure	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG00010 affected50 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0007 affected50 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected50 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.1	Systematic Assessment	EG0003 affected50 at risk

ID	Term
D061605	Administration, Intravenous
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics
D007263	Infusions, Parenteral