Dose Escalation, Combination Chemotherapy Safety Study of... | NCT01188499

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Carboplatin/Paclitaxel + Birinapant	Experimental	Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).	Drug: Birinapant
Irinotecan + Birinapant	Experimental	Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).	Drug: Birinapant
Docetaxel + Birinapant	Experimental	Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).	Drug: Birinapant
Gemcitabine + Birinapant	Experimental	Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).	Drug: Birinapant
Liposomal Doxorubicin + Birinapant	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Birinapant	Drug		Carboplatin/Paclitaxel + Birinapant Docetaxel + Birinapant Gemcitabine + Birinapant Irinotecan + Birinapant Liposomal Doxorubicin + Birinapant

Measure	Description	Time Frame
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability	Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters	1 Cycle (3-4 weeks)

Measure	Description	Time Frame
Evaluation of Anti-tumor Efficacy	Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression	Every 2 cycles
Evaluation of Pharmacokinetics and Translational Biomarkers

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Confirmed advanced or metastatic malignancy for which the proposed chemotherapy regimen is appropriate in the judgment of the Investigator.
Prior therapy in dose-escalation and expansion cohorts:
- Dose-escalation cohorts: Subjects may be naïve or may have received prior therapy with the specific chemotherapeutic agent(s) being recommended in the combination arm, provided the subject did not experience life-threatening toxicity attributed to the specific agent(s).
- Expansion cohorts: Subjects have advanced colorectal cancer that had been previously determined to be KRAS mutant. Subjects naïve to irinotecan may be enrolled, and the KRAS mutation status may be wild type or mutant. Subjects previously treated with an irinotecan containing regimen may be enrolled only if they have been previously determined to be KRAS wild type. The irinotecan regimen must not have been associated with life threatening adverse events.
Subjects evaluated for Arm 5 (liposomal doxorubicin) may not have received >300 mg/m2 cumulative dose of anthracycline.
Life expectancy >3 months.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
Adequate renal function
Adequate hepatic function
Adequate bone marrow function
Women of childbearing potential must have a negative serum pregnancy test.
Women of childbearing potential must agree to use 2 methods of adequate contraception (ie, hormonal and barrier method) prior to enrollment, during the study, and for a period of 30 days following the last dose of TL32711. Males who are sexually active must agree to use a condom during the study and for a period of 30 days following the last dose of TL32711, and if their partner is of childbearing potential, she must agree to use a secondary method of contraception (ie, hormonal, intrauterine device, barrier) during the study and for a period of 30 days following the last dose of TL32711.

Exclusion Criteria:

Recent anti-cancer treatment defined as:
- Standard or investigational anti-cancer therapy within 4 weeks prior to first dose of TL32711. Exception: continued hormonal interventions for prostate cancer.
- Radiation therapy within 2 weeks prior to the first dose of TL32711.
- Major surgery within 4 weeks prior to the first dose of TL32711. Subjects must be well recovered from acute effects of surgery prior to enrollment.
Known or suspected diagnosis of human immunodeficiency virus or chronic active Hepatitis B or C.
Symptomatic or uncontrolled brain metastases requiring current treatment.
Impaired cardiac function or clinically significant cardiac disease
QT interval corrected for heart rate (QTcB) >480 msec (including subjects on medication).
Lack of recovery of prior adverse events to Grade ≤1 severity (NCI CTCAE v4) (except alopecia) due to therapy administered prior to the initiation of study drug dosing.
Nursing or pregnant women.
Known allergy to any of the formulation components of TL32711.
Any concurrent disease and/or medical condition that in the opinion of the Investigator that would prevent the subject's participation, render the subject at excessive risk (including excessive risks due to the toxicity profile of the planned combination chemotherapeutic regimen), or limit the subject's compliance with the protocol's required evaluations.

Name	Affiliation	Role
John N Nemunaitis, MD	Mary Crowley Cancer Research Center	Principal Investigator
Ravi Amaravadi, MD	University of Pennsylvania, Abramson Cancer Center	Principal Investigator
Lainie P Martin, MD	Fox Chase Cancer Center	Principal Investigator
Alex Adjei, MD, PhD	Roswell Park Cancer Institute	Principal Investigator
Patricia LoRusso, DO	Barbara Ann Karmanos Cancer Center	Principal Investigator
Kyriakos P Papadopoulos, MD	South Texas Accelerated Research Therapeutics (START)	Principal Investigator
Zdenka Segota, MD	Holy Cross Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Holy Cross Hospital		Fort Lauderdale	Florida	33308	United States
Barbara Ann Karmanos Cancer Center

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm 1: Carboplatin/Paclitaxel + Birinapant	Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Arm 1: Carboplatin/Paclitaxel + Birinapant	Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
BG001	Arm 2: Irinotecan + Birinapant	Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
BG002	Arm 3: Docetaxel + Birinapant	Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
BG003	Arm 4: Gemcitabine + Birinapant	Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
BG004	Arm 5: Liposomal Doxorubicin + Birinapant	Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG00024 BG00183 BG00233 BG00318 BG00418 BG005176

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

Number of Subjects With Adverse Events as a Measure of Safety and Tolerability

Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters

Posted

Number

participants

1 Cycle (3-4 weeks)

ID	Title	Description
OG000	Arm 1: Carboplatin/Paclitaxel + TL32711	Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
OG001	Arm 2: Irinotecan + TL32711	Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
OG002	Arm 3: Docetaxel + TL32711	Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
OG003	Arm 4: Gemcitabine + TL32711	Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
OG004	Arm 5: Liposomal Doxorubicin	Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.

Units	Counts
Participants	OG00024 OG00183 OG00233 OG003

Title

Denominators

Categories

Title	Measurements
	OG00024 OG00183 OG00233 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003 OG004						Percent	100			2-Sided						Primary objective of safety and tolerability measured by percent participants experiencing at least one adverse event. No formal statistics performed.	No	Superiority or Other

Secondary

Evaluation of Anti-tumor Efficacy

Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression

Intent-to-treat (ITT)

Posted

Number

participants

Every 2 cycles

ID	Title	Description
OG000	Arm 1: Carboplatin/Paclitaxel + TL32711	Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
OG001	Arm 2: Irinotecan + TL32711	Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy
OG002	Arm 3: Docetaxel + TL32711	Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy

Secondary

Evaluation of Pharmacokinetics and Translational Biomarkers

Measurement of TL32711 pharmacokinetics: Maximum plasma concentration (Cmax), area under the curve (AUC), half-life (t1/2) and assessment of translational biomarkers in plasma, PBMC's and tumor biopsies. Gene expression profiling of tumor tissue.

Not Posted

Cycle 1 and Cycle 2

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1: Carboplatin/Paclitaxel + Birinapant	Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy	9	24	24	24
EG001	Arm 2: Irinotecan + Birinapant	Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy	41	83	83	83
EG002	Arm 3: Docetaxel + Birinapant	Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy	16	33	33	33
EG003	Arm 4: Gemcitabine + Birinapant	Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.	13	18	18	18
EG004	Arm 5: Liposomal Doxorubicin + Birinapant	Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.	9	18	18	18

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0013 affected83 at risk EG0022 affected33 at risk EG0031 affected18 at risk EG0041 affected18 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0017 affected83 at risk EG0021 affected33 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0021 affected33 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected83 at risk EG0021 affected33 at risk EG003
Cardiac tamponade	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Stress cardiomyopathy	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pyloric stenosis	Congenital, familial and genetic disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0014 affected83 at risk EG0021 affected33 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected83 at risk EG0020 affected33 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0016 affected83 at risk EG0020 affected33 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Intestinal perforation	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Oesophagitis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Reflux gastritis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0013 affected83 at risk EG0021 affected33 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0015 affected83 at risk EG0020 affected33 at risk EG003
Chest pain	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Death	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Disease progression	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0014 affected83 at risk EG0025 affected33 at risk EG003
Generalized oedema	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Oedema peripheral	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pain	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pyrexia	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0022 affected33 at risk EG003
Bile duct stenosis	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Bronchitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Cholangitis suppurative	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Cystitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Device related infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Empyema	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Escherichia bacteraemia	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Kidney infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pneumonia	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0012 affected83 at risk EG0025 affected33 at risk EG003
Sepsis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0014 affected83 at risk EG0021 affected33 at risk EG003
Septic shock	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0020 affected33 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
International normalised ratio increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0018 affected83 at risk EG0021 affected33 at risk EG003
Failure to thrive	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0022 affected33 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Intracranial tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0014 affected83 at risk EG0020 affected33 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Bronchial fistula	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0014 affected83 at risk EG0021 affected33 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Venous thrombosis limb	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Pancytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected83 at risk EG0020 affected33 at risk EG003
Caecitis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Asthenia	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Fatigue	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Bacterial sepsis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Colon cancer stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Hypotension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0020 affected33 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG00016 affected24 at risk EG00135 affected83 at risk EG00213 affected33 at risk EG00311 affected18 at risk EG0044 affected18 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0017 affected83 at risk EG0021 affected33 at risk EG003
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0018 affected83 at risk EG0020 affected33 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG0007 affected24 at risk EG00123 affected83 at risk EG00210 affected33 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	EG00011 affected24 at risk EG00128 affected83 at risk EG0027 affected33 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Cardiac tamponade	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Cardiomyopathy	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Palpitations	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Stress cardiomyopathy	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0005 affected24 at risk EG0016 affected83 at risk EG0024 affected33 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
External ear pain	Ear and labyrinth disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Hearing impaired	Ear and labyrinth disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Cushingoid	Endocrine disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Arcus lipoides	Eye disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Eye irritation	Eye disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0011 affected83 at risk EG0024 affected33 at risk EG003
Vision blurred	Eye disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0012 affected83 at risk EG0022 affected33 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0013 affected83 at risk EG0024 affected33 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG00132 affected83 at risk EG0025 affected33 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG0019 affected83 at risk EG0025 affected33 at risk EG003
Abdominal tenderness	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0017 affected83 at risk EG0024 affected33 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00010 affected24 at risk EG00125 affected83 at risk EG00215 affected33 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0006 affected24 at risk EG00158 affected83 at risk EG00212 affected33 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0017 affected83 at risk EG0024 affected33 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0016 affected83 at risk EG0020 affected33 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0023 affected33 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0021 affected33 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Mucous stools	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG00014 affected24 at risk EG00162 affected83 at risk EG00216 affected33 at risk EG003
Oesophagitis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0014 affected83 at risk EG0023 affected33 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Reflux gastritis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG00111 affected83 at risk EG0025 affected33 at risk EG003
Tongue ulceration	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0008 affected24 at risk EG00147 affected83 at risk EG0029 affected33 at risk EG003
Asthenia	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0009 affected24 at risk EG00123 affected83 at risk EG00210 affected33 at risk EG003
Catheter site reaction	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Chest discomfort	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Chest pain	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0013 affected83 at risk EG0020 affected33 at risk EG003
Chills	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0006 affected24 at risk EG00114 affected83 at risk EG0024 affected33 at risk EG003
Device occlusion	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0015 affected83 at risk EG0022 affected33 at risk EG003
Disease progression	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0014 affected83 at risk EG0025 affected33 at risk EG003
Early satiety	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected83 at risk EG0022 affected33 at risk EG003
Face oedema	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Fatigue	General disorders	MedDRA 13.1	Non-systematic Assessment	EG00017 affected24 at risk EG00157 affected83 at risk EG00221 affected33 at risk EG003
Generalized oedema	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Influenza like illness	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Infusion related reaction	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Infusion site reaction	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Localised oedema	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Malaise	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Mucosal inflammation	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG00210 affected33 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Oedema peripheral	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0009 affected24 at risk EG00128 affected83 at risk EG00215 affected33 at risk EG003
Pain	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0013 affected83 at risk EG0022 affected33 at risk EG003
Pyrexia	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0006 affected24 at risk EG00116 affected83 at risk EG0026 affected33 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0022 affected33 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Bronchitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Candidiasis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0016 affected83 at risk EG0025 affected33 at risk EG003
Cellulitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Cystitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Device related infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Empyema	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Folliculitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Fungal infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Kidney infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Pneumonia	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG0013 affected83 at risk EG0023 affected33 at risk EG003
Rhinitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0016 affected83 at risk EG0023 affected33 at risk EG003
Sepsis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0014 affected83 at risk EG0021 affected33 at risk EG003
Septic shock	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Sinusitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0011 affected83 at risk EG0022 affected33 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0015 affected83 at risk EG0023 affected33 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG00112 affected83 at risk EG0023 affected33 at risk EG003
Urosepsis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Vaginal infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Vulvovaginal mycotic infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0015 affected83 at risk EG0021 affected33 at risk EG003
Excoriation	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0013 affected83 at risk EG0021 affected33 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Feeding tube complication	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Post procedural oedema	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0014 affected83 at risk EG0022 affected33 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0016 affected83 at risk EG0022 affected33 at risk EG003
Bacterial test positive	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0016 affected83 at risk EG0021 affected33 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0018 affected83 at risk EG0020 affected33 at risk EG003
Blood creatinine increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG00111 affected83 at risk EG0023 affected33 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0017 affected83 at risk EG0025 affected33 at risk EG003
Blood urea increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0015 affected83 at risk EG0023 affected33 at risk EG003
Blood uric acid increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected83 at risk EG0022 affected33 at risk EG003
Brain natriuretic peptide increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0022 affected33 at risk EG003
Breath sounds abnormal	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0014 affected83 at risk EG0026 affected33 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0018 affected83 at risk EG0024 affected33 at risk EG003
Haptoglobin increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Heart rate irregular	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
International normalised ratio increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0017 affected83 at risk EG0022 affected33 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0016 affected83 at risk EG0021 affected33 at risk EG003
Occult blood positive	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Platelet count decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG0014 affected83 at risk EG0020 affected33 at risk EG003
Pulmonary percussion test abnormality	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Urine analysis abnormal	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Urine bilirubin increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Urine ketone body present	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Urine leukocyte esterase positive	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Urine output decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Urine output increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Urobilinogen urine increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Vitamin D decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0022 affected33 at risk EG003
Weight decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG00116 affected83 at risk EG0023 affected33 at risk EG003
Weight increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
White blood cell count decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG00110 affected83 at risk EG0020 affected33 at risk EG003
White blood cell count increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0013 affected83 at risk EG0022 affected33 at risk EG003
White blood cells urine positive	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Cachexia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG00010 affected24 at risk EG00142 affected83 at risk EG00215 affected33 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG00131 affected83 at risk EG0026 affected33 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Fluid retention	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0024 affected33 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0016 affected83 at risk EG0022 affected33 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0016 affected83 at risk EG0020 affected33 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0019 affected83 at risk EG0020 affected33 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0017 affected83 at risk EG0020 affected33 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0006 affected24 at risk EG00120 affected83 at risk EG0028 affected33 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0016 affected83 at risk EG0022 affected33 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG00112 affected83 at risk EG0026 affected33 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0015 affected83 at risk EG0023 affected33 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0007 affected24 at risk EG00110 affected83 at risk EG0027 affected33 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0007 affected24 at risk EG00111 affected83 at risk EG0025 affected33 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0005 affected24 at risk EG0013 affected83 at risk EG0023 affected33 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0012 affected83 at risk EG0023 affected33 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0016 affected83 at risk EG0023 affected33 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0022 affected33 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0018 affected83 at risk EG0021 affected33 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0008 affected24 at risk EG0018 affected83 at risk EG0025 affected33 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0005 affected24 at risk EG0011 affected83 at risk EG0024 affected33 at risk EG003
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0022 affected33 at risk EG003
Balance disorder	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Cognitive disorder	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0013 affected83 at risk EG0020 affected33 at risk EG003
Dizziness	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG00011 affected24 at risk EG00117 affected83 at risk EG0022 affected33 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0016 affected83 at risk EG0026 affected33 at risk EG003
Extensor plantar response	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Headache	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG00114 affected83 at risk EG0021 affected33 at risk EG003
Hyporeflexia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Lethargy	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0013 affected83 at risk EG0021 affected33 at risk EG003
Nerve compression	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Neuralgia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected83 at risk EG0020 affected33 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0007 affected24 at risk EG0011 affected83 at risk EG0027 affected33 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0019 affected83 at risk EG0021 affected33 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Peroneal nerve palsy	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Restless leg syndrome	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Sciatica	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Sinus headache	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Tardive dyskinesia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Tremor	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
VIIth nerve paralysis	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0021 affected33 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0017 affected83 at risk EG0022 affected33 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0017 affected83 at risk EG0023 affected33 at risk EG003
Depression	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG0012 affected83 at risk EG0026 affected33 at risk EG003
Hallucination	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG00110 affected83 at risk EG0021 affected33 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0014 affected83 at risk EG0020 affected33 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0013 affected83 at risk EG0022 affected33 at risk EG003
Urinary tract obstruction	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Genital rash	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Perineal pain	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Vaginal inflammation	Reproductive system and breast disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Bronchial fistula	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0006 affected24 at risk EG00113 affected83 at risk EG0024 affected33 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0006 affected24 at risk EG00119 affected83 at risk EG0027 affected33 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0006 affected24 at risk EG0018 affected83 at risk EG0024 affected33 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0006 affected24 at risk EG0012 affected83 at risk EG0023 affected33 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0014 affected83 at risk EG0020 affected33 at risk EG003
Hypoventilation	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0022 affected33 at risk EG003
Laryngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0012 affected83 at risk EG0020 affected33 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0016 affected83 at risk EG0025 affected33 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0012 affected83 at risk EG0023 affected33 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0022 affected33 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0022 affected33 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0015 affected83 at risk EG0021 affected33 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Rhonchi	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0013 affected83 at risk EG0021 affected33 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Sputum discoloured	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0014 affected83 at risk EG0022 affected33 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG00014 affected24 at risk EG00134 affected83 at risk EG0028 affected33 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0012 affected83 at risk EG0023 affected33 at risk EG003
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0017 affected83 at risk EG0022 affected33 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0022 affected33 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0014 affected83 at risk EG0022 affected33 at risk EG003
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0022 affected33 at risk EG003
Onychomadesis	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0010 affected83 at risk EG0022 affected33 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0022 affected33 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG0019 affected83 at risk EG0023 affected33 at risk EG003
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0021 affected33 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0005 affected24 at risk EG00116 affected83 at risk EG0024 affected33 at risk EG003
Rash follicular	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0021 affected33 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0020 affected33 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0023 affected33 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Skin hypertrophy	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected24 at risk EG0014 affected83 at risk EG0021 affected33 at risk EG003
Flushing	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0004 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Hot flush	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0015 affected83 at risk EG0020 affected33 at risk EG003
Hypertension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0011 affected83 at risk EG0020 affected33 at risk EG003
Hypotension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected24 at risk EG00112 affected83 at risk EG0026 affected33 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected24 at risk EG0012 affected83 at risk EG0021 affected33 at risk EG003
Pallor	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected24 at risk EG0010 affected83 at risk EG0020 affected33 at risk EG003