Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Re... | NCT02551991

NCT02551991

ID	Type	Description	Link
2015-003086-28	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
nal-IRI + 5-FU/LV + oxaliplatin	Experimental		Drug: nal-IRI Drug: 5 fluorouracil Drug: Leucovorin Drug: Oxaliplatin

Name	Type	Description	Arm Group Labels	Other Names
nal-IRI	Drug		nal-IRI + 5-FU/LV + oxaliplatin	MM-398
5 fluorouracil

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)	Adverse events (AEs) were considered to be DLTs if they occurred during the safety evaluation period (i.e, 28 days of Cycle 1; or 14 days after the second dose of study treatment if there was a treatment delay) and were deemed related to the study treatment regimen. Any AE that was related to disease progression was not considered a DLT.	From the start of the first study treatment (Cycle 1 Day 1) up to 14 days after the second dose of study treatment, maximum of 42 days

Secondary Outcomes

Measure	Description	Time Frame
Median Progression Free Survival (PFS)	The PFS was defined as the time from date of first study treatment to the first documented radiographical progression of disease (PD), per investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death from any cause, whichever comes first. The PFS was calculated using Kaplan-Meier technique.	RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter (maximum of 278 weeks).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting
Unresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior to screening
At least one tumor lesion measurable by CT or MRI scan (according to RECIST v1.1)
ECOG performance status of 0 or 1 at screening and within 72 hours prior to first dose if first dose occurs more than 72 hours post-screening
Adequate hematological, hepatic, renal and cardiac function
Recovered from the effects of any prior surgery or radiotherapy
Patient has a Karnofsky performance status (KPS) ≥ 70 at Screening, and within 72 hours prior to date of first dose if first dose occurs more than 72 hours after screening (Part 1B only)

Exclusion Criteria:

Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapy
Prior treatment of pancreatic cancer with chemotherapy in adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities present
Uncontrolled Central Nervous System (CNS) metastases
Clinically significant gastrointestinal disorder
History of any second malignancy in the last 3 years. Patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible
Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin, oxaliplatin
Use of strong CYP3A4 or inducers or presence of any other contra indications for irinotecan
Pregnant or breast feeding
Neuroendocrine or acinar pancreatic carcinoma
Serum albumin < 3 g/dL at screening visit and within 72 hours prior to first dose if first dose occurs more than 72 hours post screening
Patients with symptoms and signs of clinically unacceptable deterioration of primary disease at time of screening
Previous treatment with irinotecan-based, nab-paclitaxel-based or gemcitabine-based resulting in disease progression

Contacts/Locations Module

Name	Affiliation	Role
Ipsen Medical Director	Ipsen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of South Alabama		Mobile	Alabama	36604	United States
University of South Alabama - Mobile

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34750990	Derived	Brendel K, Bekaii-Saab T, Boland PM, Dayyani F, Dean A, Macarulla T, Maxwell F, Mody K, Pedret-Dunn A, Wainberg ZA, Zhang B. Population pharmacokinetics of liposomal irinotecan in patients with cancer and exposure-safety analyses in patients with metastatic pancreatic cancer. CPT Pharmacometrics Syst Pharmacol. 2021 Dec;10(12):1550-1563. doi: 10.1002/psp4.12725. Epub 2021 Nov 20.
33957442

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 milligram per square meter (mg/m^2) followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 27, 2019	Apr 21, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Safety population included participants who received at least 1 dose of any study treatment.

Arm/Group Information

ID	Title	Description
BG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
BG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
BG002	Dose Exploration: Cohort -2B	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 85 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
BG003	Dose Exploration: Cohort -3	Participants received irinotecan liposome injection 55 mg/m^2 followed by oxaliplatin 70 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
BG004	Dose Expansion: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 65 years	BG0004 BG0014 BG0023 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0006 BG0014 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG0006 BG0017 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

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

Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)

Adverse events (AEs) were considered to be DLTs if they occurred during the safety evaluation period (i.e, 28 days of Cycle 1; or 14 days after the second dose of study treatment if there was a treatment delay) and were deemed related to the study treatment regimen. Any AE that was related to disease progression was not considered a DLT.

Safety population included participants who received at least 1 dose of any study treatment.

Posted

Count of Participants

Participants

From the start of the first study treatment (Cycle 1 Day 1) up to 14 days after the second dose of study treatment, maximum of 42 days

ID	Title	Description
OG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG002	Dose Exploration: Cohort -2B	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 85 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG003	Dose Exploration: Cohort -3	Participants received irinotecan liposome injection 55 mg/m^2 followed by oxaliplatin 70 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.

Units	Counts
Participants	OG0007 OG0017 OG00210 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002 OG0011 OG0022 OG003

Secondary

Median Progression Free Survival (PFS)

The PFS was defined as the time from date of first study treatment to the first documented radiographical progression of disease (PD), per investigator using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death from any cause, whichever comes first. The PFS was calculated using Kaplan-Meier technique.

Safety population included participants who received at least 1 dose of any study treatment.

Posted

Median

95% Confidence Interval

months

RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter (maximum of 278 weeks).

ID	Title	Description
OG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.

Secondary

Best Overall Response (BOR)

The BOR was defined as the best response (complete response [CR] + partial response [PR] + stable disease [SD]) recorded from the start of study treatment until disease progression or start of new anticancer therapy using RECIST Version 1.1.

Safety population included participants who received at least 1 dose of any study treatment.

Posted

Count of Participants

Participants

RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

ID	Title	Description
OG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG002

Secondary

Overall Response Rate (ORR)

The ORR was defined as the percentage of participants with a BOR characterized as either a CR or PR relative to the total number of evaluable participants using RECIST Version 1.1. Evaluable participants were defined as treated participants with measurable disease at baseline.

Safety population included participants who received at least 1 dose of any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

ID	Title	Description
OG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.

Secondary

Disease Control Rate (DCR)

The DCR was defined as percentage of participants with CR or PR or SD or Non-PD/Non-CR, per RECIST Version 1.1 relative to total number of treated participants with measurable disease at baseline.

Safety population included participants who received at least 1 dose of any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

At Week 16

ID	Title	Description
OG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG002	Dose Exploration: Cohort -2B	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 85 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.

Secondary

Median Overall Survival (OS)

The OS was the time from date of first study treatment to the date of death from any cause. Participant survival data were collected from all available sources. The OS was calculated using Kaplan-Meier technique.

Safety population included participants who received at least 1 dose of any study treatment.

Posted

Median

95% Confidence Interval

months

RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

ID	Title	Description
OG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG002	Dose Exploration: Cohort -2B

Secondary

Median Duration of Response (DoR)

The DoR was defined as the time from the first date of response (CR or PR) to first date of documented radiographical PD, per investigator using RECIST Version 1.1. This only applied to participants with CR or PR. If a participant was given a new anticancer therapy prior to first response, DoR was not calculated. The DoR was calculated using Kaplan-Meier technique.

Safety population included participants who received at least 1 dose of any study treatment. Only participants with DoR events were analyzed for this outcome measure.

Posted

Median

95% Confidence Interval

months

RECIST assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, EoT visit, then every 2 months thereafter (maximum of 278 weeks).

ID	Title	Description
OG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
OG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dose Exploration: Cohort 1	Participants received irinotecan liposome injection 70 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	5	7	6	7	7	7
EG001	Dose Exploration: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	7	7	2	7	7	7
EG002	Dose Exploration: Cohort -2B	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 85 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	8	10	7	10	10	10
EG003	Dose Exploration: Cohort -3	Participants received irinotecan liposome injection 55 mg/m^2 followed by oxaliplatin 70 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	7	7	4	7	7	7
EG004	Dose Expansion: Cohort -1	Participants received irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2 followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.	17	25	15	25	25	25

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected7 at risk EG0011 events1 affected7 at risk EG0021 events1 affected10 at risk EG0031 events1 affected7 at risk EG0042 events1 affected25 at risk
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0022 events2 affected10 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Small Intestinal Obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Duodenal Ulcer	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Intestinal Obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Large Intestinal Obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Malignant Gastrointestinal Obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Oesophageal Varices Haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Upper Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Anaemia of Malignant Disease	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Bacterial Sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Clostridium Difficile Colitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Neutropenic Sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Disease Progression	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Bile Duct Obstruction	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Biliary Dilatation	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Deep Vein Thrombosis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Orthostatic Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Acute Kidney Injury	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Arteriospasm Coronary	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Subdural Haematoma	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0009 events5 affected7 at risk EG0017 events6 affected7 at risk EG00219 events9 affected10 at risk EG0036 events5 affected7 at risk EG00449 events23 affected25 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00018 events6 affected7 at risk EG00122 events5 affected7 at risk EG00214 events6 affected10 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00012 events5 affected7 at risk EG0017 events4 affected7 at risk EG0028 events5 affected10 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected7 at risk EG0019 events4 affected7 at risk EG0025 events4 affected10 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0005 events2 affected7 at risk EG0015 events3 affected7 at risk EG0023 events3 affected10 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0027 events2 affected10 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected7 at risk EG0012 events2 affected7 at risk EG0022 events2 affected10 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0004 events2 affected7 at risk EG0011 events1 affected7 at risk EG0021 events1 affected10 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0015 events4 affected7 at risk EG0022 events2 affected10 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected7 at risk EG0011 events1 affected7 at risk EG0021 events1 affected10 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0013 events2 affected7 at risk EG0020 events0 affected10 at risk EG003
Pancreatic failure	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0013 events3 affected7 at risk EG0020 events0 affected10 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0023 events2 affected10 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Anal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0013 events2 affected7 at risk EG0020 events0 affected10 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0012 events2 affected7 at risk EG0020 events0 affected10 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0024 events2 affected10 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Abdominal rigidity	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Anal incontinence	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Anal inflammation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Angular cheilitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0022 events1 affected10 at risk EG003
Duodenal ulcer	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0022 events1 affected10 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Epigastric discomfort	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Eructation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Faeces discoloured	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Gastrointestinal oedema	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Large intestinal obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Malignant gastrointestinal obstruction	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Oesophageal ulcer	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Oesophagitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Steatorrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Tongue discolouration	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Varices oesophageal	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0009 events5 affected7 at risk EG00110 events5 affected7 at risk EG00213 events7 affected10 at risk EG003
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected7 at risk EG0011 events1 affected7 at risk EG0022 events2 affected10 at risk EG003
Asthenia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Oedema peripheral	General disorders	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected7 at risk EG0012 events2 affected7 at risk EG0023 events1 affected10 at risk EG003
Chills	General disorders	MedDRA 23.0	Systematic Assessment	EG0003 events2 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Mucosal inflammation	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Malaise	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0012 events2 affected7 at risk EG0020 events0 affected10 at risk EG003
Temperature intolerance	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Axillary pain	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Catheter site erythema	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Catheter site extravasation	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Catheter site haemorrhage	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Catheter site pain	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Cyst	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Disease progression	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Localised oedema	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG00010 events5 affected7 at risk EG0019 events6 affected7 at risk EG0028 events4 affected10 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0005 events4 affected7 at risk EG0013 events2 affected7 at risk EG0026 events5 affected10 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0005 events4 affected7 at risk EG0013 events3 affected7 at risk EG0024 events3 affected10 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0004 events3 affected7 at risk EG0010 events0 affected7 at risk EG0023 events2 affected10 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0004 events2 affected7 at risk EG0010 events0 affected7 at risk EG0023 events2 affected10 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0022 events2 affected10 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0005 events2 affected7 at risk EG0012 events2 affected7 at risk EG0026 events3 affected10 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0016 events3 affected7 at risk EG0023 events2 affected10 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected7 at risk EG0012 events2 affected7 at risk EG0022 events2 affected10 at risk EG003
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected7 at risk EG0011 events1 affected7 at risk EG0021 events1 affected10 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected7 at risk EG0011 events1 affected7 at risk EG0025 events3 affected10 at risk EG003
Taste disorder	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Lethargy	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Neurotoxicity	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Cognitive disorder	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Hyperaesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Lhermitte's sign	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Memory impairment	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Syncope	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0004 events2 affected7 at risk EG00113 events3 affected7 at risk EG0026 events5 affected10 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG00110 events2 affected7 at risk EG0024 events4 affected10 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected7 at risk EG0011 events1 affected7 at risk EG0025 events3 affected10 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0022 events1 affected10 at risk EG003
Neutrophilia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Anaemia of malignant disease	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Cytopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Splenic infarction	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Splenic vein thrombosis	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Weight decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected7 at risk EG0013 events2 affected7 at risk EG0026 events4 affected10 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0022 events2 affected10 at risk EG003
Platelet count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected7 at risk EG0012 events1 affected7 at risk EG0022 events1 affected10 at risk EG003
White blood cell count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected7 at risk EG0022 events2 affected10 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0027 events1 affected10 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Alanine aminotransferase	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Blood creatinine increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Blood magnesium decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Cardiac murmur	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Liver function test increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Lung diffusion test decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Urine output decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected7 at risk EG0010 events0 affected7 at risk EG0023 events2 affected10 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0026 events2 affected10 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0021 events1 affected10 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0013 events2 affected7 at risk EG0020 events0 affected10 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Catarrh	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Depression	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0016 events5 affected7 at risk EG0021 events1 affected10 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Hallucination	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Irritability	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0012 events1 affected7 at risk EG0021 events1 affected10 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0022 events2 affected10 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Bacterial sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Candida infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Fungal infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Gingivitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Helicobacter infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Neutropenic infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Neutropenic sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Paronychia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Sepsis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Septic shock	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Tooth infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Vulvovaginitis trichomonal	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0012 events1 affected7 at risk EG0021 events1 affected10 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0013 events3 affected7 at risk EG0020 events0 affected10 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0021 events1 affected10 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Nail ridging	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Prurigo	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0005 events2 affected7 at risk EG0018 events4 affected7 at risk EG0020 events0 affected10 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0023 events2 affected10 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0003 events2 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Embolism	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Vascular occlusion	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0004 events1 affected7 at risk EG0011 events1 affected7 at risk EG0021 events1 affected10 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Animal scratch	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Oliguria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Ureterolithiasis	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Bile duct obstruction	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Biliary dilatation	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Arteriospasm coronary	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0021 events1 affected10 at risk EG003
Palpitations	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Eye disorder	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Eyelid oedema	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Vision blurred	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected7 at risk EG0020 events0 affected10 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003
Vulvovaginal swelling	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected7 at risk EG0020 events0 affected10 at risk EG003

The comparative Part 2 was removed in a protocol amendment, dated 11 April 2018, before it was initiated, as this comparative part of the study is being undertaken as a stand-alone Phase 3 study D-US-60010-001.

Certain Agreements

ID	Term
D010190	Pancreatic Neoplasms

Ancestor Terms

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004701	Endocrine Gland Neoplasms
D004066	Digestive System Diseases
D010182	Pancreatic Diseases
D004700	Endocrine System Diseases

ID	Term
C584112	irinotecan sucrosofate
D005472	Fluorouracil
D002955	Leucovorin
D000077150	Oxaliplatin

Ancestor Terms

ID	Term
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D056831	Coordination Complexes
D009930	Organic Chemicals

EG0043 events3 affected25 at risk

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EG0043 events3 affected25 at risk

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EG0041 events1 affected25 at risk

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EG0041 events1 affected25 at risk

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EG0043 events1 affected25 at risk

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EG0041 events1 affected25 at risk

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EG0041 events1 affected25 at risk

EG0042 events1 affected25 at risk

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EG0041 events1 affected25 at risk

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EG0041 events1 affected25 at risk

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EG0041 events1 affected25 at risk

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EG0041 events1 affected25 at risk

EG0040 events0 affected25 at risk

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EG00454 events22 affected25 at risk

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EG0049 events7 affected25 at risk

EG0043 events3 affected25 at risk

EG0041 events1 affected25 at risk

EG0042 events2 affected25 at risk

EG0041 events1 affected25 at risk

EG0046 events4 affected25 at risk

EG0040 events0 affected25 at risk

EG0042 events1 affected25 at risk

EG0042 events2 affected25 at risk

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EG0041 events1 affected25 at risk

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EG0041 events1 affected25 at risk

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EG00421 events16 affected25 at risk

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EG0042 events2 affected25 at risk

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EG0041 events1 affected25 at risk

EG00415 events12 affected25 at risk

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EG0047 events5 affected25 at risk

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EG0043 events2 affected25 at risk

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EG0041 events1 affected25 at risk

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EG0044 events3 affected25 at risk

EG0043 events3 affected25 at risk

EG0041 events1 affected25 at risk

EG0042 events2 affected25 at risk

EG0040 events0 affected25 at risk