Vandetanib Gemcitabine Or Placebo Plus Gemcitabine Or Van... | NCT00753675

ID	Type	Description	Link
EUDRACT n° 2007-003056-12

Label	Type	Description	Intervention Names
A	Experimental	Vandetanib 300 mg as a once daily oral dose, from Day 1	Drug: ZD6474, Vandetanib
B	Experimental	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)	Drug: ZD6474, Vandetanib Drug: Gemcitabine
C	Placebo Comparator	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).	Drug: Gemcitabine Drug: Placebo matching ZD6474

Name	Type	Description	Arm Group Labels	Other Names
ZD6474, Vandetanib	Drug	300 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first	A

Measure	Description	Time Frame
Progression Free Survival	Progression was defined as Time from the date of first dose of study medication to progression of disease, or death (it also includes patients who are lost to follow-up or have withdrawn consent) and evaluated with RECIST criteria as an increase of at least 20% in the sum of longest diameter (LD) of target lesion(s) taking as reference the smallest sum of LD since the treatment started or any new lesion(s).	up to 1032 days

Measure	Description	Time Frame
Objective Tumor Response Rate (CR+PR),	Objective Tumor Response Rate was defined as complete response (CR) + partial response (PR) evaluated by RECIST. CR was defined as disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of longest diameters (LD) of target lesion(s) taking as reference the baseline sum of LD	up to 1032 days

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Brescia	BS		Italy
Research Site

PubMed Identifier	Type	Citation	Retractions
12183421	Background	Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Chester R, Jackson JA, Boffey SJ, Valentine PJ, Curwen JO, Musgrove HL, Graham GA, Hughes GD, Thomas AP, Stokes ES, Curry B, Richmond GH, Wadsworth PF, Bigley AL, Hennequin LF. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. 2002 Aug 15;62(16):4645-55.
25538178

ID	Title	Description
FG000	Arm A Vandetanib 300 mg	Vandetanib 300 mg as a once daily oral dose, from Day 1
FG001	Arm B Vandetanib 100mg + Gemcitab	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)

ID	Title	Description
BG000	Arm A Vandetanib 300 mg	Vandetanib 300 mg as a once daily oral dose, from Day 1
BG001	Arm B Vandetanib 100mg + Gemcitab	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
BG002	ARM C Placebo+ Gemcitabine	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00059 BG00158 BG00256 BG003173

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

Progression Free Survival

Progression was defined as Time from the date of first dose of study medication to progression of disease, or death (it also includes patients who are lost to follow-up or have withdrawn consent) and evaluated with RECIST criteria as an increase of at least 20% in the sum of longest diameter (LD) of target lesion(s) taking as reference the smallest sum of LD since the treatment started or any new lesion(s).

ITT

Posted

Median

95% Confidence Interval

days

up to 1032 days

ID	Title	Description
OG000	Arm A Vandetanib 300 mg	Vandetanib 300 mg as a once daily oral dose, from Day 1
OG001	Arm B Vandetanib 100mg + Gemcitab	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
OG002	ARM C Placebo+ Gemcitabine	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).

Units	Counts
Participants	OG00056 OG00157 OG00252

Title

Denominators

Categories

Title	Measurements
	OG000105(72 to 155) OG001114(91 to 193) OG002148(72 to 225)

Secondary

Objective Tumor Response Rate (CR+PR),

Objective Tumor Response Rate was defined as complete response (CR) + partial response (PR) evaluated by RECIST. CR was defined as disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of longest diameters (LD) of target lesion(s) taking as reference the baseline sum of LD

ITT

Posted

Number

Participants

up to 1032 days

ID	Title	Description
OG000	Arm A Vandetanib 300 mg	Vandetanib 300 mg as a once daily oral dose, from Day 1
OG001	Arm B Vandetanib 100mg + Gemcitab	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
OG002	ARM C Placebo+ Gemcitabine	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).

Secondary

Disease Control Rate (CR+PR+SD)

DCR is the sum of patients with a best overall CR, PR or SD (>=8 weeks) by the patient in the analysis

ITT

Posted

Number

Partecipants

up to 1032 days

ID	Title	Description
OG000	Arm A Vandetanib 300 mg	Vandetanib 300 mg as a once daily oral dose, from Day 1
OG001	Arm B Vandetanib 100mg + Gemcitab	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
OG002	ARM C Placebo+ Gemcitabine	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).

Secondary

Duration of Response (DOR)

DOR is defined from the date of first documentation of response until date of PD or death

ITT (best response of CR or PR only)

Posted

Median

95% Confidence Interval

Days

up to 1032 days

ID	Title	Description
OG000	Arm A Vandetanib 300 mg	Vandetanib 300 mg as a once daily oral dose, from Day 1
OG001	Arm B Vandetanib 100mg + Gemcitab	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
OG002	ARM C Placebo+ Gemcitabine	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).

Secondary

Overall Survival

OS is defined from the date of randomization to death

ITT

Posted

Median

95% Confidence Interval

Days

up to 1032 days

ID	Title	Description
OG000	Arm A Vandetanib 300 mg	Vandetanib 300 mg as a once daily oral dose, from Day 1
OG001	Arm B Vandetanib 100mg + Gemcitab	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
OG002	ARM C Placebo+ Gemcitabine	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment		EG0004 events1 affected59 at risk EG00120 events10 affected58 at risk EG00218 events7 affected56 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Abdominal Distension	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0023 events2 affected56 at risk
Asthenia	General disorders	MedDRA 15.0	Systematic Assessment	General disorders and administration site conditions	EG0007 events7 affected59 at risk EG00117 events14 affected58 at risk EG00220 events15 affected56 at risk
Acute Hepatic Failure	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Bacterial Rhinitis	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Alanine aminotransferase	Investigations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0025 events5 affected56 at risk
Agitated Depression	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Anxiety	Psychiatric disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Bladder hypertrophy	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0022 events2 affected56 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Deep Vein thrombosis	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Anemia macrocytic	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Autoimmune thrombocytopenia	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Dessemintaed Intracascula Coagulation	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Hyperbilirubineamia	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0012 events1 affected58 at risk EG0020 events0 affected56 at risk
Iron deficency anemia	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Leukcytosis	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Leukopenia	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0016 events3 affected58 at risk EG00217 events6 affected56 at risk
Pancytopenia	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Platelet production decreased	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0017 events5 affected58 at risk EG0022 events2 affected56 at risk
Thrombocytosis	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
White blood cell disorder	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Neutropenia	Blood and lymphatic system disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG00115 events7 affected58 at risk EG00228 events10 affected56 at risk
Arrhytmia	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0002 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Atrial Fibrillation	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0012 events1 affected58 at risk EG0021 events1 affected56 at risk
Bundle branch block	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Bundle Branch block right	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Cardiac Failure	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Cardiac Failure Acute	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Extrasystoles	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Oedema peripheral	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0012 events2 affected58 at risk EG0020 events0 affected56 at risk
Sinus tachycardia	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Tachycardia	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Torsade de pointes	Cardiac disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Diabete Mellitus	Endocrine disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Hyperglycamia	Endocrine disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Conjunctival hemorrhage	Eye disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Eye pruritus	Eye disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Ocular icterus	Eye disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Periorbital Oedema	Eye disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Abdominal mass	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Abdominal pain	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG00016 events15 affected59 at risk EG0019 events8 affected58 at risk EG00217 events14 affected56 at risk
Abdominal Pain upper	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0003 events3 affected59 at risk EG0016 events6 affected58 at risk EG0026 events6 affected56 at risk
Aborectal discomfort	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Ascites	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0004 events4 affected59 at risk EG0012 events2 affected58 at risk EG0023 events2 affected56 at risk
Constipation	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0013 events3 affected58 at risk EG0029 events9 affected56 at risk
Diarrhoea	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG00032 events15 affected59 at risk EG00113 events6 affected58 at risk EG00210 events8 affected56 at risk
Dry mouth	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Duodenal obstruction	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Dysgeusia	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Dyspepsia	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0024 events2 affected56 at risk
Dyshagia	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0002 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Gastrointestinal toxicity	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Gingivitis	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Haemorrhoids	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Hiccups	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Intestinal Obstruction	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Nausea	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0006 events5 affected59 at risk EG0017 events6 affected58 at risk EG00229 events17 affected56 at risk
Oral Mucosal erythema	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Pelvic Pain	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
proctalgia	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Proctitis	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Stomatitis	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0023 events3 affected56 at risk
Vomiting	Gastrointestinal disorders	MeDRA 15.0	Systematic Assessment		EG00011 events8 affected59 at risk EG0017 events5 affected58 at risk EG00221 events9 affected56 at risk
Chest Pain	General disorders	MeDRA 15.0	Systematic Assessment		EG0003 events3 affected59 at risk EG0012 events2 affected58 at risk EG0022 events1 affected56 at risk
Chills	General disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0012 events1 affected58 at risk EG0020 events0 affected56 at risk
Condition aggravated	General disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0012 events2 affected58 at risk EG0022 events2 affected56 at risk
Fatigue	General disorders	MeDRA 15.0	Systematic Assessment		EG0009 events8 affected59 at risk EG0019 events7 affected58 at risk EG00211 events8 affected56 at risk
General physical health deterioration	General disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Gravitational oedema	General disorders	MeDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Hyperhidrosis	General disorders	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Hyperpyrexia	General disorders	MeDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk EG0022 events2 affected56 at risk
Malaise	General disorders	MeDra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Mucosal Inflammation	General disorders	MeDra 15.0	Systematic Assessment		EG0004 events4 affected59 at risk EG0016 events4 affected58 at risk EG0020 events0 affected56 at risk
Multi organ failure	General disorders	MeDra 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Oedema	General disorders	MeDra 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0023 events3 affected56 at risk
Oedema Peripheral	General disorders	MeDra 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0019 events3 affected58 at risk EG0023 events1 affected56 at risk
Pain	General disorders	MedDra 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0014 events3 affected58 at risk EG0022 events1 affected56 at risk
Pyrexia	General disorders	MedDra 15.0	Systematic Assessment		EG00010 events8 affected59 at risk EG00122 events14 affected58 at risk EG00222 events14 affected56 at risk
Ascites	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Bile Duct Obstruction	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Cholangites	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0003 events3 affected59 at risk EG0013 events2 affected58 at risk EG0023 events3 affected56 at risk
Hepatic Failure	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG00010 events4 affected59 at risk EG00110 events5 affected58 at risk EG0023 events3 affected56 at risk
Hypertrasaminasaemia	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0003 events2 affected59 at risk EG0012 events2 affected58 at risk EG0022 events2 affected56 at risk
Hypoalbuminaemia	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Jaundice	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0003 events2 affected59 at risk EG0013 events3 affected58 at risk EG0023 events3 affected56 at risk
Liver injury	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Dermatitis allergic	Immune system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Seasonal allergy	Immune system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Cystis escherichia	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Folliculitis	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Hepatobiliary infection	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Influenza	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Oral Herpes	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Skin Infection	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Tooth abcess	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0023 events2 affected56 at risk
Urinary tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Viral infection	Infections and infestations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Spinal Fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Alanine aminotransferase increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0012 events2 affected58 at risk EG0021 events1 affected56 at risk
Aspartate aminotranferase	Investigations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Asparteate amonotranferase increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Blood alkaline phosphatase	Investigations	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Blood Bilirubin	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Blood Bilirubin increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0005 events3 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Blood creatine	Investigations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Blood creatinine increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Blood glucose decreased	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Blood lactate dehdrogenase increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Blood potassium increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Blood urea increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0012 events2 affected58 at risk EG0021 events1 affected56 at risk
Electrocardiogram T wave inversion	Investigations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Electrocardiogram abnormal	Investigations	MedDRA 15.0	Systematic Assessment		EG0003 events2 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Electrocardiogram repolarisation abnormaly	Investigations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Gamma -glumayltransferase	Investigations	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0012 events1 affected58 at risk EG0025 events3 affected56 at risk
International normalised ratio increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Platelet count decreased	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0013 events3 affected58 at risk EG0020 events0 affected56 at risk
Platelet count increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Transaminase increased	Investigations	MedDRA 15.0	Systematic Assessment		EG0002 events1 affected59 at risk EG0012 events1 affected58 at risk EG0020 events0 affected56 at risk
Weight decreased	Investigations	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0005 events5 affected59 at risk EG00110 events8 affected58 at risk EG0024 events4 affected56 at risk
Deydratation	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Hyperbilirubinaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Hypercalcemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Hypercreatininaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0012 events2 affected58 at risk EG0021 events1 affected56 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Metabolic Acidosis	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0012 events2 affected58 at risk EG0020 events0 affected56 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0011 events1 affected58 at risk EG0023 events3 affected56 at risk
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0022 events2 affected56 at risk
Hypercreatinaemia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0022 events2 affected56 at risk
Neck Pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Pain in the extremity	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Spinal Compression Fracture	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Clonus	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Convulsion	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Dizziness	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0012 events2 affected58 at risk EG0020 events0 affected56 at risk
Dysarthria	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Dysgeusia	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Epilepsy	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Head Discomfort	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0025 events5 affected56 at risk
Hypogeusia	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Insomnia	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Loss of consciousness	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Neuralgia	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Paraesthesia	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0003 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0013 events2 affected58 at risk EG0020 events0 affected56 at risk
Somnolence	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Syncope	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0003 events2 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Tremor	Nervous system disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Depression	Psychiatric disorders	Medra 15.0	Systematic Assessment		EG0002 events1 affected59 at risk EG0013 events2 affected58 at risk EG0022 events2 affected56 at risk
Insomnia	Psychiatric disorders	Medra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Panic disorder	Psychiatric disorders	Medra 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Sleep disorder due to general medical condition , insomnia type	Psychiatric disorders	Medra 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Dysuria	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0015 events3 affected58 at risk EG0020 events0 affected56 at risk
Haematuria	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Hypercreatininaemia	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Oliguria	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Proteinuria	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0013 events3 affected58 at risk EG0025 events1 affected56 at risk
Renal failure	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0014 events3 affected58 at risk EG0021 events1 affected56 at risk
Renal failure acute	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Strangury	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Urinary incontinence	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Urinary Tract Infection	Renal and urinary disorders	Medra 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Dysponea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment		EG0003 events3 affected59 at risk EG0013 events3 affected58 at risk EG0024 events4 affected56 at risk
Dysponea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0012 events2 affected58 at risk EG0020 events0 affected56 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0012 events2 affected58 at risk EG0020 events0 affected56 at risk
Vertigo	Ear and labyrinth disorders	MeDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Metastic Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedRa 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Metastic Pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedRa 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Tumor associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedRa 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0008 events2 affected59 at risk EG0014 events3 affected58 at risk EG0020 events0 affected56 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Drug Eruption	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk EG0022 events2 affected56 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG00013 events5 affected59 at risk EG0014 events4 affected58 at risk EG0025 events4 affected56 at risk
Exfoliative rash	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Face Oedema	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Folliculitis	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0004 events3 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Onycholysis	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0012 events2 affected58 at risk EG0025 events4 affected56 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0022 events1 affected56 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG00021 events15 affected59 at risk EG0015 events5 affected58 at risk EG0023 events3 affected56 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Skin Toxicity	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment		EG0006 events2 affected59 at risk EG0013 events3 affected58 at risk EG0021 events1 affected56 at risk
Diastolic hypotension	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Epistaxis	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Essential hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Haemorrhoids	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG00017 events14 affected59 at risk EG00110 events9 affected58 at risk EG0026 events4 affected56 at risk
Hypertensive crisis	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Hypotension	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0002 events2 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Phlebitis	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0022 events1 affected56 at risk
Pulmonary embolism	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Systolic hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Venous insufficiency	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Venous thrombosis	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Hepatic pain	Hepatobiliary disorders	MeDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Contrast media allergy	Immune system disorders	MedDRA 15.0	Systematic Assessment		EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Urine colour abnormal	Investigations	MeDRA 15.0	Systematic Assessment		EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk

ID	Term
D001661	Biliary Tract Neoplasms
D005706	Gallbladder Neoplasms
D018281	Cholangiocarcinoma

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D001660	Biliary Tract Diseases
D004066	Digestive System Diseases
D005705	Gallbladder Diseases
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A Vandetanib 300 mg	Vandetanib 300 mg as a once daily oral dose, from Day 1	16	59	57	59
EG001	Arm B Vandetanib 100mg + Gemcitab	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)	15	58	53	58
EG002	ARM C Placebo+ Gemcitabine	Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).	12	56	50	56

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Disseminated Intravascular	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Abdominal Pain	Gastrointestinal disorders		Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Asthenia	General disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Acute Hepatic Failure	Hepatobiliary disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Pneumonia	Infections and infestations	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Blood Bilirubin	Investigations	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Cachexia	Metabolism and nutrition disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Epilepsy	Nervous system disorders	MeDRA 15.0	Systematic Assessment	EG0002 events2 affected59 at risk EG0010 events0 affected0 at risk EG0020 events0 affected0 at risk
Oliguria	Renal and urinary disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0012 events2 affected58 at risk EG0020 events0 affected56 at risk
Hypertension	Vascular disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Pancytopenia	Blood and lymphatic system disorders	MeDra	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MeDra	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Cardiac Failure Acute	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Torsade de Pointes	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Ascites	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Duodenal Obstruction	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Intestinal Obstruction	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0003 events3 affected59 at risk EG0010 events0 affected58 at risk EG0022 events2 affected56 at risk
Condition Aggravated	General disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Fatigue	General disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
General Physical Health Deterioration	General disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Pyrexia	General disorders	MeDRA 15.0	Systematic Assessment	EG0003 events3 affected59 at risk EG0010 events0 affected58 at risk EG0022 events2 affected56 at risk
Cholangites	Hepatobiliary disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0011 events1 affected58 at risk EG0021 events1 affected56 at risk
Hepatic Failure	Hepatobiliary disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Hyperbilirubineamia	Hepatobiliary disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Jaundice	Hepatobiliary disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0012 events2 affected58 at risk EG0022 events2 affected56 at risk
Blood Bilirubin increased	Investigations	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Electrocardiogram Repolarisation Abnormaly	Investigations	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Dehydration	Metabolism and nutrition disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Metabolic Acidosis	Metabolism and nutrition disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Renal Failure	Renal and urinary disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0012 events2 affected58 at risk EG0021 events1 affected56 at risk
Renal Failure Acute	Renal and urinary disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0011 events1 affected58 at risk EG0020 events0 affected56 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0021 events1 affected56 at risk
Pulmonary Hypertension	Respiratory, thoracic and mediastinal disorders	MeDRA 15.0	Systematic Assessment	EG0000 events0 affected59 at risk EG0012 events2 affected58 at risk EG0020 events0 affected56 at risk
Hypotension	Vascular disorders	MeDRA 15.0	Systematic Assessment	EG0001 events1 affected59 at risk EG0010 events0 affected58 at risk EG0020 events0 affected56 at risk