Nivolumab (BMS-936558; MDX-1106) in Combination With Suni... | NCT01472081

Name	Class
Ono Pharmaceutical Co., Ltd.	INDUSTRY

Label	Type	Description	Intervention Names
Arm S: Nivolumab + Sunitinib	Experimental	Nivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons Sunitinib 50 mg capsule by mouth on Days 1-28 of 42 day cycle until Progressive disease (PD), toxicity or discontinue for other reasons	Biological: Nivolumab Drug: Sunitinib
Arm P: Nivolumab + Pazopanib	Experimental	Nivolumab 0.3, 2.0 (starting dose), 5.0 mg/kg solution intravenously every 21 days until Progressive disease (PD), toxicity or discontinue for other reasons Pazopanib 800 mg tablet by mouth daily until Progressive disease (PD), toxicity or discontinue for other reasons	Biological: Nivolumab Biological: Pazopanib
Arm I-1: Nivolumab + Ipilimumab	Experimental	Nivolumab 3 mg/kg solution intravenously (IV) every 21 days during Induction phase and every 14 days during Maintenance phase until Progressive disease (PD), toxicity or discontinue for other reasons Ipilimumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase (Ipilimumab will not be administered during Maintenance phase) until Progressive disease (PD), toxicity or discontinue for other reasons	Biological: Nivolumab Biological: Ipilimumab
Arm I-3: Nivolumab + Ipilimumab	Experimental	Nivolumab 1mg/kg solution intravenously (IV) every 21 days during Induction phase and 3mg/kg solution intravenously (IV) every 14 days during Maintenance phase Ipilimumab 3mg/kg solution intravenously (IV) every 21 days during Induction phase. Ipilimumab will not be administered during Maintenance phase

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab	Biological		Arm I-1: Nivolumab + Ipilimumab Arm I-3: Nivolumab + Ipilimumab Arm IN-3: Nivolumab+Ipilimumab Arm P: Nivolumab + Pazopanib Arm S: Nivolumab + Sunitinib

Measure	Description	Time Frame
Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation	Safety assessments by treatment arm and dose level were based on incidence of AEs, and the incidence of serious adverse events (SAEs). AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.	From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)

Measure	Description	Time Frame
Best Overall Response Rate (BOR)	BOR was defined as the best response designation over the study as a whole, recorded between the date of first dose of study medication and the date of objectively documented progression per RECIST 1.1 criteria or the date of subsequent anti-cancer therapy, whichever occurred first. CR = Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
City Of Hope		Duarte	California	91010-3000	United States
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins

PubMed Identifier	Type	Citation	Retractions
30348216	Derived	Amin A, Plimack ER, Ernstoff MS, Lewis LD, Bauer TM, McDermott DF, Carducci M, Kollmannsberger C, Rini BI, Heng DYC, Knox J, Voss MH, Spratlin J, Berghorn E, Yang L, Hammers HJ. Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study. J Immunother Cancer. 2018 Oct 22;6(1):109. doi: 10.1186/s40425-018-0420-0.
24308791

Label	URL
BMS Clinical Trial Information	View source

ID	Title	Description
FG000	Arm S: SUN + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With AEs, SAEs, and AEs Leading to Discontinuation

Safety assessments by treatment arm and dose level were based on incidence of AEs, and the incidence of serious adverse events (SAEs). AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.

All treated participants

Posted

Number

participants

From date of first dose to date of last dose plus 100 days (assessed up to March 2016, approximately 49 months)

ID	Title	Description
OG000	Arm S: SUN + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG001	Arm S: SUN + NIV5	Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG002	Arm P: PAZ + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG003	Arm I-1: IPI1 + NIV3	Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.
OG004	Arm I-3: IPI3 + NIV1	Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.
OG005	Arm IN-3: IPI3 + NIV3	Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.

Units	Counts
Participants	OG0007 OG00126 OG00220 OG003

Title

Denominators

Categories

All-causality SAEs (any grade)

Title	Measurements
	OG0003 OG00116 OG00213 OG003

Secondary

Best Overall Response Rate (BOR)

BOR was defined as the best response designation over the study as a whole, recorded between the date of first dose of study medication and the date of objectively documented progression per RECIST 1.1 criteria or the date of subsequent anti-cancer therapy, whichever occurred first.

CR = Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

All treated participants

Posted

Number

percentage of participants

From date of first dose to date of disease progression or subsequent anti-cancer therapy, whichever occurred first (assessed up to March 2016, approximately 49 months)

ID	Title	Description
OG000	Arm S: SUN + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG001

Secondary

Objective Response Rate (ORR)

ORR was defined as the proportion of participants who achieved a BOR of either complete response (CR) or partial response (PR) in the population of interest.

CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

All treated participants

Posted

Number

95% Confidence Interval

percentage of participants

From date of first dose to interim analysis (Assessed up to March 2016, approximately 49 months)

ID	Title	Description
OG000	Arm S: SUN + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG001	Arm S: SUN + NIV5	Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG002	Arm P: PAZ + NIV2

Secondary

Duration of Response (DOR)

DOR was computed for participants with BOR of CR or PR only, and defined as the time between the date of first documented objective response and the date of the first subsequent disease progression or death. Participants who remained alive and had not progressed were censored on the last tumor assessment date (prior to subsequent cancer therapy).

All treated participants

Posted

Median

95% Confidence Interval

weeks

From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)

ID	Title	Description
OG000	Arm S: SUN + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG001	Arm S: SUN + NIV5	Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG002	Arm P: PAZ + NIV2

Secondary

Rate of Progression-free Survival (PFS) at Week 24

Rate of PFS at week 24 was defined as the proportion of participants remaining progression free or surviving at 24 weeks, calculated by the product-limit method (Kaplan-Meier estimate) which took into account censored data. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.

All treated participants

Posted

Number

95% Confidence Interval

Percentage of participants with PFS

24 weeks

ID	Title	Description
OG000	Arm S: SUN + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG001	Arm S: SUN + NIV5	Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG002	Arm P: PAZ + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Secondary

Progression-free Survival (PFS)

PFS was defined as the time from the date of first dose of study medication to the date of first disease progression or death. Participants who did not have any on-study tumor assessment and did not die were censored on the date of first dose of study medication.

All treated participants

Posted

Median

95% Confidence Interval

months

From date of first dose to date of disease progression or death, whichever occurred first (assessed up to March 2016, approximately 49 months)

ID	Title	Description
OG000	Arm S: SUN + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG001	Arm S: SUN + NIV5	Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
OG002	Arm P: PAZ + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Methaemoglobinaemia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG0030 affected47 at risk EG0040 affected6 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Hypophysitis	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hypopituitarism	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Diplopia	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Autoimmune colitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected20 at risk EG0024 affected47 at risk EG003
Duodenitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Erosive duodenitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Gastritis erosive	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Large intestinal obstruction	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Chills	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Hernia	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Mucosal ulceration	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Pyrexia	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0024 affected47 at risk EG003
Sudden death	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Systemic inflammatory response syndrome	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hepatitis acute	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Appendicitis perforated	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Lung infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0021 affected47 at risk EG003
Pneumonia legionella	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Skin infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Viral infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Blood creatinine increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Lipase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Platelet count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Transaminases increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected20 at risk EG0020 affected47 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Malignant ascites	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0026 affected47 at risk EG003
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Tumour flare	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Balance disorder	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Seizure	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Syncope	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Transient global amnesia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0023 affected47 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Haemorrhage	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hypertension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Thrombosis	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Localised infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected33 at risk EG0013 affected20 at risk EG0027 affected47 at risk EG00310 affected47 at risk EG0041 affected6 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Left ventricular dysfunction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Palpitations	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0026 affected47 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0025 affected47 at risk EG003
Ear congestion	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0020 affected47 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Autoimmune thyroiditis	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Cushingoid	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Endocrine disorder	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0010 affected20 at risk EG0023 affected47 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected33 at risk EG0014 affected20 at risk EG00210 affected47 at risk EG003
Lymphocytic hypophysitis	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Dry eye	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Eye pain	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0010 affected20 at risk EG0023 affected47 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Periorbital oedema	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Photopsia	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Vision blurred	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected20 at risk EG0026 affected47 at risk EG003
Visual impairment	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Vitreous detachment	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Vitreous floaters	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Vitreous haemorrhage	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0014 affected20 at risk EG0024 affected47 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0017 affected20 at risk EG00210 affected47 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0012 affected20 at risk EG0024 affected47 at risk EG003
Anal inflammation	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Autoimmune colitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Breath odour	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0009 affected33 at risk EG0018 affected20 at risk EG00214 affected47 at risk EG003
Defaecation urgency	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00021 affected33 at risk EG00114 affected20 at risk EG00212 affected47 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00011 affected33 at risk EG0012 affected20 at risk EG0025 affected47 at risk EG003
Duodenitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00011 affected33 at risk EG0015 affected20 at risk EG0026 affected47 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0013 affected20 at risk EG0021 affected47 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0006 affected33 at risk EG0011 affected20 at risk EG0025 affected47 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0009 affected33 at risk EG0013 affected20 at risk EG0024 affected47 at risk EG003
Glossodynia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00020 affected33 at risk EG00116 affected20 at risk EG00219 affected47 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0014 affected20 at risk EG0021 affected47 at risk EG003
Paraesthesia oral	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected33 at risk EG0012 affected20 at risk EG0027 affected47 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected20 at risk EG0023 affected47 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected33 at risk EG0019 affected20 at risk EG00215 affected47 at risk EG003
Asthenia	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Chest discomfort	General disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Chest pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0013 affected20 at risk EG0025 affected47 at risk EG003
Chills	General disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected33 at risk EG0016 affected20 at risk EG00213 affected47 at risk EG003
Face oedema	General disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Fatigue	General disorders	MedDRA 18.1	Systematic Assessment	EG00029 affected33 at risk EG00115 affected20 at risk EG00231 affected47 at risk EG003
Generalised oedema	General disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Influenza like illness	General disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Localised oedema	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Malaise	General disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected20 at risk EG0021 affected47 at risk EG003
Mucosal inflammation	General disorders	MedDRA 18.1	Systematic Assessment	EG00011 affected33 at risk EG0015 affected20 at risk EG0022 affected47 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Oedema	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Oedema peripheral	General disorders	MedDRA 18.1	Systematic Assessment	EG00011 affected33 at risk EG0015 affected20 at risk EG00212 affected47 at risk EG003
Pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Pyrexia	General disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected33 at risk EG0017 affected20 at risk EG00218 affected47 at risk EG003
Sensation of foreign body	General disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Temperature intolerance	General disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Bronchitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Ear infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Gingivitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Groin abscess	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Infected bite	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Lung infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0021 affected47 at risk EG003
Post procedural infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Rhinitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Sinusitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0024 affected47 at risk EG003
Skin infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Tinea infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Tooth infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0008 affected33 at risk EG0017 affected20 at risk EG0029 affected47 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Vulvitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0025 affected47 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0023 affected47 at risk EG003
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0013 affected20 at risk EG0020 affected47 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Sunburn	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG00013 affected33 at risk EG0015 affected20 at risk EG0028 affected47 at risk EG003
Amylase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0010 affected20 at risk EG0024 affected47 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG00012 affected33 at risk EG0016 affected20 at risk EG0029 affected47 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0013 affected20 at risk EG0022 affected47 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Blood creatinine increased	Investigations	MedDRA 18.1	Systematic Assessment	EG00012 affected33 at risk EG0012 affected20 at risk EG0027 affected47 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Lipase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG00211 affected47 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0009 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0006 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Platelet count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0006 affected33 at risk EG0010 affected20 at risk EG0023 affected47 at risk EG003
Weight decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0014 affected20 at risk EG0025 affected47 at risk EG003
Weight increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0027 affected47 at risk EG003
White blood cell count decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0007 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG00016 affected33 at risk EG00111 affected20 at risk EG00213 affected47 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0007 affected33 at risk EG0016 affected20 at risk EG0027 affected47 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected20 at risk EG0024 affected47 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected33 at risk EG0014 affected20 at risk EG0027 affected47 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0012 affected20 at risk EG0025 affected47 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0012 affected20 at risk EG0021 affected47 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected20 at risk EG0020 affected47 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0015 affected20 at risk EG0023 affected47 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0009 affected33 at risk EG0011 affected20 at risk EG0026 affected47 at risk EG003
Hypophagia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0012 affected20 at risk EG0023 affected47 at risk EG003
Polydipsia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00012 affected33 at risk EG0019 affected20 at risk EG00224 affected47 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0007 affected33 at risk EG0016 affected20 at risk EG00215 affected47 at risk EG003
Costochondritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0028 affected47 at risk EG003
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Lower extremity mass	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0015 affected20 at risk EG0023 affected47 at risk EG003
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected20 at risk EG0020 affected47 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected20 at risk EG0023 affected47 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0015 affected20 at risk EG0026 affected47 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0014 affected20 at risk EG0023 affected47 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected33 at risk EG0015 affected20 at risk EG00211 affected47 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0012 affected20 at risk EG0028 affected47 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00012 affected33 at risk EG0016 affected20 at risk EG0028 affected47 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Ataxia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Carpal tunnel syndrome	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Cerebellar syndrome	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Cognitive disorder	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG00011 affected33 at risk EG0013 affected20 at risk EG00210 affected47 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG00021 affected33 at risk EG00110 affected20 at risk EG0025 affected47 at risk EG003
Epilepsy	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG00013 affected33 at risk EG0015 affected20 at risk EG00215 affected47 at risk EG003
Hyperaesthesia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0020 affected47 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0012 affected20 at risk EG0021 affected47 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0024 affected47 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Restless legs syndrome	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Sciatica	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Seizure	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Somnolence	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Speech disorder	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Syncope	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Tremor	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0012 affected20 at risk EG0027 affected47 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Depression	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0014 affected20 at risk EG0029 affected47 at risk EG003
Irritability	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Azotaemia	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0021 affected47 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0021 affected47 at risk EG003
Polyuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Breast mass	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Testicular pain	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG00018 affected33 at risk EG00113 affected20 at risk EG00224 affected47 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0015 affected20 at risk EG0027 affected47 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG00012 affected33 at risk EG0014 affected20 at risk EG00213 affected47 at risk EG003
Dyspnoea at rest	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected33 at risk EG0013 affected20 at risk EG0027 affected47 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0006 affected33 at risk EG0012 affected20 at risk EG0020 affected47 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0023 affected47 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected33 at risk EG0011 affected20 at risk EG0029 affected47 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected33 at risk EG0013 affected20 at risk EG0026 affected47 at risk EG003
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0024 affected47 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0022 affected47 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0011 affected20 at risk EG0028 affected47 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0024 affected47 at risk EG003
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0027 affected47 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG00011 affected33 at risk EG0013 affected20 at risk EG00211 affected47 at risk EG003
Dyshidrotic eczema	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Hair colour changes	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0006 affected33 at risk EG0014 affected20 at risk EG0021 affected47 at risk EG003
Hair growth abnormal	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0012 affected20 at risk EG0025 affected47 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG00013 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0009 affected33 at risk EG0019 affected20 at risk EG00218 affected47 at risk EG003
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0009 affected33 at risk EG0017 affected20 at risk EG00218 affected47 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0023 affected47 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG00010 affected33 at risk EG0014 affected20 at risk EG0027 affected47 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0012 affected20 at risk EG0022 affected47 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0022 affected47 at risk EG003
Skin mass	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0023 affected47 at risk EG003
Yellow skin	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0007 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Flushing	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0013 affected20 at risk EG0023 affected47 at risk EG003
Haematoma	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Hot flush	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected33 at risk EG0012 affected20 at risk EG0023 affected47 at risk EG003
Hypertension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG00017 affected33 at risk EG0018 affected20 at risk EG0024 affected47 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0014 affected20 at risk EG0023 affected47 at risk EG003
Orthostatic hypertension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003
Phlebitis	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Autoimmune hypothyroidism	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Retching	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0021 affected47 at risk EG003
Cellulitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Genital infection fungal	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected33 at risk EG0011 affected20 at risk EG0021 affected47 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected33 at risk EG0010 affected20 at risk EG0020 affected47 at risk EG003
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected33 at risk EG0011 affected20 at risk EG0020 affected47 at risk EG003

ID	Term
D002292	Carcinoma, Renal Cell
C538445	Clear-cell metastatic renal cell carcinoma

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D007680	Kidney Neoplasms
D014571	Urologic Neoplasms
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D007674	Kidney Diseases
D014570	Urologic Diseases
D052801	Male Urogenital Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description
BG000	Arm S: SUN + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
BG001	Arm S: SUN + NIV5	Nivolumab 5 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
BG002	Arm P: PAZ + NIV2	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.
BG003	Arm I-1: IPI1 + NIV3	Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.
BG004	Arm I-3: IPI3 + NIV1	Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.
BG005	Arm IN-3: IPI3 + NIV3	Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.
BG006	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SUNITINIB+NIVOLUMAB	Nivolumab (2mg/kg or 5mg/kg)administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Sunitinib 50 mg orally on Day 1 - 28 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.	19	33	33	33
EG001	PAZOPANIB+NIVOLUMAB	Nivolumab 2 mg/kg administered on Day 1 and 22 of each 6 week (42 day) cycle as a 1-hour IV infusion followed 60 minutes later with Pazopanib 800 mg orally on Day 1 - 42 of each 42 day cycle until Progressive Disease (PD), toxicity or discontinuation for other reasons.	13	20	20	20
EG002	NIVO 3+IPI 1 (MG/KG)	Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 1 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.	29	47	47	47
EG003	NIVO 1+IPI 3 (MG/KG)	Induction: Nivolumab 1 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.	30	47	46	47
EG004	NIVO 3+IPI 3 (MG/KG)	Induction: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion followed by Ipilimumab 3 mg/kg administered IV infusion over 90 minutes every 3 weeks for 4 doses. Maintenance: Nivolumab 3 mg/kg was administered as a 1-hour IV infusion every 2 weeks, starting 3 weeks after the 4th dose of induction therapy or after Day 113 if the 4th dose of induction therapy had not been administered due to treatment delays.	4	6	6	6

ID	Term
D000077594	Nivolumab
C516667	pazopanib
D000077210	Sunitinib
D000074324	Ipilimumab