Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Comb... | NCT03713593

NCT03713593

ID	Type	Description
MK-7902-002	Other Identifier	MSD Protocol Number
E7080-G000-311	Other Identifier	Eisai Protocol Number
LEAP-002	Other Identifier	MSD
194590	Registry Identifier	JAPIC-CTI
2018-002983-26	EudraCT Number

Status Module

Name	Class
Eisai Inc.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
lenvatinib plus pembrolizumab	Experimental	Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.	Drug: lenvatinib Biological: pembrolizumab
lenvatinib plus placebo	Active Comparator	Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.	Drug: lenvatinib Drug: saline placebo

Name	Type	Description	Arm Group Labels	Other Names
lenvatinib	Drug	Administered orally once a day	lenvatinib plus pembrolizumab lenvatinib plus placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS was defined as the time from the date of the first documentation of disease progression, as determined by blinded independent central review (BICR) per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.	Up to approximately 41 months
Overall Survival (OS)	OS was defined as the time from randomization until death from any cause	Up to approximately 41 months

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Is male or female and ≥18 years of age at the time of signing the informed consent
Has a diagnosis of hepatocellular carcinoma confirmed by radiology, histology, or cytology
Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
Has a Child-Pugh class A liver score
Has a predicted life expectancy of >3 months
Has at least one measurable hepatocellular carcinoma (HCC) lesion based on RECIST 1.1 as confirmed by BICR
Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
Participants with hepatitis B will be eligible as long as their virus is well controlled

Exclusion Criteria:

Has had esophageal or gastric variceal bleeding within the last 6 months
Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula
Has clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study intervention
Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability
Has had major surgery to the liver within 4 weeks prior to the first dose of study intervention
Has had a minor surgery (ie, simple excision) within 7 days prior to the first dose of study intervention
Has serious non-healing wound, ulcer, or bone fracture
Has received any systemic chemotherapy for HCC or chemotherapy for any malignancy in the past 3 years
Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, or CD137)
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that has undergone potentially curative therapy
Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator
Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of their excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has urine protein ≥1 grams/24 hours
Prolongation of corrected QT (QTc) interval to >480 milliseconds (corrected by Fridericia Formula)
Has left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
Has an active infection requiring systemic therapy with the exceptions of hepatitis B virus (HBV) or hepatitis C virus (HCV)
Has a known history of human immunodeficiency virus (HIV) infection
Has known active tuberculosis (Bacillus tuberculosis)
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
Has had an allogenic tissue/solid organ transplant

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
The University of Arizona Cancer Center - North Campus ( Site 0621)		Tucson	Arizona	85721	United States

PubMed Identifier	Type	Citation	Retractions
38039993	Result	Llovet JM, Kudo M, Merle P, Meyer T, Qin S, Ikeda M, Xu R, Edeline J, Ryoo BY, Ren Z, Masi G, Kwiatkowski M, Lim HY, Kim JH, Breder V, Kumada H, Cheng AL, Galle PR, Kaneko S, Wang A, Mody K, Dutcus C, Dubrovsky L, Siegel AB, Finn RS; LEAP-002 Investigators. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1399-1410. doi: 10.1016/S1470-2045(23)00469-2.

Label	URL
Merck Clinical Trials Information	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 7, 2023

Arm/Group Information

ID	Title	Description
BG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
BG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00064.2± 10.9 BG00164.1± 12.1 BG00264.1± 11.5

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00078 BG00172 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00048 BG00141 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG00013 BG0018 BG002

Eastern Cooperative Oncology Group (ECOG) Performance Status

Randomization of participants in the study was stratified by an ECOG Performance Status of 0 (Fully active, able to carry on all pre-disease performance without restriction) or 1 (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature) or 2 (Ambulatory but unable to work). The number of participants with missing ECOG performance status is indicated for each treatment arm.

Count of Participants

Participants

Title

Denominators

Categories

ECOG = 0

Title	Measurements
	BG000267 BG001

Geographic Region

Randomization of participants in this study was stratified by geographic region of the enrolling site (Asia without Japan versus Japan and Western regions).

Count of Participants

Participants

Title

Denominators

Categories

Asia without Japan

Title	Measurements
	BG000121 BG001123

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 (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

PFS was defined as the time from the date of the first documentation of disease progression, as determined by blinded independent central review (BICR) per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Units	Counts
Participants	OG000395 OG001399

Title

Denominators

Categories

Title	Measurements
	OG0008.2(6.3 to 8.3) OG0018.1(6.3 to 8.3)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Hazard Ratio (HR)	0.834			2-Sided	95	0.712	0.978			Based on Cox model with Efron's method of tie handling with treatment as a covariate stratified by geographic region, MPVI or extrahepatic spread or both, AFP and ECOG PS.		Other	Descriptive assessment

Primary

Overall Survival (OS)

OS was defined as the time from randomization until death from any cause

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Units

Secondary

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

DOR was determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR, per RECIST 1.1 as assessed by BICR, until the first documented disease progression or death due to any cause, whichever occurred first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

The analysis population consisted of all randomized participants. Participants were analyzed based on the population of responders (participants that achieved complete or partial response).

Posted

Median

Full Range

Months

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

DCR was defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per RECIST 1.1 as assessed by BICR. SD must be achieved at ≥6 weeks after randomization to be considered best overall response. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Time to Disease Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by BICR. RECIST 1.1 was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

PFS was defined as the time from the first dose of study intervention to the first documented progressive disease (PD) per mRECIST by BICR or death due to any cause, whichever occurred first. mRECIST for HCC allowed evaluation of treatment effects that were not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the sum of diameters (SODs) of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

ORR wass defined as the percentage of participants who have a confirmed complete response (CR: disappearance of any intratumoral arterial enhancement in all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of viable [enhancement in the arterial phase] target lesions, taking as reference the baseline sum of the diameters of target lesions) per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo

Secondary

Duration of Response (DOR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

DOR was determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR, per mRECIST as assessed by BICR, until the first documented disease progression or death due to any cause, whichever occurs first. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.

The analysis population consisted of all participants who received at least 1 dose of study treatment. Participants were analyzed based on the population of responders (participants that achieved complete or partial response).

Posted

Median

Full Range

Months

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Disease Control Rate (DCR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

DCR was defined as the percentage of participants who have a best overall response of CR, PR, or SD per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. SD must be achieved at ≥6 weeks after randomization to be considered best overall response. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Time to Disease Progression (TTP) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

TTP was defined as the time from randomization to the first documented disease progression per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Number of Participants Who Experienced an Adverse Event (AE)

Number of participants who experienced an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment

The analysis population consisted of all randomized participants who received at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Up to approximately 68 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Number of Participants Who Experienced an Serious Adverse Event (SAE)

Number of participants who experienced a SAE defined as an AE that resulted in death, was life threatening, resulting in persistent or significant disability or incapacity, resulting in or prolonged a hospitalization, was a congenital anomaly or birth defect, was a cancer, was associated with an overdose, or was another important medical event

The analysis population consisted of all randomized participants who received at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Up to approximately 68 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Number of Participants Who Experienced an Immune-related Adverse Event (irAE) of Clinical Interest

Number of participants who experienced an AE representing an immunologic etiology and considered to be causally related to drug exposure

The analysis population consisted of all randomized participants who received at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Up to approximately 41 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Number of Participants Who Experienced an Hepatic Event of Clinical Interest (HECI)

Number of participants who experienced a hepatic ECI not due to disease progression as judged by the investigator.

The analysis population consisted of all randomized participants. Participants were analyzed in the treatment group to which they were randomized.

Posted

Count of Participants

Participants

Up to approximately 68 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Secondary

Number of Participants Who Discontinued Study Drug Due to an Adverse Event

Number of participants who discontinued study treatment due to an AE

The analysis population consisted of all randomized participants who received at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Up to approximately 68 months

ID	Title	Description
OG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.
OG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lenvatinib + Pembrolizumab	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.	314	395	185	395	390	395
EG001	Lenvatinib + Placebo	Participants received lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo was administered for up to 35 cycles (approximately 24 months). Lenvatinib was administered until progressive disease or unacceptable toxicity.	352	399	159	395	388	395

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected395 at risk EG0011 events1 affected395 at risk
Immune thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0012 events2 affected395 at risk
Angina pectoris	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected395 at risk EG0010 events0 affected395 at risk
Angina unstable	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Atrioventricular block	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Cardiac arrest	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Cardiac failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events2 affected395 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Coronary artery disease	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0012 events2 affected395 at risk
Myocardial injury	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Myocarditis	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Hypophysitis	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Thyroiditis	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Cataract	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Diabetic retinopathy	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Glaucoma	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Pterygium	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Abdominal hernia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0008 events8 affected395 at risk EG0014 events4 affected395 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Anal fistula	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Ascites	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected395 at risk EG00110 events10 affected395 at risk
Colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00013 events13 affected395 at risk EG0015 events5 affected395 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Duodenal ulcer perforation, obstructive	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected395 at risk EG0010 events0 affected395 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Enteritis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Gastric varices haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Gastritis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0012 events2 affected395 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Haemoperitoneum	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events2 affected395 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0011 events1 affected395 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Ileus	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events2 affected395 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Mechanical ileus	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Melaena	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Mesenteric vein thrombosis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Oesophageal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Oesophageal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0015 events5 affected395 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events2 affected395 at risk
Pneumatosis intestinalis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Proctitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Small intestinal perforation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Subileus	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0015 events4 affected395 at risk
Varices oesophageal	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected395 at risk EG0010 events0 affected395 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0010 events0 affected395 at risk
Death	General disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected395 at risk EG0013 events3 affected395 at risk
Drowning	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0012 events2 affected395 at risk
General physical health deterioration	General disorders	MedDRA 27.0	Systematic Assessment	EG0008 events7 affected395 at risk EG0010 events0 affected395 at risk
Hyperthermia malignant	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected395 at risk EG0010 events0 affected395 at risk
Mucosal inflammation	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Oedema	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0012 events2 affected395 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0015 events4 affected395 at risk
Stent-graft endoleak	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Biliary obstruction	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events2 affected395 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0016 events2 affected395 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0005 events4 affected395 at risk EG0018 events8 affected395 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0013 events3 affected395 at risk
Hepatic haemorrhage	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Hepatic necrosis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Hepatic pain	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Hepatorenal syndrome	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected395 at risk EG0012 events2 affected395 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Liver injury	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Abdominal infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Abdominal sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Anal abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Anorectal infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Appendicitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Appendicitis perforated	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0013 events3 affected395 at risk
Biliary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0013 events2 affected395 at risk
Bronchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0013 events3 affected395 at risk
COVID-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected395 at risk EG0013 events3 affected395 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0011 events1 affected395 at risk
Cellulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0012 events2 affected395 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Cryptococcosis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Cystitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Cytomegalovirus colitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Encephalitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Endocarditis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Fungaemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Large intestine infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Liver abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Osteomyelitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Periodontitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Peritonitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected395 at risk EG0012 events2 affected395 at risk
Peritonitis bacterial	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Pleurisy bacterial	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0008 events8 affected395 at risk EG0017 events7 affected395 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Pneumonia cryptococcal	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Pneumonia klebsiella	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Postoperative wound infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Prostatic abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0012 events2 affected395 at risk
Salmonellosis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0005 events3 affected395 at risk EG0012 events2 affected395 at risk
Septic shock	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0013 events3 affected395 at risk
Spinal cord infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Streptococcal sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0005 events4 affected395 at risk EG0012 events2 affected395 at risk
Urosepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Viral infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected395 at risk EG0011 events1 affected395 at risk
Amylase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0011 events1 affected395 at risk
Blood bilirubin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected395 at risk EG0011 events1 affected395 at risk
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Blood glucose decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Blood thyroid stimulating hormone decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
False positive investigation result	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Platelet count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0012 events2 affected395 at risk
Troponin T increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0013 events3 affected395 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0014 events4 affected395 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Hypervolaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0004 events3 affected395 at risk EG0010 events0 affected395 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0011 events1 affected395 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0012 events2 affected395 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events1 affected395 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Fistula	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Osteolysis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events2 affected395 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events2 affected395 at risk
Tenosynovitis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Liver carcinoma ruptured	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Malignant neoplasm of unknown primary site	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Skin squamous cell carcinoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0012 events2 affected395 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Cerebral infarction	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0010 events0 affected395 at risk
Embolic stroke	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00027 events21 affected395 at risk EG00112 events11 affected395 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0011 events1 affected395 at risk
Myasthenia gravis	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Ruptured cerebral aneurysm	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Seizure	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Transient global amnesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Completed suicide	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Confusional state	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0012 events1 affected395 at risk
Delirium	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0012 events2 affected395 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Nephritis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Nephrotic syndrome	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Prerenal failure	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk
Renal colic	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Renal failure	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Renal infarct	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Renal tubular necrosis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected395 at risk EG0010 events0 affected395 at risk
Scrotal inflammation	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Chronic respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected395 at risk EG0010 events0 affected395 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events1 affected395 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0013 events2 affected395 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Idiopathic pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Lower respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events1 affected395 at risk EG0010 events0 affected395 at risk
Oropharyngeal spasm	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Henoch-Schonlein purpura	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Hidradenitis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Lichenoid keratosis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Parapsoriasis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Pemphigoid	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected395 at risk EG0010 events0 affected395 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0010 events0 affected395 at risk
Aortic aneurysm	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected395 at risk EG0012 events2 affected395 at risk
Hypertensive crisis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0012 events2 affected395 at risk
Hypertensive emergency	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected395 at risk EG0010 events0 affected395 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected395 at risk EG0011 events1 affected395 at risk
Vasculitis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected395 at risk EG0011 events1 affected395 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG00061 events51 affected395 at risk EG00188 events64 affected395 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG00054 events19 affected395 at risk EG00138 events22 affected395 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG00032 events31 affected395 at risk EG00116 events15 affected395 at risk
Hypothyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG000207 events167 affected395 at risk EG001202 events159 affected395 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00033 events27 affected395 at risk EG00120 events18 affected395 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00088 events74 affected395 at risk EG00191 events74 affected395 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00052 events46 affected395 at risk EG00153 events40 affected395 at risk
Ascites	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00035 events28 affected395 at risk EG00134 events29 affected395 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00081 events67 affected395 at risk EG00181 events73 affected395 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000359 events187 affected395 at risk EG001352 events167 affected395 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00020 events20 affected395 at risk EG00114 events14 affected395 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00041 events33 affected395 at risk EG00118 events14 affected395 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000123 events89 affected395 at risk EG001120 events82 affected395 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00055 events41 affected395 at risk EG00147 events35 affected395 at risk
Toothache	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00028 events24 affected395 at risk EG00123 events18 affected395 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00093 events54 affected395 at risk EG00193 events61 affected395 at risk
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG00090 events73 affected395 at risk EG00185 events61 affected395 at risk
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG000148 events126 affected395 at risk EG001124 events98 affected395 at risk
Malaise	General disorders	MedDRA 27.0	Systematic Assessment	EG00024 events20 affected395 at risk EG00135 events30 affected395 at risk
Mucosal inflammation	General disorders	MedDRA 27.0	Systematic Assessment	EG00030 events25 affected395 at risk EG00125 events19 affected395 at risk
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG00086 events63 affected395 at risk EG00168 events54 affected395 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG00060 events48 affected395 at risk EG00166 events45 affected395 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00027 events20 affected395 at risk EG00116 events14 affected395 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00048 events35 affected395 at risk EG00165 events42 affected395 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG000162 events93 affected395 at risk EG001155 events89 affected395 at risk
Amylase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00064 events40 affected395 at risk EG00130 events18 affected395 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG000195 events117 affected395 at risk EG001179 events105 affected395 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00064 events50 affected395 at risk EG00154 events35 affected395 at risk
Blood bilirubin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG000222 events101 affected395 at risk EG001216 events108 affected395 at risk
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00060 events39 affected395 at risk EG00141 events25 affected395 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00078 events65 affected395 at risk EG00172 events56 affected395 at risk
Lipase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00079 events57 affected395 at risk EG00159 events37 affected395 at risk
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG00073 events34 affected395 at risk EG00185 events39 affected395 at risk
Platelet count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG000170 events101 affected395 at risk EG001198 events110 affected395 at risk
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG000139 events121 affected395 at risk EG001105 events90 affected395 at risk
White blood cell count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG00075 events29 affected395 at risk EG001105 events45 affected395 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG000183 events146 affected395 at risk EG001167 events120 affected395 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00033 events24 affected395 at risk EG00146 events25 affected395 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00022 events14 affected395 at risk EG00126 events20 affected395 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00051 events24 affected395 at risk EG00164 events31 affected395 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00085 events62 affected395 at risk EG00199 events61 affected395 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00075 events39 affected395 at risk EG00160 events36 affected395 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00046 events27 affected395 at risk EG00156 events28 affected395 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00069 events43 affected395 at risk EG00164 events39 affected395 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00024 events19 affected395 at risk EG00143 events23 affected395 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG000114 events89 affected395 at risk EG00193 events77 affected395 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00072 events60 affected395 at risk EG00149 events43 affected395 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00027 events25 affected395 at risk EG00115 events14 affected395 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00022 events19 affected395 at risk EG00127 events23 affected395 at risk
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00030 events26 affected395 at risk EG00130 events28 affected395 at risk
Dysgeusia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00026 events22 affected395 at risk EG00121 events19 affected395 at risk
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00067 events51 affected395 at risk EG00158 events43 affected395 at risk
Insomnia	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG00040 events35 affected395 at risk EG00149 events43 affected395 at risk
Haematuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG00043 events27 affected395 at risk EG00155 events24 affected395 at risk
Proteinuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG000280 events136 affected395 at risk EG001268 events153 affected395 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00066 events55 affected395 at risk EG00149 events43 affected395 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00094 events83 affected395 at risk EG00192 events79 affected395 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00047 events44 affected395 at risk EG00132 events24 affected395 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00028 events25 affected395 at risk EG00142 events29 affected395 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00024 events23 affected395 at risk EG00117 events15 affected395 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG000155 events133 affected395 at risk EG001141 events125 affected395 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00079 events67 affected395 at risk EG00157 events44 affected395 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00079 events63 affected395 at risk EG00146 events35 affected395 at risk
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG000248 events180 affected395 at risk EG001258 events200 affected395 at risk

ID	Term
D006528	Carcinoma, Hepatocellular
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008113	Liver Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004066	Digestive System Diseases
D008107	Liver Diseases