Safety and Efficacy of Selonsertib in Adults With Nonalco... | NCT03053050

NCT03053050

ID	Type	Description	Link
2016-004374-18	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
SEL 18 mg	Experimental	Randomized Phase: Selonsertib (SEL) 18 mg tablet + placebo to match SEL 6 mg tablet for 240 weeks Open-Label (OL) Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.	Drug: SEL Drug: Placebo to match SEL 6 mg
SEL 6 mg	Experimental	Randomized Phase: SEL 6 mg tablet + placebo to match SEL 18 mg tablet for 240 weeks OL Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.	Drug: SEL Drug: Placebo to match SEL 18 mg
Placebo	Placebo Comparator	Randomized Phase: Placebo to match SEL 6 mg tablet + placebo to match SEL 18 mg tablet for 240 weeks OL Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.	Drug: Placebo to match SEL 6 mg Drug: Placebo to match SEL 18 mg

Name	Type	Description	Arm Group Labels	Other Names
SEL	Drug	Tablets administered orally once daily	SEL 18 mg SEL 6 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis According to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) Classification Without Worsening of NASH at Week 48	Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH CRN classification. NASH CRN fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Worsening of NASH was defined as ≥ 1 point increase from baseline in hepatocellular ballooning or lobular inflammation according to the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) criteria. As defined by NAS, hepatocellular ballooning ranges from 0-2 and lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation.	Week 48
Event-Free Survival (EFS) at Week 240 as Assessed by Time to First Clinical Event	EFS was assessed by the time to the first clinical event, including progression to cirrhosis on liver biopsy, liver decompensation events, liver transplantation, and all-cause mortality.	Week 240

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Had Progression to Cirrhosis at Week 48	Progression to cirrhosis was defined as a change in NASH CRN fibrosis stage from < 4 at baseline to 4 at Week 48.	Week 48
Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 240

Eligibility Module

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Institute of Liver Health		Chandler	Arizona	85224	United States
Banner University Medical Center-Phoenix

References Module

Citations

PubMed Identifier	Type	Citation
31271665	Result	Anstee QM, Lawitz EJ, Alkhouri N, Wong VW, Romero-Gomez M, Okanoue T, Trauner M, Kersey K, Li G, Han L, Jia C, Wang L, Chen G, Subramanian GM, Myers RP, Djedjos CS, Kohli A, Bzowej N, Younes Z, Sarin S, Shiffman ML, Harrison SA, Afdhal NH, Goodman Z, Younossi ZM. Noninvasive Tests Accurately Identify Advanced Fibrosis due to NASH: Baseline Data From the STELLAR Trials. Hepatology. 2019 Nov;70(5):1521-1530. doi: 10.1002/hep.30842. Epub 2019 Aug 19.
	Result	Alkhouri N, Younossi ZM, Lawitz EJ, Wong VWS, Romero-Gomez M, et al. Impact of age on routinely available noninvasive tests for the discrimination of advanced fibrosis due to NASH in the phase 3 STELLAR trials of the ASK1 inhibitor selonsertib [Poster SAT-273]. European Association for the Study of the Liver (EASL); 2019; Vienna Austria.
30779990

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks.
FG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks.

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	Yes	No	No	Study Protocol	May 31, 2018	Apr 29, 2020

Arm/Group Information

ID	Title	Description
BG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
BG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
BG002	Placebo	Randomized Phase: Placebo to match SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
BG003	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
	BG00057± 9.1 BG00157± 9.2 BG00257± 9.0 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000181 BG001196 BG002

Race/Ethnicity, Customized

Not Permitted = Local regulators did not allow collection of race or ethnicity information.

Count of Participants

Participants

Title

Denominators

Categories

Race

Title	Measurements
American Indian or Alaska Native	BG0005 BG0011

Race/Ethnicity, Customized

Not Permitted = Local regulators did not allow collection of race or ethnicity information.

Count of Participants

Participants

Title

Denominators

Categories

Ethnicity

Title	Measurements
Not Hispanic or Latino	BG000269 BG001269

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000161 BG001172 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis According to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) Classification Without Worsening of NASH at Week 48

Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH CRN classification. NASH CRN fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Worsening of NASH was defined as ≥ 1 point increase from baseline in hepatocellular ballooning or lobular inflammation according to the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) criteria. As defined by NAS, hepatocellular ballooning ranges from 0-2 and lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation.

The Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG002	Placebo	Randomized Phase: Placebo to match SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.

Units	Counts
Participants	OG000322 OG001321 OG002159

Title

Denominators

Categories

Title	Measurements
	OG0009.6(6.6 to 13.4) OG00112.1(8.8 to 16.2) OG00213.2(8.4 to 19.5)

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 OG002		Mantel Haenszel		0.4941	Difference between SEL 18 mg and Placebo, 95% confidence interval (CI) and p-value were obtained by stratum-adjusted Mantel-Haenszel method with baseline diabetes mellitus status and Enhanced Liver Fibrosis (ELF) test score as stratification factors.	Percentage Difference	-2.1			2-Sided	95	-8.3	4.0					Superiority
OG001

Primary

Event-Free Survival (EFS) at Week 240 as Assessed by Time to First Clinical Event

EFS was assessed by the time to the first clinical event, including progression to cirrhosis on liver biopsy, liver decompensation events, liver transplantation, and all-cause mortality.

No data was analyzed as the study was terminated and no participants reached the Week 240 timepoint.

Posted

Week 240

ID	Title	Description
OG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.

Secondary

Percentage of Participants Who Had Progression to Cirrhosis at Week 48

Progression to cirrhosis was defined as a change in NASH CRN fibrosis stage from < 4 at baseline to 4 at Week 48.

Participants in the Full Analysis Set were analyzed.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG002

Secondary

Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 240

Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH CRN classification. NASH CRN fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Worsening of NASH was defined as ≥ 1 point increase from baseline in hepatocellular ballooning or lobular inflammation according to the NAS criteria. As defined by NAS, hepatocellular ballooning ranges from 0-2 and lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation.

No data was analyzed as the study was terminated and no participants reached the Week 240 timepoint.

Posted

Week 240

ID	Title	Description
OG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.

Secondary

Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis at Week 48

Participants in the Full Analysis Set were analyzed.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.

Secondary

Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis at Week 240

No data was analyzed as the study was terminated and no participants reached the Week 240 timepoint.

Posted

Week 240

ID	Title	Description
OG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.

Secondary

Percentage of Participants Who Had NASH Resolution Without Worsening of Fibrosis at Week 48

NASH resolution was defined as lobular inflammation of 0 or 1 from ≥ 1 at baseline and hepatocellular ballooning of 1 from a value ≥ 1 at baseline; both criteria were necessary conditions. Evaluable participants had baseline lobular inflammation and hepatocellular ballooning ≥ 1. Worsening of Fibrosis was defined by an increase in Fibrosis stage from 3 to 4 as defined by NASH CRN.

Participants in the Full Analysis Set with available data were analyzed.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.

Secondary

Percentage of Participants Who Had NASH Resolution Without Worsening of Fibrosis at Week 240

No data was analyzed as the study was terminated and no participants reached the Week 240 timepoint.

Posted

Week 240

ID	Title	Description
OG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.
OG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks OL Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SEL 18 mg	Randomized Phase: Selonsertib (SEL) 18 mg tablet orally once daily + placebo to match SEL 6 mg tablet orally once daily for 240 weeks.	322	47	322	248	322
EG001	SEL 6 mg	Randomized Phase: SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks.	321	36	321	254	321
EG002	Placebo	Randomized Phase: Placebo to match SEL 6 mg tablet orally once daily + placebo to match SEL 18 mg tablet orally once daily for 240 weeks.	159	17	159	130	159
EG003	Open-Label SEL 18 mg	Open-Label (OL) Phase: Participants who experienced a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, were offered the option to roll over into an OL phase to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the randomized phase.	99	6	99	48	99

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0012 affected321 at risk EG0020 affected159 at risk EG0030 affected99 at risk
Haemorrhagic anaemia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Cardiovascular disorder	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Left ventricular dysfunction	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Retinal detachment	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Diverticulum	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Internal hernia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0021 affected159 at risk EG003
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Pancreatitis relapsing	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Varices oesophageal	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Chest pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Hepatic haemorrhage	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Hepatic lesion	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Bronchitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Campylobacter gastroenteritis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Cellulitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Cellulitis of male external genital organ	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Escherichia urinary tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Otitis externa	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0003 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Postoperative abscess	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Sepsis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0012 affected321 at risk EG0022 affected159 at risk EG003
Sinusitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Urosepsis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0012 affected321 at risk EG0020 affected159 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Pancreatic leak	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Patella fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Ammonia increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Blood glucose increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Body temperature increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Oxygen saturation decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0021 affected159 at risk EG003
Breast cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Carcinoid tumour pulmonary	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Haemangioma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Metastatic lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Squamous cell carcinoma of the vulva	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Ataxia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Hepatic encephalopathy	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Sciatica	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Seizure	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Syncope	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Toxic encephalopathy	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Bipolar I disorder	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0021 affected159 at risk EG003
Schizoaffective disorder	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Cystitis interstitial	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Ureterolithiasis	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Prostatitis	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Testicular necrosis	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0021 affected159 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Hepatic hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected322 at risk EG0011 affected321 at risk EG0020 affected159 at risk EG003
Peripheral artery thrombosis	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected322 at risk EG0010 affected321 at risk EG0020 affected159 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00013 affected322 at risk EG00112 affected321 at risk EG0028 affected159 at risk EG0032 affected99 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00022 affected322 at risk EG00127 affected321 at risk EG00215 affected159 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00033 affected322 at risk EG00126 affected321 at risk EG00216 affected159 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00040 affected322 at risk EG00143 affected321 at risk EG00219 affected159 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00052 affected322 at risk EG00147 affected321 at risk EG00230 affected159 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00032 affected322 at risk EG00139 affected321 at risk EG00214 affected159 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00019 affected322 at risk EG00118 affected321 at risk EG0028 affected159 at risk EG003
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG00035 affected322 at risk EG00133 affected321 at risk EG00212 affected159 at risk EG003
Oedema peripheral	General disorders	MedDRA 21.1	Systematic Assessment	EG00018 affected322 at risk EG0019 affected321 at risk EG0024 affected159 at risk EG003
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG00042 affected322 at risk EG00150 affected321 at risk EG00225 affected159 at risk EG003
Bronchitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00023 affected322 at risk EG00121 affected321 at risk EG0026 affected159 at risk EG003
Influenza	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00019 affected322 at risk EG00120 affected321 at risk EG00214 affected159 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00046 affected322 at risk EG00140 affected321 at risk EG00221 affected159 at risk EG003
Sinusitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00021 affected322 at risk EG00121 affected321 at risk EG00212 affected159 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00041 affected322 at risk EG00146 affected321 at risk EG00221 affected159 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00014 affected322 at risk EG00127 affected321 at risk EG00213 affected159 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG00010 affected322 at risk EG0015 affected321 at risk EG0028 affected159 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00033 affected322 at risk EG00130 affected321 at risk EG00218 affected159 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00033 affected322 at risk EG00127 affected321 at risk EG00211 affected159 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00016 affected322 at risk EG00117 affected321 at risk EG0027 affected159 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00014 affected322 at risk EG00118 affected321 at risk EG0028 affected159 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG00020 affected322 at risk EG00115 affected321 at risk EG00211 affected159 at risk EG003
Dizziness	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG00016 affected322 at risk EG00130 affected321 at risk EG0022 affected159 at risk EG003
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG00036 affected322 at risk EG00138 affected321 at risk EG00218 affected159 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG00028 affected322 at risk EG00118 affected321 at risk EG00214 affected159 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00023 affected322 at risk EG00120 affected321 at risk EG00211 affected159 at risk EG003

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases