Study to Evaluate the Efficacy and Safety of Selonsertib... | NCT04026165

ID	Type	Description	Link
JapicCTI-194911	Registry Identifier	Japan Pharmaceutical Information Center
2018-003951-39	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Selonsertib	Experimental	Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive SEL 18 mg for at least 48 weeks.	Drug: SEL Drug: Placebo
Placebo	Placebo Comparator	Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks. Randomized Period: Participants will be randomized to receive placebo-to-match SEL for at least 48 weeks.	Drug: SEL Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
SEL	Drug	Tablet administered orally once daily	Placebo Selonsertib

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr)	The values of eGFRcr were calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation (2009). eGFRcr = 141min(Standardized Serum Creatinine (Scr)/kappa, 1) ^alphamax(Scr/ kappa, 1)^(-1.209)0.993^Age1.018[if female]*1.159[if Black], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment-specific Baselines = the average of Visits A and B values for Placebo, and the average of Visit C and Day 1 values for SEL. Visit A= enrollment, Visit B= 7-14 days after Visit A, Visit C= 21-28 days after Visit B, and Visit 1= 7-14 days after Visit C.	Treatment-specific Baselines (From enrollment (Visit A) up to 14 days after Visit A for placebo and from Visit C up to 14 days after Visit C for SEL)
eGFRcr Slope	The values of eGFRcr were calculated using the CKD-EPI Creatinine Equation (2009). eGFRcr = 141min(Scr/kappa, 1) ^alphamax(Scr/kappa, 1)^(-1.209)0.993^Age1.018[if female]*1.159[if Black], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment specific baselines for eGFRcr: average of Visit A (enrollment) and Visit B (7-14 days after Visit A) values for Placebo, and average of Visit C (21-28 days after Visit B, and Visit 1 (7-14 days after Visit C) values for SEL.	Treatment-specific Baselines through Week 84

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Kidney Clinical Events at Week 48	Kidney clinical events were defined as any of the following events: confirmed ≥ 40% decline in eGFRcr from baseline, or kidney failure (dialysis performed for at least 4 weeks, kidney transplantation, or confirmed decrease in eGFRcr to < 15 mL/min/1.73 m^2 for participants without dialysis or kidney transplantation), or death due to kidney disease.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Diagnosis of type 2 diabetes mellitus (T2DM) as per local guidelines.
Estimated glomerular filtration rate (eGFR) value calculated by central laboratory utilizing samples collected during screening and prior to enrollment of ≥ 20 mL/min/1.73 m^2 to < 60 mL/min/1.73 m^2 with albuminuria
- eGFR and urine albumin to creatinine ratio (UACR) must meet criteria a, b, or c
  - a: eGFR (mL/min/1.73 m^2): ≥ 45 to < 60; UACR (mg/g): ≥ 600 to 5000
  - b: eGFR (mL/min/1.73 m^2): ≥ 30 to < 45; UACR (mg/g): ≥ 300 to 5000
  - c: eGFR (mL/min/1.73 m^2): ≥ 20 to < 30; UACR (mg/g): ≥ 150 to 5000
Treatment with either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)
- Individuals not receiving an ACEi or ARB may be enrolled if there is documented intolerance to ACEi and ARB
- Individuals receiving less-than-maximal dose of an ACEi or ARB may be enrolled if there is a documented reason that the maximum labeled dose of ACEi and ARB could not be reached
Individuals already receiving sodium-glucose co-transporter-2 (SGLT-2) inhibitors must be on a stable dose for at least 2 weeks prior to enrollment
Mean systolic blood pressure (SBP) must be <160 mmHg and mean diastolic blood pressure (DBP) must be <100 mmHg
Required baseline laboratory data, analyzed by central laboratory, within 30 days prior to enrollment

Key Exclusion Criteria:

Hemoglobin A1c (HbA1c) > 12.0% within 30 days prior to enrollment
Individuals with diagnosis of type 1 diabetes mellitus (T1DM) or maturity onset diabetes of the young (MODY)
Body mass index (BMI) > 50 kg/m^2
UACR > 5000 mg/g on any measurement during screening
End stage kidney disease (ESKD) (i.e., chronic hemodialysis, chronic peritoneal dialysis, or history of kidney transplantation)
Anticipated progression to ESKD (need for chronic hemodialysis, chronic peritoneal dialysis or receipt of kidney transplant) within 3 months after enrollment
Unstable cardiovascular disease
Pregnant or lactating females or planning to become pregnant or breastfeed during the study
Concurrent use of either
1. ACEi and ARB or
2. Mineralocorticoid receptor antagonist (MRA) or direct renin inhibitor (DRI) in combination with an ACEi or ARB for at least 2 weeks prior to Enrollment
Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the individual or impair the assessment of study results

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Kidney Disease and Hypertension Centers		Glendale	Arizona	85306	United States
AKDHC Medical Research Services, LLC

PubMed Identifier	Type	Citation	Retractions
39018154	Derived	Heerspink HJL, Perkovic V, Tuttle KR, Pergola PE, Mahaffey KW, Patel UD, Ishida JH, Kuo A, Chen F, Kustra R, Petrovic V, Rossing P, Kashihara N, Chertow GM. Selonsertib in Patients with Diabetic Kidney Disease: A Phase 2b Randomized Active Run-In Clinical Trial. J Am Soc Nephrol. 2024 Dec 1;35(12):1726-1736. doi: 10.1681/ASN.0000000000000444. Epub 2024 Jul 17.

Label	URL
Gilead Clinical Trials Website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Run-in Placebo	Participants received placebo to match selonsertib (SEL) tablet orally once daily for at least one week.
FG001	Run-in SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 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	Apr 13, 2020	Jul 19, 2022

Arm/Group Information

ID	Title	Description
BG000	Run-in SEL 18 mg, Not Randomized	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period and were not randomized.
BG001	Randomized SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received SEL 18 mg tablet orally once daily for at least 48 weeks.
BG002	Randomized Placebo	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received placebo-to-match SEL tablet orally once daily for at least 48 weeks.
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
	BG00065± 9.7 BG00165± 9.3 BG00266± 8.8 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00012 BG00148 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00039 BG001132 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Race

Title	Measurements
American Indian or Alaska Native	BG0000 BG0012 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

New Zealand

Title	Measurements
	BG0000 BG0017 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

Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr)

The values of eGFRcr were calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation (2009). eGFRcr = 141*min(Standardized Serum Creatinine (Scr)/kappa, 1) ^alpha*max(Scr/ kappa, 1)^(-1.209)*0.993^Age*1.018[if female]*1.159[if Black], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years.

Treatment-specific Baselines = the average of Visits A and B values for Placebo, and the average of Visit C and Day 1 values for SEL.

Visit A= enrollment, Visit B= 7-14 days after Visit A, Visit C= 21-28 days after Visit B, and Visit 1= 7-14 days after Visit C.

The Full Analysis Set included all participants who were randomized in the study, and received at least one dose of study drug in the Randomization Phase.

Posted

Mean

Standard Deviation

mL/min/1.73m^2

Treatment-specific Baselines (From enrollment (Visit A) up to 14 days after Visit A for placebo and from Visit C up to 14 days after Visit C for SEL)

ID	Title	Description
OG000	Randomized SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received SEL 18 mg tablet orally once daily for at least 48 weeks.
OG001	Randomized Placebo	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received placebo-to-match SEL tablet orally once daily for at least 48 weeks.

Units	Counts
Participants	OG000154 OG001156

Title

Denominators

Categories

Title	Measurements
	OG00032.7± 10.59 OG00134.9± 10.81

Primary

eGFRcr Slope

The values of eGFRcr were calculated using the CKD-EPI Creatinine Equation (2009). eGFRcr = 141*min(Scr/kappa, 1) ^alpha*max(Scr/kappa, 1)^(-1.209)*0.993^Age*1.018[if female]*1.159[if Black], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment specific baselines for eGFRcr: average of Visit A (enrollment) and Visit B (7-14 days after Visit A) values for Placebo, and average of Visit C (21-28 days after Visit B, and Visit 1 (7-14 days after Visit C) values for SEL.

Participants in the Full Analysis Set (included all participants who were randomized in the study and received at least 1 dose of study drug in the randomization phase) with available data were analyzed.

Posted

Least Squares Mean

Standard Error

mL/min/1.73m^2/year

Treatment-specific Baselines through Week 84

ID	Title	Description
OG000	Randomized SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received SEL 18 mg tablet orally once daily for at least 48 weeks.
OG001	Randomized Placebo	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received placebo-to-match SEL tablet orally once daily for at least 48 weeks.

Secondary

Percentage of Participants With Kidney Clinical Events at Week 48

Participants in the Full Analysis Set were analyzed.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	Randomized SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received SEL 18 mg tablet orally once daily for at least 48 weeks.
OG001	Randomized Placebo	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received placebo-to-match SEL tablet orally once daily for at least 48 weeks.

Units	Counts
Participants

Secondary

Time From Randomization to First Occurrence of a Kidney Clinical Event: Event Rate Per 100 Participant-years for First Occurrence of Kidney Clinical Event

Kidney clinical events were defined as any of the following events: confirmed ≥ 40% decline in eGFRcr from baseline, or kidney failure (dialysis performed for at least 4 weeks, kidney transplantation, or confirmed decrease in eGFRcr to < 15 mL/min/1.73 m^2 for participants without dialysis or kidney transplantation), or death due to kidney disease. This outcome measure was analyzed using event rate per 100 participant-years for first occurrence of kidney clinical event. Participant year was calculated as total follow-up duration across all participants in a given group. Follow-up duration was defined as time from Randomization to the earliest of study completion, premature study discontinuation, death, or event of interest in each row.

Participants in the Full Analysis Set were analyzed.

Posted

Number

events per 100 participant-years

From randomization up to Week 101

ID	Title	Description
OG000	Randomized SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received SEL 18 mg tablet orally once daily for at least 48 weeks.
OG001	Randomized Placebo	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received placebo-to-match SEL tablet orally once daily for at least 48 weeks.

Secondary

Pre-run-in Baseline Estimated Glomerular Filtration Rate Based on Cystatin C (eGFRcys)

eGFRcys = Estimated Glomerular Filtration Rate calculated by CKD-EPI Cystatin C Equation (2012). eGFR = 133*min(Standardized Serum Cystatin (Scys)/0.8, 1) ^(-0.499)*max(Scys/0.8, 1)^(-1.328)*0.996^Age*0.932[if female]. min indicates the minimum of Scys/0.8 or 1, max indicates the maximum of Scr/0.8 or 1, and age is in years.

Participants in the Full Analysis Set were analyzed.

Posted

Mean

Standard Deviation

mL/min/1.73m^2

Pre-run-in Baseline (Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values)

ID	Title	Description
OG000	Randomized SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received SEL 18 mg tablet orally once daily for at least 48 weeks.
OG001	Randomized Placebo	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received placebo-to-match SEL tablet orally once daily for at least 48 weeks.

Units	Counts

Secondary

eGFRcys Slope

eGFRcys = Estimated Glomerular Filtration Rate calculated by CKD-EPI Cystatin C Equation (2012). eGFR = 133*min(Scys/0.8, 1) ^(-0.499)*max(Scys/0.8, 1)^(-1.328)*0.996^Age*0.932[if female]. min indicates the minimum of Scys/0.8 or 1, max indicates the maximum of Scr/0.8 or 1, and age is in years. Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values.

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

Posted

Least Squares Mean

Standard Error

mL/min/1.73m^2/year

Pre-run-in Baseline through Week 84

ID	Title	Description
OG000	Randomized SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received SEL 18 mg tablet orally once daily for at least 48 weeks.
OG001	Randomized Placebo	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks in the Run-in period, were then randomized, and received placebo-to-match SEL tablet orally once daily for at least 48 weeks.

Units	Counts
Participants

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	Run-in Placebo	Participants received placebo-to-match SEL tablet orally once daily for at least one week.	0	384	0	0	0	0
EG001	Run-in SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 4 weeks.	1	357	16	357	37	357
EG002	Randomized SEL 18 mg	Participants received SEL 18 mg tablet orally once daily for at least 48 weeks after Randomization.	5	154	45	154	55	154
EG003	Randomized Placebo	Participants received placebo-to-match SEL tablet orally once daily for at least 48 weeks after Randomization.	7	156	45	156	49	156

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG0030 affected156 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Nephrogenic anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Acute left ventricular failure	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0022 affected154 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Atrioventricular block complete	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0021 affected154 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0021 affected154 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0013 affected357 at risk EG0023 affected154 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Cardiogenic shock	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Cardiopulmonary failure	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0022 affected154 at risk EG003
Hypertensive heart disease	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Pulseless electrical activity	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Sinus node dysfunction	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Ventricular fibrillation	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Arteriovenous malformation	Congenital, familial and genetic disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Retinopathy hypertensive	Eye disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Colitis ischaemic	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0021 affected154 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Large intestine polyp	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Generalised oedema	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Impaired healing	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Hepatic mass	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Bronchitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Bursitis infective	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Cellulitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Covid-19	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0025 affected154 at risk EG003
Covid-19 pneumonia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Cystitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Escherichia bacteraemia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Gangrene	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Influenza	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Large intestine infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0021 affected154 at risk EG003
Otitis externa	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Pneumonia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0025 affected154 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Scrotal abscess	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Septic shock	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Soft tissue infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Urosepsis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Wound infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0022 affected154 at risk EG003
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Arteriogram coronary abnormal	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Carbon dioxide abnormal	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Electrocardiogram abnormal	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
International normalised ratio increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Transaminases increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0021 affected154 at risk EG003
Hypervolaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0023 affected154 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0023 affected154 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Iron deficiency	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0022 affected154 at risk EG003
Hepatic cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Cerebral haemorrhage	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Hemiparesis	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Syncope	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0022 affected154 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Device end of service	Product Issues	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0013 affected357 at risk EG00210 affected154 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Diabetic nephropathy	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
End stage renal disease	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Nephropathy	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Renal mass	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Subcapsular renal haematoma	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Urethral stenosis	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0020 affected154 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0012 affected357 at risk EG0020 affected154 at risk EG003
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0021 affected154 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0021 affected154 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0022 affected154 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Blood pressure inadequately controlled	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Hypertension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Hypotension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0020 affected154 at risk EG003
Peripheral artery occlusion	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0010 affected357 at risk EG0021 affected154 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG0025 affected154 at risk EG0038 affected156 at risk
Constipation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0017 affected357 at risk EG00211 affected154 at risk EG003
Oedema peripheral	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0015 affected357 at risk EG00211 affected154 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0016 affected357 at risk EG0025 affected154 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0018 affected357 at risk EG00212 affected154 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0014 affected357 at risk EG0026 affected154 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG0011 affected357 at risk EG00210 affected154 at risk EG003
Hypertension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected0 at risk EG00110 affected357 at risk EG00211 affected154 at risk EG003

ID	Term
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D048909	Diabetes Complications
D003920	Diabetes Mellitus
D004700	Endocrine System Diseases