A Study to Evaluate Safety and Effects of Sotagliflozin 4... | NCT03242018

NCT03242018

ID	Type	Description	Link
2016-004906-32
U1111-1190-7589	Other Identifier	UTN

Status Module

Name	Class
Sanofi	INDUSTRY

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 milligrams [mg] in appearance) orally once daily for up to 56 weeks.	Drug: Placebo
Sotagliflozin 200 mg	Experimental	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 56 weeks.	Drug: Placebo Drug: Sotagliflozin
Sotagliflozin 400 mg	Experimental	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56 weeks.	Drug: Sotagliflozin

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.	Placebo Sotagliflozin 200 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline to Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo	An ANCOVA model was used for the analysis.	Baseline to Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

Other Outcomes

Measure	Description	Time Frame
Percentage of Participants With Hypoglycemic Events	Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia [typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L)]; Severe [an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions] or documented symptomatic hypoglycemia [typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL].

Eligibility Module

Name	Affiliation	Role
Suman Wason, MD	Lexicon Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 8405033		Guntersville	Alabama	35976-2206	United States
Investigational Site Number 8405005

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38770818	Derived	Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.
34338408

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
FG001	Sotagliflozin 200 mg

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	Dec 15, 2017	Apr 13, 2021

Arm/Group Information

ID	Title	Description
BG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
BG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
BG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 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
	BG00068.0± 8.3 BG00166.8± 10.0 BG00267.3± 9.6 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00051 BG00148 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00041 BG00133 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0007 BG0018 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Argentina

Title	Measurements
	BG0007 BG0013 BG002

Hemoglobin A1c (HbA1c)

Mean

Standard Deviation

percentage of HbA1c

Title

Denominators

Categories

Title	Measurements
	BG0008.38± 1.06 BG0018.28± 1.03 BG002

Systolic Blood Pressure (SBP)

Mean

Standard Deviation

millimeter of mercury (mmHg)

Title

Denominators

Categories

Title	Measurements
	BG000144.72± 15.56 BG001143.10± 14.98 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

Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo

An analysis of covariance (ANCOVA) model was used for the analysis.

Intent-to-treat (ITT) population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts & washout imputation method.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline to Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.

Units	Counts
Participants	OG00093 OG00192

Title

Denominators

Categories

Title	Measurements
	OG000-0.11± 0.151 OG001-0.40± 0.131

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	The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.	ANCOVA		0.0962		Difference in Least Square (LS) Means	-0.29	Standard Error of the Mean	0.173	2-Sided	95	-0.628	0.051					Superiority

Secondary

Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo

An ANCOVA model was used for the analysis.

ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts & washout imputation method.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline to Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

An ANCOVA model was used for the analysis.

Posted

Least Squares Mean

Standard Error

millimole per liter (mmol/L)

Baseline to Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
OG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.

Secondary

Change From Baseline in Body Weight at Week 26

An ANCOVA model was used for the analysis.

Posted

Least Squares Mean

Standard Error

kilogram (kg)

Baseline to Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
OG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.

Secondary

Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg

An ANCOVA model was used for the analysis.

Analysis population included all participants with baseline SBP ≥130 mmHg in ITT population where, ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data are imputed using control-based copy reference multiple imputation under the missing not at random framework.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
OG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.

Secondary

Change From Baseline in SBP at Week 12 for All Participants

An ANCOVA model was used for the analysis.

ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data are imputed using control-based copy reference multiple imputation under the missing not at random framework.

Posted

Least Squares Mean

Standard Error

mmHg

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
OG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.

Secondary

Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g)

An ANCOVA model was used for analysis. No Measure of Dispersion was pre-specified to be calculated.

Analysis population included all participants with baseline UACR > 30 mg/g in ITT population where, ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts & washout imputation method.

Posted

Geometric Mean

Standard Error

percent change

Baseline to Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
OG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.

Secondary

Percentage of Participants With HbA1c <6.5% at Week 26

ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures.

Posted

Number

percentage of participants

Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
OG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.

Units	Counts
Participants

Secondary

Percentage of Participants With HbA1c <7.0% at Week 26

ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures.

Posted

Number

percentage of participants

Week 26

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
OG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.

Units	Counts
Participants

Secondary

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the investigational medicinal product (IMP).

Safety population included all randomized participants who received at least one dose of double-blind IMP. Two participants were randomized to Sotagliflozin 400 mg and dosed with Sotagliflozin 200 mg and 400 mg treatments during the study. Data for these participants were summarized in the Sotagliflozin 200 mg arm in the safety population.

Posted

Number

percentage of participants

First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
OG002	Sotagliflozin 400 mg

Other Pre-specified

Percentage of Participants With Hypoglycemic Events

Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia [typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L)]; Severe [an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions] or documented symptomatic hypoglycemia [typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL].

Safety population included all randomized participants who received at least 1 dose of double-blind investigational medicinal product (IMP) (regardless of the amount of treatment administered).

Posted

Number

percentage of participants

up to 56.3 weeks

ID	Title	Description
OG000	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.
OG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.

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	Placebo	Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks.	6	93	21	93	44	93
EG001	Sotagliflozin 200 mg	Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.	6	94	18	94	44	94
EG002	Sotagliflozin 400 mg	Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.	3	90	20	90	29	90

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0022 affected90 at risk
Peripheral ischaemia	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0022 affected90 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Asthenia	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Death	General disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Sudden cardiac death	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Alanine aminotransferase increased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Glomerular filtration rate decreased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Hepatitis C antibody positive	Investigations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0002 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0004 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0021 affected90 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Cardiac failure	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0002 affected93 at risk EG0011 affected94 at risk EG0021 affected90 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0002 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0002 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Coronary artery disease	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Diastolic dysfunction	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Myocardial infarction	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0011 affected94 at risk EG0021 affected90 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Chronic respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Painful respiration	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0022 affected90 at risk
Tracheomalacia	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Blood loss anaemia	Blood and lymphatic system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Peripheral sensorimotor neuropathy	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Sciatica	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Syncope	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Eye haemorrhage	Eye disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Obstructive pancreatitis	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0006 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
End stage renal disease	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0012 affected94 at risk EG0023 affected90 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Renal colic	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Renal failure	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0012 affected94 at risk EG0021 affected90 at risk
Renal impairment	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0021 affected90 at risk
Fistula	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Metatarsalgia	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0012 affected94 at risk EG0020 affected90 at risk
Bronchitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Cellulitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Gangrene	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Herpes zoster	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Influenza	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0010 affected94 at risk EG0021 affected90 at risk
Osteomyelitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Pneumonia	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0024 affected90 at risk
Pneumonia bacterial	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0011 affected94 at risk EG0020 affected90 at risk
Sepsis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0001 affected93 at risk EG0010 affected94 at risk EG0020 affected90 at risk
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 affected93 at risk EG0012 affected94 at risk EG0020 affected90 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG0005 affected93 at risk EG0011 affected94 at risk EG0023 affected90 at risk
Glomerular filtration rate decreased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0003 affected93 at risk EG00110 affected94 at risk EG0028 affected90 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0003 affected93 at risk EG0015 affected94 at risk EG0025 affected90 at risk
Renal impairment	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0007 affected93 at risk EG0015 affected94 at risk EG0023 affected90 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0005 affected93 at risk EG0013 affected94 at risk EG0022 affected90 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0002 affected93 at risk EG0019 affected94 at risk EG0025 affected90 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0006 affected93 at risk EG0012 affected94 at risk EG0021 affected90 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0006 affected93 at risk EG0019 affected94 at risk EG0023 affected90 at risk
Influenza	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0005 affected93 at risk EG0015 affected94 at risk EG0022 affected90 at risk
Nasopharyngitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0004 affected93 at risk EG0018 affected94 at risk EG0021 affected90 at risk
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG00016 affected93 at risk EG00110 affected94 at risk EG0026 affected90 at risk

Ancestor Terms

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D003924	Diabetes Mellitus, Type 2
D051436	Renal Insufficiency, Chronic