Efficacy and Safety of Alogliptin Plus Metformin Compared... | NCT00856284

ID	Type	Description
2008-007444-34	Registry Identifier	EudraCT
U1111-1111-7397	Registry Identifier	WHO
HKCTR-862	Registry Identifier	HKUCTR
DOH-27-0709-2825	Registry Identifier	SANCTR
09/H0703/66	Registry Identifier	NRES
NMRR-09-203-3590	Registry Identifier	NMRR

Label	Type	Description	Intervention Names
Metformin + Alogliptin 12.5 mg	Experimental	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.	Drug: Alogliptin Drug: Metformin
Metformin + Alogliptin 25 mg	Experimental	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.	Drug: Alogliptin Drug: Metformin
Metformin + Glipizide	Active Comparator	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.	Drug: Metformin Drug: Glipizide

Name	Type	Description	Arm Group Labels	Other Names
Alogliptin	Drug	Alogliptin tablets	Metformin + Alogliptin 12.5 mg Metformin + Alogliptin 25 mg

Measure	Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52	The change from Baseline to Week 52 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.	Baseline and Week 52
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104	The change from Baseline to Week 104 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.	Baseline and Week 104

Measure	Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin at Other Time Points	The change from Baseline over time in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.	Baseline and Weeks 4, 8, 12, 16, 20, 26, 39, 65, 78, and 91.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a diagnosis of type 2 diabetes mellitus.
Must meet one of the following:
- Has been inadequately controlled on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose) of metformin for at least 2 months prior to Screening.
- Has been inadequately controlled (as defined by a glycosylated hemoglobin 7.5 - 10%, inclusive) on metformin <1500 mg without documented maximum tolerated dose.
No treatment with antidiabetic agents other than metformin within 2 months prior to Screening (for Schedule A)/Pre-Screening (for Schedule B).
Has body mass index within 23 kg/m^2 and 45 kg/m^2 unless the patient is Asian or of Asian descent, for whom the allowable body mass index will be ≥ 20 kg/m^2 and ≤ 35 kg/m^2, inclusive.
Has fasting C-peptide concentration at least 0.8 ng.
If regularly using non-excluded medications, must be on a stable dose at least 4 weeks prior to Screening/Pre-screening.
Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant, lactating or intends to donate ova from Screening throughout the duration of the study.
Must be able and willing to monitor their blood glucose concentrations with a home monitor, and comply with protocol requirements including scheduled clinic appointments.

Exclusion Criteria:

Systolic blood pressure greater than or equal to 150 mmHg and/or diastolic pressure greater than or equal to 90.
Hemoglobin less than or equal to 12 g/dL for males and less than or equal to 10 g/dL for females at Screening Visit.
Alanine aminotransferase greater than or equal to 2.5 times the upper limit of normal at Screening Visit.
Serum creatinine greater than or equal to 1.5 mg/dL for males and 1.4 for females, or calculated creatinine clearance less than 60 L/min.
Males intending to impregnate others or donate sperm before, during or within 1 month after participating in the study.
A history of cancer other than squamous or basal cell carcinoma of the skin that has not been in full remission for at least 5 years.
A history of laser treatment for diabetic retinopathy within 6 months of screening.
Treated for diabetic gastric paresis, gastric banding, or gastric bypass.
New York Heart Association Class III or IV heart failure.
History of coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, stroke or transient ischemic attack within 3 months prior to screening.
Known history of human immunodeficiency virus, hepatitis B or C.
Alcohol or substance abuse within 2 years prior to screening.
Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- Any investigational drug within 30 days
- Any investigational diabetic drug within 3 months
- Any antidiabetic drug in the dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 mimetics classes within 90 days prior to Screening other than metformin
- Prior treatment with alogliptin.
- Weight-loss drugs
- Oral or systemically injected glucocorticoids
A hypersensitivity allergy or anaphylactic reaction to any dipeptidyl peptidase-4 drug, metformin or glipizide.
Has a documented history or concurrent signs of significant thyroid disease (eg, autoimmune thyroid diseases such as Graves disease and Hashimoto thyroiditis or active thyroid nodules).

Name	Affiliation	Role
Medical Director, Clinical Science	Takeda	Study Director

PubMed Identifier	Type	Citation	Retractions
27787778	Derived	Gordon J, McEwan P, Hurst M, Puelles J. The Cost-Effectiveness of Alogliptin Versus Sulfonylurea as Add-on Therapy to Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus. Diabetes Ther. 2016 Dec;7(4):825-845. doi: 10.1007/s13300-016-0206-7. Epub 2016 Oct 27.

ID	Title	Description
FG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
FG001	Metformin + Alogliptin 25 mg

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
	BG00055.2± 9.60 BG00155.5± 9.81 BG00255.4± 9.60 BG003

Age, Customized

Categories ≥65 years and ≥75 years are not mutually exclusive. Participants ≥75 years are counted in both categories.

Number

participants

Title

Denominators

Categories

<65 years

Title	Measurements
	BG000734 BG001710 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000461 BG001433 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG00040 BG00142 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG000192 BG001204 BG002

Body Mass Index (BMI)

BMI data available for 879, 885 and 872 participants in each treatment arm, respectively.

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00031.27± 5.417 BG00131.27± 5.341

Glycosylated hemoglobin (HbA1c)

Mean HbA1c data includes 877, 883 and 870 participants in each treatment arm, respectively.

Mean

Standard Deviation

percentage

Title

Denominators

Categories

Title	Measurements
	BG0007.59± 0.599 BG0017.61± 0.606

Baseline HbA1c Category

Number

participants

Title

Denominators

Categories

<8.0%

Title	Measurements
	BG000615 BG001620 BG002

Diabetes duration

Diabetes duration data available for 880, 884 and 874 participants in each treatment arm, respectively.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0005.65± 5.324 BG0015.42± 4.730

Metformin dose

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG0001825.2± 405.59 BG0011837.2± 373.06 BG002

Glomerular filtration rate

Glomerular filtration rate (GFR) was calculated using the modification of diet in renal disease (MDRD) formula and the Cockcroft-Gault formula. Data include 877, 883 and 870 participants in each treatment arm, respectively.

Mean

Standard Deviation

mL/min/1.73m^2

Title

Denominators

Categories

MDRD

Title	Measurements
	BG00083.04± 16.586 BG001

Smoking history

Number

participants

Title

Denominators

Categories

Never smoked

Title	Measurements
	BG000543 BG001586 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 Glycosylated Hemoglobin (HbA1c) at Week 52

The change from Baseline to Week 52 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.

The Per-protocol set included all randomized patients who took at least 1 dose of double-blind study drug, with a Baseline assessment and at least 1 post-baseline assessment for that variable and who had no major protocol violations. Last observation carried forward (LOCF) was used.

Posted

Least Squares Mean

Standard Error

percentage glycosylated hemoglobin

Baseline and Week 52

ID	Title	Description
OG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG002	Metformin + Glipizide	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Units	Counts
Participants	OG000371 OG001382 OG002336

Title

Denominators

Categories

Title	Measurements
	OG000-0.81± 0.027 OG001-0.76± 0.027 OG002-0.73± 0.029

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
OG001 OG002	The null hypotheses were tested in a fixed order at the 1-sided 0.0125 significance level at Weeks 52 and 104, independently: H01: Alogliptin 25 mg was inferior in HbA1c change from Baseline vs glipizide. H02: Alogliptin 12.5 mg was inferior vs glipizide. H03: Alogliptin 25 mg was not superior vs glipizide. H04: Alogliptin 12.5 mg was not superior vs glipizide. Each subsequent null hypothesis was tested only if all previously tested null hypotheses were rejected with respect to Weeks 52 and 104.					LS Mean Difference	-0.03			1-Sided	98.75		0.059				Yes	Non-Inferiority or Equivalence

Secondary

Change From Baseline in Glycosylated Hemoglobin at Other Time Points

The change from Baseline over time in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.

Per-protocol set; LOCF was used.

Posted

Least Squares Mean

Standard Error

percentage of glycosylated hemoglobin

Baseline and Weeks 4, 8, 12, 16, 20, 26, 39, 65, 78, and 91.

ID	Title	Description
OG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG002	Metformin + Glipizide	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Secondary

Change From Baseline in Fasting Plasma Glucose Over Time

The change from Baseline in fasting plasma glucose (FPG) was assessed at Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104. LS means are from an ANCOVA model with treatment, study schedule, and geographic region as class variables, and Baseline FPG and Baseline metformin dose as covariates.

Full analysis set, which included all randomized patients who received at least 1 dose of double-blind study drug who had a Baseline assessment and at least 1 post-baseline assessment for FPG. LOCF was used.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104.

ID	Title	Description
OG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG002	Metformin + Glipizide	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Secondary

Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%

The percentage of participants with HbA1c less than or equal to 6.5% at Weeks 26, 52, 78, and 104. Participants who did not complete the scheduled Week 104 visit were assessed based on their response at the time of discontinuation.

Full analysis set. Participants who did not complete the scheduled Week 26, Week 52, Week 78 or Week 104 visit were assessed based on their response at the time of discontinuation.

Posted

Number

percentage of participants

Weeks 26, 52, 78, and 104.

ID	Title	Description
OG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG002	Metformin + Glipizide	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Secondary

Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%

Percentage of participants with HbA1c ≤ 7.0% at Weeks 26, 52, 78, and 104. Participants who did not complete the scheduled Week 104 visit were assessed based on their response at the time of discontinuation.

Full analysis set. Participants who did not complete the scheduled Week 26, Week 52, Week 78 or Week 104 visit were assessed based on their response at the time of discontinuation.

Posted

Number

percentage of participants

Weeks 26, 52, 78, and 104.

ID	Title	Description
OG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG002	Metformin + Glipizide	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Secondary

Change From Baseline in Body Weight Over Time

LS Means are from an ANCOVA model with treatment, study schedule and geographic region as class variables, and Baseline weight and Baseline metformin dose as covariates.

Full analysis set, LOCF was used.

Posted

Least Squares Mean

Standard Error

Baseline and Weeks 12, 26, 39, 52, 65, 78, 91, and 104.

ID	Title	Description
OG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG002	Metformin + Glipizide	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.

Primary

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104

The change from Baseline to Week 104 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). The least squares (LS) means are from an analysis of covariance (ANCOVA) model with treatment, study schedule, and geographic region as class variables, and Baseline metformin dose and Baseline HbA1c as covariates.

Posted

Least Squares Mean

Standard Error

percentage glycosylated hemoglobin

Baseline and Week 104

ID	Title	Description
OG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
OG002	Metformin + Glipizide

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery disease	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0005 affected873 at risk EG0013 affected878 at risk EG0022 affected869 at risk
Angina unstable	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0014 affected878 at risk EG0024 affected869 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0025 affected869 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0013 affected878 at risk EG0022 affected869 at risk
Atrial flutter	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0012 affected878 at risk EG0021 affected869 at risk
Cardiac failure	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0013 affected878 at risk EG0021 affected869 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Myocardial infarction	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0023 affected869 at risk
Angina pectoris	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0012 affected878 at risk EG0021 affected869 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0022 affected869 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Cardiomyopathy	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Silent myocardial infarction	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0012 affected878 at risk EG0020 affected869 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Atrioventricular block	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Bradycardia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Coronary artery occlusion	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Left ventricular failure	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Pericardial effusion	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Right ventricular failure	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Cellulitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0003 affected873 at risk EG0011 affected878 at risk EG0023 affected869 at risk
Pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0012 affected878 at risk EG0022 affected869 at risk
Gastroenteritis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0012 affected878 at risk EG0020 affected869 at risk
Dengue fever	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0022 affected869 at risk
Diverticulitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Hepatitis viral	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0022 affected869 at risk
Urinary tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Urosepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Abdominal abscess	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Abscess limb	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Acute sinusitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Amoebiasis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Appendicitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Bronchitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Cystitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Gangrene	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Gastroenteritis salmonella	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Lobar pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Malaria	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Osteomyelitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Pneumocystis jiroveci pneumonia	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Scrotal abscess	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Sepsis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Septic shock	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Staphylococcal infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0023 affected869 at risk
Syncope	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Dizziness	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Epilepsy	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0012 affected878 at risk EG0020 affected869 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Cerebral infarction	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Intercostal neuralgia	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Neuralgia	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Parkinsonism	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Presyncope	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Radiculopathy	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Tension headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
VIIth nerve paralysis	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
VIth nerve paralysis	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Vertebrobasilar insufficiency	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0013 affected878 at risk EG0024 affected869 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0012 affected878 at risk EG0021 affected869 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Myalgia intercostal	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Polymyositis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Colitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0012 affected878 at risk EG0020 affected869 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0022 affected869 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Anal fistula	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Diverticulum	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Gastritis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Mallory-Weiss syndrome	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Umbilical hernia, obstructive	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Colon cancer stage 0	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Endometrial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Gastrointestinal tract adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Non-small cell lung cancer stage IIIB	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Ovarian adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Rectal cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Renal oncocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Small cell lung cancer stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0012 affected878 at risk EG0021 affected869 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0022 affected869 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Comminuted fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Incisional hernia	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Peripheral nerve injury	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0012 affected878 at risk EG0023 affected869 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0012 affected878 at risk EG0020 affected869 at risk
Renal colic	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Calculus urinary	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Diabetic nephropathy	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Urinary retention	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0013 affected878 at risk EG0020 affected869 at risk
Hypertensive crisis	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0012 affected878 at risk EG0021 affected869 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Aortic aneurysm	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Arterial thrombosis limb	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Embolism	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Femoral artery occlusion	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Iliac artery occlusion	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Thrombophlebitis	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Non-cardiac chest pain	General disorders	MedDRA 15.0	Systematic Assessment	EG0003 affected873 at risk EG0014 affected878 at risk EG0023 affected869 at risk
Chest pain	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0012 affected878 at risk EG0020 affected869 at risk
Hernia	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Sudden death	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Granulomatous pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Adenomyosis	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Cervical dysplasia	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Cervix disorder	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Cystocele	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Epididymitis	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Rectocele	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Uterine prolapse	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Uterovaginal prolapse	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0013 affected878 at risk EG0020 affected869 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Cataract	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0011 affected878 at risk EG0021 affected869 at risk
Cataract nuclear	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Cataract subcapsular	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Iridocyclitis	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Retinal detachment	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Vision blurred	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Bipolar disorder	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Depressed mood	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Depression	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Schizophrenia	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Acute vestibular syndrome	Ear and labyrinth disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Primary hyperaldosteronism	Endocrine disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected873 at risk EG0010 affected878 at risk EG0020 affected869 at risk
Abortion	Pregnancy, puerperium and perinatal conditions	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0010 affected878 at risk EG0021 affected869 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected873 at risk EG0011 affected878 at risk EG0020 affected869 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00060 affected873 at risk EG00160 affected878 at risk EG00263 affected869 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00084 affected873 at risk EG00190 affected878 at risk EG00276 affected869 at risk
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00078 affected873 at risk EG00167 affected878 at risk EG00261 affected869 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG00016 affected873 at risk EG00137 affected878 at risk EG00232 affected869 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG00028 affected873 at risk EG00132 affected878 at risk EG00220 affected869 at risk
Fatigue	General disorders	MedDRA 15.0	Systematic Assessment	EG00020 affected873 at risk EG00119 affected878 at risk EG00228 affected869 at risk
Asthenia	General disorders	MedDRA 15.0	Systematic Assessment	EG00014 affected873 at risk EG00115 affected878 at risk EG00227 affected869 at risk
Influenza	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00036 affected873 at risk EG00136 affected878 at risk EG00242 affected869 at risk
Urinary tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00041 affected873 at risk EG00133 affected878 at risk EG00238 affected869 at risk
Bronchitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00039 affected873 at risk EG00136 affected878 at risk EG00236 affected869 at risk
Sinusitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00026 affected873 at risk EG00129 affected878 at risk EG00223 affected869 at risk
Creatinine renal clearance decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG00023 affected873 at risk EG00134 affected878 at risk EG00232 affected869 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG00018 affected873 at risk EG0016 affected878 at risk EG00291 affected869 at risk
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG00022 affected873 at risk EG00120 affected878 at risk EG00234 affected869 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00054 affected873 at risk EG00145 affected878 at risk EG00249 affected869 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00038 affected873 at risk EG00142 affected878 at risk EG00240 affected869 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG00028 affected873 at risk EG00128 affected878 at risk EG00233 affected869 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00045 affected873 at risk EG00160 affected878 at risk EG00246 affected869 at risk
Dizziness	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00024 affected873 at risk EG00124 affected878 at risk EG00229 affected869 at risk
Tremor	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0005 affected873 at risk EG0013 affected878 at risk EG00229 affected869 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG00035 affected873 at risk EG00126 affected878 at risk EG00233 affected869 at risk
Hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG00045 affected873 at risk EG00167 affected878 at risk EG00265 affected869 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Montgomery	Alabama		United States

ID	Term
D003924	Diabetes Mellitus, Type 2
D003920	Diabetes Mellitus
D006946	Hyperinsulinism
D006943	Hyperglycemia
D018149	Glucose Intolerance

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals
D013453	Sulfonylurea Compounds
D013450	Sulfones
D013457	Sulfur Compounds

ID	Title	Description
BG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
BG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.
BG002	Metformin + Glipizide	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Metformin + Alogliptin 12.5 mg	Alogliptin 12.5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.	86	873	688	873
EG001	Metformin + Alogliptin 25 mg	Alogliptin 25 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks.	97	878	687	878
EG002	Metformin + Glipizide	Glipizide 5 mg, tablets, orally, once daily and the maximum tolerated dose of metformin (1500 mg to 3300 mg daily) for up to 104 weeks. After at least 2 weeks of treatment but prior to Week 20, participants with persistent hyperglycemia (fasting plasma glucose ≥250 mg/dL) underwent a dose titration of glipizide up to 20 mg in 5-mg increments in 4-week intervals.	81	869	668	869