Comparison of Fasiglifam (TAK-875) to Placebo and Sitagli... | NCT01549964

ID	Type	Description
2011-001752-10	EudraCT Number
U1111-1124-2225	Registry Identifier	WHO
NMRR-12-446-11314	Registry Identifier	NMRR (Malaysia)

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Fasiglifam (TAK-875) 25 mg	Experimental	Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Drug: Fasiglifam (TAK-875)
Fasiglifam (TAK-875) 50 mg	Experimental	Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Drug: Fasiglifam (TAK-875)
Sitagliptin 100 mg	Active Comparator	Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. TAK-875 placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	Drug: Sitagliptin
Placebo	Placebo Comparator	Fasiglifam (TAK-875) placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Name	Type	Description	Arm Group Labels	Other Names
Fasiglifam (TAK-875)	Drug	Fasiglifam (TAK-875) tablets	Fasiglifam (TAK-875) 25 mg Fasiglifam (TAK-875) 50 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to Baseline. A Mixed Model Repeated Measures (MMRM) model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.	Baseline and Week 24

Secondary Outcomes

Measure	Description	Time Frame
Incidence of HbA1c <7%	Incidence (percentage) of participants with glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than 7% at Week 24.	24 Weeks
Change From Baseline in Fasting Plasma Glucose (FPG)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The participant is male or female and 18 years of age or older with a historical diagnosis of type II diabetes mellitus.
The participant meets one of the following criteria:
1. The participant has an HbA1c level ≥7.5 and <10.5%, and has been on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose [MTD]) of metformin for at least 2 months prior to Screening. This participant will immediately enter the Placebo Run-in Period according to Study Schedule A, or;
2. The participant has an HbA1c level ≥7.5 and <10.5%, and has been on a stable daily dose of <1500 mg of metformin without documented MTD for at least 2 months prior to Screening. After completing the Screening Visit, this participant will have their metformin dose immediately increased to ≥1500 mg (or MTD) for an 8-week Titration Period according to Study Schedule B. Following this 8-week period, the participant must qualify for entry into the Placebo Run-in Period by completing the Week -3 procedures including having an HbA1c level ≥7.5 and <10.5%.
The participant has had no treatment with antidiabetic agents other than metformin within 2 months prior to Screening (Exception: if a participant has received other antidiabetic therapy for ≤7 days within the 2 months prior to Screening).
The participant has a body mass index (BMI) ≤45 kg/m² at Screening.
Participants regularly using other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. However, PRN (as needed) use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
The participant is able and willing to monitor glucose with a home glucose monitor and consistently record his or her own blood glucose concentrations and complete subject diaries.

Exclusion Criteria:

The participant donated or received any blood products within 12 weeks prior to Screening or is planning to donate blood during the study.
Hemoglobin ≤12 g/dL (≤120 g/L) for males and ≤10 g/dL (≤100 g/L) for females at Screening Visit.
The participant has systolic blood pressure ≥160 mm Hg or diastolic pressure ≥95 mm Hg at Screening Visit. (If the participant meets this exclusion criterion, the assessment may be repeated once at least 30 minutes after the initial measurement.)
The participant has a history of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
The participant has had treatment for gastric banding or gastric bypass surgery within one year prior to Screening.
The participant had coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, unstable angina pectoris, clinically significant abnormal ECG, cerebrovascular accident or transient ischemic attack within 3 months prior to or at Screening.

Name	Affiliation	Role
Senior Medical Director Clinical Science	Takeda	Study Director

PubMed Identifier	Type	Citation	Retractions
30880443	Derived	Shavadia JS, Sharma A, Gu X, Neaton J, DeLeve L, Holmes D, Home P, Eckel RH, Watkins PB, Granger CB. Determination of fasiglifam-induced liver toxicity: Insights from the data monitoring committee of the fasiglifam clinical trials program. Clin Trials. 2019 Jun;16(3):253-262. doi: 10.1177/1740774519836766. Epub 2019 Mar 18.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
BG001	Sitagliptin 100 mg	Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
BG002	Fasiglifam 25 mg	Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
BG003	Fasiglifam 50 mg	Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
BG004	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
	BG00055.6± 9.72 BG00155.8± 9.84 BG00256.3± 9.58 BG003

Age, Customized

Number

participants

Title

Denominators

Categories

< 65 years

Title	Measurements
	BG000107 BG001214 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00066 BG001103 BG002

Race/Ethnicity, Customized

Race data is available for 260 participants in the fasiglifam 50 mg treatment arm.

Number

participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG0000 BG0010 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG00013 BG00129 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Australia

Title	Measurements
	BG0003 BG0015 BG002

Weight

Weight data is available for 260 participants in the fasiglifam 50 mg treatment arm.

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00091.15± 18.988 BG00191.41± 19.664

Height

Height data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000168.2± 10.08 BG001169.4± 10.74

Body Mass Index (BMI)

BMI data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00032.06± 5.070 BG00131.68

BMI Category

BMI data is available for 262 and 260 participants in the fasiglifam 25 mg and fasiglifam 50 mg treatment arms, respectively.

Number

participants

Title

Denominators

Categories

< 30 kg/m^2

Title	Measurements
	BG00053 BG001106 BG002

Glycosylated Hemoglobin (HbA1c)

HbA1c data is available for 258 and 260 participants in the sitagliptin 100 mg and fasiglifam 50 mg treatment arms, respectively.

Mean

Standard Deviation

percent

Title

Denominators

Categories

Title	Measurements
	BG0008.34± 0.739 BG0018.35

HbA1c Category

HbA1c data is available for 260 participants in the fasiglifam 50 mg treatment arm.

Number

participants

Title

Denominators

Categories

< 8.5%

Title	Measurements
	BG00080 BG001156 BG002

Duration of Diabetes

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0006.655± 6.262 BG0015.940± 4.942 BG002

Fasting Plasma Glucose

Data is only available for 258 and 259 participants in the sitagliptin 100 mg and fasiglifam 50 mg treatment arms, respectively.

Mean

Standard Deviation

ng/dL

Title

Denominators

Categories

Title	Measurements
	BG000178.4± 36.94 BG001175.6

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)

The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 24 relative to Baseline. A Mixed Model Repeated Measures (MMRM) model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.

Full Analysis Set included all randomized participants who received at least 1 dose of study drug analyzed according to the treatment group to which they were randomized. A participant was included in the analyses when there was both a Baseline and at least 1 Post-baseline value at Week 24.

Posted

Least Squares Mean

Standard Error

Percent

Baseline and Week 24

ID	Title	Description
OG000	Placebo	Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
OG001	Sitagliptin 100 mg	Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
OG002	Fasiglifam 25 mg	Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
OG003	Fasiglifam 50 mg	Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Units	Counts
Participants	OG00067 OG001145 OG002144 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.19± 0.098 OG001-1.07± 0.074 OG002-0.75± 0.073 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		Mixed model for repeated measurements		<0.001	MMRM model with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with baseline value and baseline value by visit interaction as covariates with an unstructured covariance structure.	LS Mean Difference	-0.55	Standard Error of the Mean	0.108	2-Sided	95	-0.77	-0.34				No	Superiority or Other

Secondary

Incidence of HbA1c <7%

Incidence (percentage) of participants with glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) less than 7% at Week 24.

Full Analysis Set included all randomized participants who received at least 1 dose of study drug analyzed according to the treatment group to which they were randomized

Posted

Number

percentage of participants

24 Weeks

ID	Title	Description
OG000	Placebo	Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
OG001	Sitagliptin 100 mg	Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG)

The change between FPG collected at week 24 relative to Baseline. A MMRM model was used for analysis with treatment, country, schedule, visit and visit by treatment interaction as fixed factors and with Baseline value and Baseline value by visit interaction as covariates with an unstructured covariance structure.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline and Week 24

ID	Title	Description
OG000	Placebo	Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.
OG001	Sitagliptin 100 mg	Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	2	132	17	132
EG001	Sitagliptin 100 mg	Sitagliptin 100 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Fasiglifam placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	10	260	16	260
EG002	Fasiglifam 25 mg	Fasiglifam 25 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	14	263	18	263
EG003	Fasiglifam 50 mg	Fasiglifam 50 mg, tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Sitagliptin placebo-matching tablets, orally, once daily for a 24-week Treatment Period followed by an optional 80-week extension period for up to 104 weeks of treatment. Metformin ≥1500 mg or Maximum Tolerated Dose (MTD) needs to continue at a stable dose.	4	260	20	260

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG0030 affected260 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Angina unstable	Cardiac disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Phimosis	Congenital, familial and genetic disorders	MedDRA 16.1	Systematic Assessment		EG0001 affected132 at risk EG0010 affected260 at risk EG0020 affected263 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Liver disorder	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Gangrene	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Hepatitis B	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Bronchopneumonia	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Pneumonia	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0020 affected263 at risk EG003
Sepsis	Infections and infestations	MedDRA 16.1	Systematic Assessment	One treatment-emergent death occurred during treatment with sitagliptin and is not related.	EG0000 affected132 at risk EG0012 affected260 at risk EG0020 affected263 at risk EG003
Erysipelas	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Liver function test abnormal	Investigations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Carotid bruit	Investigations	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Breast cancer female	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Tumour of ampulla of Vater	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	One treatment-emergent death occurred during treatment with placebo and is not related.	EG0001 affected132 at risk EG0010 affected260 at risk EG0020 affected263 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Syncope	Nervous system disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Radiculopathy	Nervous system disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Depression	Psychiatric disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0020 affected263 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0021 affected263 at risk EG003
Peripheral vascular disorder	Vascular disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0011 affected260 at risk EG0020 affected263 at risk EG003
Peripheral artery stenosis	Vascular disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0020 affected263 at risk EG003
Hypertension	Vascular disorders	MedDRA 16.1	Systematic Assessment		EG0000 affected132 at risk EG0010 affected260 at risk EG0020 affected263 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Muscle Shoals	Alabama		United States

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment		EG00014 affected132 at risk EG0019 affected260 at risk EG00211 affected263 at risk EG0037 affected260 at risk
Nasopharyngitis	Infections and infestations	MedDRA 16.1	Systematic Assessment		EG0003 affected132 at risk EG0018 affected260 at risk EG0027 affected263 at risk EG003