Type 2 Diabetes Evaluation of Ranolazine in Subjects With... | NCT01425359

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Qualifying phase: Participants will enter a 2-week washout period if needing to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period will be randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.	Drug: Ranolazine placebo
Ranolazine	Experimental	Qualifying phase: Participants will enter a 2-week washout period if needing to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period will be randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.	Drug: Ranolazine Drug: Ranolazine placebo

Name	Type	Description	Arm Group Labels	Other Names
Ranolazine	Drug		Ranolazine	Ranexa®
Ranolazine placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment	Average weekly angina frequency was defined as the total number of angina episodes reported during the last 6 weeks of treatment divided by 6 weeks. For subjects who terminated with less than 6 weeks of treatment, frequency was calculated as the total number of angina episodes reported during the treatment period divided by the subject's actual duration of treatment.	6 weeks

Secondary Outcomes

Measure	Description	Time Frame
Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment	Average weekly frequency of sublingual nitroglycerin use was defined as the total number reported during the last 6 weeks of treatment divided by the duration corresponding to the last 6 weeks of treatment.	6 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent
Males and females aged at least 18 years
At least a 3-month history of chronic stable angina triggered by physical effort and relieved by rest and/or sublingual nitroglycerin
CAD documented by one or more of the following:
1. Angiographic evidence of ≥ 50% stenosis of one or more major coronary arteries
2. History of myocardial infarction (MI) documented by positive myocardial muscle creatine kinase (CK-MB) enzymes, troponins, or electrocardiogram (ECG) changes
3. Cardiac imaging study or exercise test diagnostic for CAD
Treatment with up to 2 antianginal therapies at a stable dose for at least 2 weeks prior to the Qualifying Period.
Documented history of T2DM
Willing to maintain stable tobacco usage habits throughout the study
Willing to maintain stable activity levels throughout the study
Females of childbearing potential must agree to utilize highly effective contraception methods from Screening throughout the duration of study treatment and for 14 days following the last dose of study drug.

Exclusion Criteria:

New York Heart Association (NYHA) Class III and IV
Acute coronary syndrome in the prior 2 months or planned coronary revascularization during the study period
Stroke or transient ischemic attack within 6 months prior to Screening
QTc > 500 milliseconds
Uncontrolled hypertension (seated systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg)
Systolic blood pressure < 100 mmHg
Clinically significant hepatic impairment
Prior treatment with ranolazine, or known hypersensitivity or intolerance to ranolazine
Females who are breastfeeding
Positive serum pregnancy test
Participation in another investigational drug or device study within 1 month prior to Screening
Current treatment with trimetazidine, ivabradine, or nicorandil. Subjects will need to discontinue these medications 2 weeks prior to the Qualifying Period.
Current treatment with potent inhibitors of cytochrome (CYP)3A (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
Current treatment with CYP3A and P glycoprotein (Pgp) inducers (eg, rifampicin/rifampin, carbamazepine, and St. John's wort [Hypericum perforatum])
Current treatment with CYP3A4 substrates with a narrow therapeutic range (eg, cyclosporine, tacrolimus, and sirolimus)
Subjects taking simvastatin who cannot reduce the dose to 20 mg once daily or who cannot switch to another statin
Current treatment with Class I or III antiarrhythmic medications
History of illicit drug use or alcohol abuse within 1 year of Screening
Any other conditions that, in the opinion of the investigator, are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the study

Name	Affiliation	Role
Patrick Yue, MD	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Cardiology and Medicine Clinic		Little Rock	Arkansas	72204	United States
Merced Heart Associates

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25249560	Derived	Arnold SV, Kosiborod M, Li Y, Jones PG, Yue P, Belardinelli L, Spertus JA. Comparison of the Seattle Angina Questionnaire With Daily Angina Diary in the TERISA Clinical Trial. Circ Cardiovasc Qual Outcomes. 2014 Nov;7(6):844-50. doi: 10.1161/CIRCOUTCOMES.113.000752. Epub 2014 Sep 23.
24978650	Derived	Roubinian NH, Escobar GJ, Liu V, Gardner MN, Carson JL, Kleinman SH, Murphy EL; NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS-III). Decreased red blood cell use and mortality in hospitalized patients. JAMA Intern Med. 2014 Aug;174(8):1405-7. doi: 10.1001/jamainternmed.2014.2889. No abstract available.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.
BG001	Ranolazine	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.
BG002	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
	BG00064± 8.5 BG00163± 8.6 BG00264± 8.5

Age, Customized

Number

participants

Title

Denominators

Categories

< 65 years

Title	Measurements
	BG000249 BG001264 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000182 BG001180 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG0001 BG0011 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG0005 BG0014 BG002

Region of Enrollment

All randomized participants were analyzed for region of enrollment (placebo, n = 476; ranolazine, n = 473).

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00012 BG00115 BG002

Body Mass Index

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00031.1± 4.90 BG00131.3± 5.01 BG002

Glycosylated hemoglobin (HbA1c)

Mean

Standard Deviation

percent HbA1c in blood

Title

Denominators

Categories

Title	Measurements
	BG0007.3± 1.53 BG0017.3± 1.50 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

Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment

Average weekly angina frequency was defined as the total number of angina episodes reported during the last 6 weeks of treatment divided by 6 weeks.

For subjects who terminated with less than 6 weeks of treatment, frequency was calculated as the total number of angina episodes reported during the treatment period divided by the subject's actual duration of treatment.

Full Analysis Set (FAS): randomized participants who received at least 1 dose of randomized study drug with at least 1 postbaseline primary efficacy measurement and did not have any major eligibility violations. Participants were included in the FAS if they did not discontinue study drug prior to Day 14.

Posted

Mean

Standard Deviation

angina attacks per week

6 weeks

ID	Title	Description
OG000	Placebo	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.
OG001	Ranolazine	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Units	Counts
Participants	OG000465 OG001462

Title

Denominators

Categories

Title	Measurements
	OG0005.2± 4.73 OG0014.5± 4.32

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		Generalized linear model		0.008	Angina frequency was compared by fitting a generalized linear model with log link and negative binomial distribution response.					2-Sided							No	Superiority or Other

Secondary

Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment

Average weekly frequency of sublingual nitroglycerin use was defined as the total number reported during the last 6 weeks of treatment divided by the duration corresponding to the last 6 weeks of treatment.

Full Analysis Set

Posted

Mean

Standard Deviation

nitroglycerin uses per week

6 weeks

ID	Title	Description
OG000	Placebo	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.
OG001	Ranolazine	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Secondary

Percentage of Weeks Participants Achieved at Least a 50% Reduction in Angina Frequency

For each participant, the percentage of the last 6 weeks on treatment during which the angina frequency was less than or equal to 50% of the baseline average weekly angina frequency was determined.

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

Posted

Mean

Standard Deviation

percentage of weeks

6 weeks

ID	Title	Description
OG000	Placebo	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.
OG001	Ranolazine	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Secondary

Percentage of the Last 6 Weeks on Treatment During Which the Angina Frequency Was ≤ 50% of the Baseline Average Weekly Angina Frequency

Full Analysis Set

Posted

Mean

Standard Error

percentage of weeks

6 weeks

ID	Title	Description
OG000	Placebo	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.
OG001	Ranolazine	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Secondary

Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores

The range of each health domain score is 0-100, with 0 indicating a poorer health state and 100 indicating a better health state. An increase in score indicates an improvement in health state. Participants were asked to complete the survey at randomization (prior to receiving treatment), and at end of treatment visit (Week 8) or early study drug discontinuation or early termination visit. The survey asked participants for responses specific to the preceding 4 weeks prior to completing the survey.

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

Posted

Mean

Standard Error

units on a scale

Up to 8 weeks

ID	Title	Description
OG000	Placebo	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.
OG001	Qualifying Phase: Participants Entered a 2-week Washout Period	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Secondary

Patient's Global Impression of Change (PGIC) Scale Score

The PGIC was completed at the end of treatment/last visit.The PGIC scale measures the change in the participant's overall status since the beginning of the study on a scale ranging from 1 (no change or worse) to 7 (very much improved).

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

Posted

Mean

Standard Error

units on a scale

8 weeks

ID	Title	Description
OG000	Placebo	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.
OG001	Ranolazine	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 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	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.			20	474	0	474
EG001	Ranolazine	Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period. Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.			16	470	0	470

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0003 affected474 at risk EG0012 affected470 at risk
Angina unstable	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0013 affected470 at risk
Angina pectoris	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0011 affected470 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0002 affected474 at risk EG0010 affected470 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected474 at risk EG0011 affected470 at risk
Cardiogenic shock	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected474 at risk EG0011 affected470 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0003 affected474 at risk EG0010 affected470 at risk
Coronary artery disease	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected474 at risk EG0011 affected470 at risk
Chest pain	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0012 affected470 at risk
Sudden cardiac death	General disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected474 at risk EG0011 affected470 at risk
Thrombosis in device	General disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0000 affected474 at risk EG0011 affected470 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected474 at risk EG0011 affected470 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0003 affected474 at risk EG0011 affected470 at risk
Cervical myelopathy	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Syncope	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected474 at risk EG0011 affected470 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Calculus urinary	Renal and urinary disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk
Circulatory collapse	Vascular disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected474 at risk EG0011 affected470 at risk
Hypertension	Vascular disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected474 at risk EG0010 affected470 at risk

ID	Term
D000787	Angina Pectoris
D003324	Coronary Artery Disease
D003924	Diabetes Mellitus, Type 2

ID	Term
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D014652	Vascular Diseases
D002637	Chest Pain
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D003327	Coronary Disease
D001161	Arteriosclerosis
D001157	Arterial Occlusive Diseases
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds