Efficacy and Safety of Linagliptin in Combination With In... | NCT00954447

ID	Type	Description	Link
2008-008296-33	EudraCT Number	EudraCT

Official Title

A Phase III Randomised, Double-blind, Placebo-controlled, Parallel Group Efficacy and Safety Study of Linagliptin (5 mg), Administered Orally Once Daily for at Least 52 Weeks in Type 2 Diabetic Patients in Combination With Basal Insulin Therapy

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Linagliptin	Experimental	patient receives a tablet with intended final marketed dose	Drug: Linagliptin
Placebo	Placebo Comparator	patient receives a tablet identical to those containing Linagliptin	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo, identical to Linagliptin tablet	Placebo
Linagliptin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1c After 24 Weeks	HbA1c is measured as a percentage. Adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant Oral antidiabetic drugs (OAD)	Baseline and 24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Number of Patients With HbA1c < 7.0 Percent		24 and 52 weeks
Number of Patients Lowering HbA1c by at Least 0.5 Percent		24 and 52 weeks
Change From Baseline in HbA1c by Visit at Week 6

Measure	Description	Time Frame
Number of Patients With HbA1c < 6.5 Percent		24 and 52 weeks

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1218.36.01043 Boehringer Ingelheim Investigational Site		Escondido	California		United States
1218.36.01051 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25629790	Derived	Sheu WH, Park SW, Gong Y, Pinnetti S, Bhattacharya S, Patel S, Seck T, Woerle HJ. Linagliptin improves glycemic control after 1 year as add-on therapy to basal insulin in Asian patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015 Mar;31(3):503-12. doi: 10.1185/03007995.2015.1010638. Epub 2015 Feb 13.
24062327	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
BG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
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
	BG00060.4± 10.0 BG00159.7± 9.9 BG00260.0± 10.0

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000301 BG001302 BG002

Baseline HbA1c

Baseline HbA1c was defined as the last available HbA1c measurement prior to the start of randomised study treatment.There were 617 patients with non-missing baseline HbA1c in Placebo group and 618 patients with non-missing values in Linagliptin 5 mg.

Mean

Standard Deviation

Percentage

Title

Denominators

Categories

Title	Measurements
	BG0008.29± 0.85 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in HbA1c After 24 Weeks

HbA1c is measured as a percentage. Adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant Oral antidiabetic drugs (OAD)

The Full Analysis Set (FAS) with a last observation carried forward (LOCF) approach. The FAS comprises all randomised patients who were treated with at least one dose of study medication, had a baseline HbA1c measurement, and had at least one on-treatment HbA1c measurement within the first 24 weeks of double-blind treatment.

Posted

Mean

Standard Error

Percentage

Baseline and 24 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants	OG000617 OG001618

Title

Denominators

Categories

Title	Measurements
	OG0000.07± 0.08 OG001-0.58± 0.08

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		ANCOVA		<0.0001		Mean Difference (Final Values)	-0.65	Standard Error of the Mean	0.05		95	-0.74	-0.55			Linagliptin 5mg - Placebo	No	Superiority or Other

Secondary

Number of Patients With HbA1c < 7.0 Percent

FAS using the non-completers considered failure (NCF) approach, in which missing data due to premature discontinuation of a patient were considered as failure.

Posted

Number

Participants

24 and 52 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Number of Patients Lowering HbA1c by at Least 0.5 Percent

FAS (NCF)

Posted

Number

Participants

24 and 52 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in HbA1c by Visit at Week 6

Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs

FAS (LOCF)

Posted

Mean

Standard Error

Percentage

Baseline and 6 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in HbA1c by Visit at Week 12

Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs

FAS (LOCF)

Posted

Mean

Standard Error

Percentage

Baseline and 12 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in HbA1c by Visit at Week 18

Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs

FAS (LOCF)

Posted

Mean

Standard Error

Percentage

Baseline and 18 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in HbA1c by Visit at Week 32

Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs

FAS (LOCF)

Posted

Mean

Standard Error

Percentage

Baseline and 32 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in HbA1c by Visit at Week 40

Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs

FAS (LOCF)

Posted

Mean

Standard Error

Percentage

Baseline and 40 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in HbA1c by Visit at Week 52

Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs

FAS (LOCF)

Posted

Mean

Standard Error

Percentage

Baseline and 52 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at 24 Weeks of Treatment

Means adjusted for treatment, baseline HbA1c, baseline FPG, categorical renal function impairment and concomitant OADs

FAS (LOCF), further restricted to patients with a baseline FPG measurement and at least one on-treatment FPG measurement

Posted

Mean

Standard Error

mg/dL

Baseline and 24 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment

FAS (LOCF), further restricted to patients with a baseline FPG measurement and at least one on-treatment FPG measurement

Posted

Mean

Standard Deviation

mg/dL

Baseline and 52 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in FPG

FAS, observed cases (OC)

Posted

Mean

Standard Deviation

mg/dL

Baseline, 6, 12, 18, 24, 32 and 40 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in Mean Insulin Dose at 52 Weeks of Treatment

Means adjusted for treatment, continous baseline HbA1c, continous baseline weight, continous baseline Insulin, categorical renal function impairment and concomitant OADs

FAS (LOCF)

Posted

Mean

Standard Error

International units (IU)

Baseline and 52 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units

Secondary

Change From Baseline in Weighted Mean Daily Glucose After 24 and 52 Weeks of Treatment

Mean Daily Glucose was calculated using the 8-point blood glucose profile

FAS (OC)

Posted

Mean

Standard Deviation

mmol*hr/L

Baseline, 24 and 52 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Secondary

Change From Baseline in Incremental Post-prandial Glucose (iPPG) After 24 Weeks of Treatment

FAS (OC)

Posted

Mean

Standard Deviation

mmol*hr/L

Baseline and 24 weeks: post-breakfast, post-lunch, post-dinner

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Other Pre-specified

Number of Patients With HbA1c < 6.5 Percent

FAS (NCF)

Posted

Number

Participants

24 and 52 weeks

ID	Title	Description
OG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.
OG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Patients randomized to receive treatment with matching placebo, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.			83	630	354	630
EG001	Linagliptin 5 mg	Patients randomized to receive treatment with Linagliptin 5mg, orally taken, once daily. During the first 24 weeks of the randomised treatment period, the background dose of basal insulin and/or oral antidiabetic agents was to remain stable. From 24 weeks after randomisation until the end of the trial, adjustments to the dose of basal insulin (but not oral antidiabetic agents) were permitted.			87	631	354	631

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0012 affected631 at risk
Angina pectoris	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0012 affected631 at risk
Angina unstable	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0013 affected631 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Cardiac failure	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0013 affected631 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0011 affected631 at risk
Cardiogenic shock	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Coronary artery disease	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected630 at risk EG0012 affected631 at risk
Coronary artery occlusion	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Myocardial infarction	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0011 affected631 at risk
Silent myocardial infarction	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Cataract	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0012 affected631 at risk
Diplopia	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Retinal detachment	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Retinopathy proliferative	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Vitreous adhesions	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Vitreous haemorrhage	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Abdominal hernia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Diverticulum intestinal haemorrhagic	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0012 affected631 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Mallory-Weiss syndrome	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Megacolon	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Chest pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Death	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Non-cardiac chest pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Pyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Sudden death	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0012 affected631 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Hepatic cyst	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Appendicitis perforated	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Beta haemolytic streptococcal infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Bronchitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0012 affected631 at risk
Bronchopneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Cellulitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Cellulitis of male external genital organ	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Erysipelas	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0011 affected631 at risk
Gangrene	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Gastroenteritis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0012 affected631 at risk
Infected skin ulcer	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Influenza	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Localised infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Meningitis streptococcal	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Orchitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Osteomyelitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0004 affected630 at risk EG0013 affected631 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Staphylococcal infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Streptococcal infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0011 affected631 at risk
Urosepsis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0010 affected631 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0012 affected631 at risk
Electric shock	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0004 affected630 at risk EG0013 affected631 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Fractured ischium	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Joint sprain	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Ligament injury	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Muscle injury	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0012 affected631 at risk
Scapula fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0012 affected631 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Colonoscopy	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0010 affected631 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0013 affected631 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected630 at risk EG0012 affected631 at risk
Osteolysis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Spinal column stenosis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Bile duct cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Hepatic neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Leiomyosarcoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Non-small cell lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0010 affected631 at risk
Ovarian adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0012 affected631 at risk
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0012 affected631 at risk
Cerebrovascular disorder	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Cranial nerve paralysis	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Dizziness	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Embolic stroke	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0010 affected631 at risk
Loss of consciousness	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Syncope	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Alcohol abuse	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Depression	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Mental disorder due to a general medical condition	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Suicide attempt	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Glomerulonephritis	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Haematuria	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0012 affected631 at risk
Renal colic	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected630 at risk EG0010 affected631 at risk
Renal failure chronic	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Penile pain	Reproductive system and breast disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0011 affected631 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Organising pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Ureteral catheterisation	Surgical and medical procedures	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Embolism	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Extremity necrosis	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Hypertensive crisis	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected630 at risk EG0010 affected631 at risk
Hypotension	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Intermittent claudication	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Lymphoedema	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected630 at risk EG0011 affected631 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected630 at risk EG0010 affected631 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00030 affected630 at risk EG00133 affected631 at risk
Influenza	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG00033 affected630 at risk EG00126 affected631 at risk
Nasopharyngitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG00062 affected630 at risk EG00171 affected631 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG00043 affected630 at risk EG00130 affected631 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG000112 affected630 at risk EG00190 affected631 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG000197 affected630 at risk EG001191 affected631 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG00030 affected630 at risk EG00134 affected631 at risk
Dizziness	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG00030 affected630 at risk EG00133 affected631 at risk
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG00027 affected630 at risk EG00135 affected631 at risk
Hypertension	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG00035 affected630 at risk EG00130 affected631 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D011799	Quinazolines