A Study of the Effectiveness of Sitaxsentan Sodium in Pat... | NCT00303498

ID	Type	Description	Link
FDHF01	Other Identifier	Alias Study Number

Label	Type	Description	Intervention Names
Sitaxsentan sodium	Experimental		Drug: Sitexsentin sodium
Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Sitexsentin sodium	Drug	sitaxsentan 100 mg (target dose) 0rally once daily. A 10-week Run-In Phase was conducted where dosing commenced at 25 mg daily for 2 weeks, and then was stepped up to 50 mg daily for 2 weeks, to 75 mg daily for 2 weeks and then to 100 mg daily for 2 weeks, with an additional 2-week stabilization period (10 weeks total) to a target study dose of 100 mg daily. During the Run-In Phase, if a subject was not able to tolerate upward dose titration to the target dose of 100 mg, the investigator may have elected to continue at the current dosage or reduce the dosage of sitaxsentan or placebo to the subject's immediate prior dose. During the Maintenance Phase, subjects received the highest titrated dose reached of study drug and continued it through the last day of Week M24 of the Maintenance Phase (14 weeks)- total study drug treatment duration= 6 months

Measure	Description	Time Frame
Change From Baseline in Treadmill Exercise Time at Maintenance Phase Week 24	Treadmill exercise test is used to assess the functional capacity of participants with cardiac disease. Treadmill exercise test was conducted using the 2 minute incremental Naughton protocol. The Naughton protocol starts with a 2 minute warm-up. The speed of treadmill is set to 1 mile per hour (mph) and the incline is set to 0. After the warm-up, the speed is set at 2 mph for the remainder of the test. The test consists of six, 2 minute intervals. The grade starts at 0 for the first interval, and increases by 3.5 percent every 2 minutes. The change in total exercise time (in seconds) during the treadmill test was reported.	Baseline, Week 24 (Maintenance Phase)

Measure	Description	Time Frame
Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24	Ratio of E to E' is used as a predictor of first cardiac events. Ratio of E to E' was measured using imaging techniques based on Doppler principles. Transmitral inflow velocity was measured by Doppler echocardiography (ECHO) and the early diastolic velocity of the mitral annulus was measured by tissue Doppler imaging (TDI).

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294	United States
Mobile Heart Specialists, PC

PubMed Identifier	Type	Citation	Retractions
24720918	Derived	Zile MR, Bourge RC, Redfield MM, Zhou D, Baicu CF, Little WC. Randomized, double-blind, placebo-controlled study of sitaxsentan to improve impaired exercise tolerance in patients with heart failure and a preserved ejection fraction. JACC Heart Fail. 2014 Apr;2(2):123-30. doi: 10.1016/j.jchf.2013.12.002. Epub 2014 Feb 26.

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.

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 Treadmill Exercise Time at Maintenance Phase Week 24

Treadmill exercise test is used to assess the functional capacity of participants with cardiac disease. Treadmill exercise test was conducted using the 2 minute incremental Naughton protocol. The Naughton protocol starts with a 2 minute warm-up. The speed of treadmill is set to 1 mile per hour (mph) and the incline is set to 0. After the warm-up, the speed is set at 2 mph for the remainder of the test. The test consists of six, 2 minute intervals. The grade starts at 0 for the first interval, and increases by 3.5 percent every 2 minutes. The change in total exercise time (in seconds) during the treadmill test was reported.

Intent-to-treat (ITT) population was defined as all participants who received at least 1 dose of study drug and had at least 1 valid treadmill test value at baseline and post-baseline during maintenance phase. Last observation carried forward (LOCF) method was used to impute missing values.

Posted

Median

Full Range

Seconds

Baseline, Week 24 (Maintenance Phase)

ID	Title	Description
OG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.
OG001	Placebo	Participants received placebo matched to sitaxsentan orally once daily for 34 weeks (10-Week Run-In Phase and 24-Week Maintenance Phase).

Units	Counts
Participants	OG00096 OG00152

Title

Denominators

Categories

Baseline

Title	Measurements
	OG000424.5(121 to 706) OG001485.0(126 to 693)

Change at Week 24

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The median of the treatment difference was calculated using the Hodges-Lehmann estimator.	ANCOVA	Change at Week 24: P-value was obtained from the non-parametric analysis of covariance (ANCOVA) controlling for baseline treadmill exercise time.	0.0302		Median Difference (Net)	43.0											Superiority or Other (legacy)

Secondary

Change From Baseline in Ratio of Transmitral Inflow Velocity (E) to Early Diastolic Velocity of the Mitral Annulus (E') at Maintenance Phase Week 24

Ratio of E to E' is used as a predictor of first cardiac events. Ratio of E to E' was measured using imaging techniques based on Doppler principles. Transmitral inflow velocity was measured by Doppler echocardiography (ECHO) and the early diastolic velocity of the mitral annulus was measured by tissue Doppler imaging (TDI).

ITT population was defined as all the participants who received at least 1 dose of study drug and had at least 1 valid treadmill test value at baseline and post-baseline during maintenance phase. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure and 'Number Analyzed' signifies the participants who were evaluable at the specified time points for each group, respectively.

Posted

Mean

Standard Deviation

Ratio

Baseline, Week 24 (Maintenance Phase)

ID	Title	Description
OG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.

Secondary

Change From Baseline in Left Ventricular Mass at Maintenance Phase Week 24

Left ventricular mass was used as a parameter for the assessment of cardiac function. An increase in left ventricular mass leads to ventricular hypertrophy which is a prognostic factor of cardiovascular morbidity and mortality. Left ventricular mass was measured by ECHO, which was calculated as (1.04 * [{left ventricular end diastolic diameter (LVEDD) + septal diastolic thickness + post wall diastolic thickness}^3 - LVEDD^3]) * 0.8 + 0.6. Left ventricular mass was assessed for the two ECHO modes: parasternal long-axis two dimensional (PLAX 2D) mode and parasternal short-axis view motion (PSAX M) mode.

ITT population defined as all participants who received at least 1 dose of study drug and had at least 1 valid treadmill test value at baseline and post-baseline during maintenance phase. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure and 'Number Analyzed' signifies the participants who were evaluable at the specified time points for each group, respectively.

Posted

Mean

Standard Deviation

Centimeter^3

Baseline, Week 24 (Maintenance Phase)

ID	Title	Description
OG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.

Secondary

Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Total Score at Maintenance Phase Week 24

The MLHF is a 21-item questionnaire which used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL total score was calculated as the sum of the 21 individual QoL questions. The MLHF QoL total score ranged from 0 to 105, where higher scores indicated worse health condition.

ITT population. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure. LOCF method was used to impute missing values.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Week 24 (Maintenance Phase)

ID	Title	Description
OG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.

Secondary

Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Physical Score at Maintenance Phase Week 24

The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL physical score was calculated as the sum of the 8 physical domain QoL questions. The MLHF QoL physical score ranged from 0 to 40, where higher scores indicated worse health condition.

ITT population. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure. LOCF method was used to impute missing values.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Week 24 (Maintenance Phase)

ID	Title	Description
OG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.

Secondary

Change From Baseline in Minnesota Living With Heart Failure (MLHF) Questionnaire - Quality of Life (QoL) Emotional Score at Maintenance Phase Week 24

The MLHF is a 21-item questionnaire which is used to evaluate QoL in participants suffering from heart failure. The participants were asked to evaluate how their heart condition affected their life during the past month. Each of the 21 items were assessed on a 6-point scale, where 0 = no affect and 5 = very much affected. The MLHF QoL emotional score was calculated as the sum of the 5 emotional domain QoL questions. The MLHF QoL emotional score ranged from 0 to 25, where higher scores indicated worse health condition.

ITT population. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure. LOCF method was used to impute missing values.

Posted

Mean

Standard Deviation

Units on a scale

Baseline, Week M24 (Maintenance Phase)

ID	Title	Description
OG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.

Secondary

Number of Participants With Change From Baseline in New York Heart Association (NYHA) Functional Class at Maintenance Phase Week 24

Participants were classified by NYHA functional class. NYHA class I: participants with cardiac disease but without resulting limitations of physical activity, NYHA class II: participants with cardiac disease resulting in slight limitation of physical activity, NYHA class III: participants with cardiac disease resulting in marked limitation of physical activity, NYHA class IV: participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. Baseline was reported by NYHA functional class and the change from baseline in the functional class was reported as improvement (positive change from baseline), no change and deterioration (negative change from baseline).

ITT population. LOCF method was used to impute missing values.

Posted

Count of Participants

Participants

Baseline, Week 24 (Maintenance Phase)

ID	Title	Description
OG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0007 affected127 at risk EG0011 affected64 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Angina pectoris	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0013 affected64 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Bundle branch block right	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Cardiac failure	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Cardiac flutter	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Coronary artery disease	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Cyanosis	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Low cardiac output syndrome	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Palpitations	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0006 affected127 at risk EG0018 affected64 at risk
Pulmonary valve disease	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Tachycardia	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Thyroid cyst	Endocrine disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Blindness transient	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Eye allergy	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Eye haemorrhage	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Eye irritation	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Glaucoma	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Lacrimation increased	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Posterior capsule rupture	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Vision blurred	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Abdominal hernia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0011 affected64 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0011 affected64 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0010 affected64 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0015 affected64 at risk
Dental caries	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0006 affected127 at risk EG0012 affected64 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0014 affected64 at risk
Flatulence	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Gastritis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0010 affected64 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00010 affected127 at risk EG0014 affected64 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Rectal fissure	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Toothache	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0005 affected127 at risk EG0013 affected64 at risk
Adverse drug reaction	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Asthenia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Chest discomfort	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected127 at risk EG0011 affected64 at risk
Chest pain	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0007 affected127 at risk EG0014 affected64 at risk
Chills	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Fatigue	General disorders	MedDRA 18.1	Non-systematic Assessment	EG00010 affected127 at risk EG0014 affected64 at risk
Ill-defined disorder	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Malaise	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Non-cardiac chest pain	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0012 affected64 at risk
Oedema	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Oedema peripheral	General disorders	MedDRA 18.1	Non-systematic Assessment	EG00020 affected127 at risk EG0018 affected64 at risk
Pain	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0010 affected64 at risk
Peripheral swelling	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0012 affected64 at risk
Pyrexia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Swelling	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Thirst	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Hypersensitivity	Immune system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Seasonal allergy	Immune system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Acarodermatitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Atypical pneumonia	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Bronchitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0011 affected64 at risk
Cellulitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Diverticulitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Ear infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Fungal infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Fungal skin infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0011 affected64 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Hepatitis C	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Herpes virus infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Influenza	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0004 affected127 at risk EG0012 affected64 at risk
Kidney infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Localised infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Nail infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0006 affected127 at risk EG0014 affected64 at risk
Oral herpes	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Pneumonia	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Sinusitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0005 affected127 at risk EG0012 affected64 at risk
Tooth abscess	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Tooth infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00013 affected127 at risk EG0013 affected64 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG00012 affected127 at risk EG0015 affected64 at risk
Wound infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0012 affected64 at risk
Eschar	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Muscle injury	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Alanine aminotransferase increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Blood bilirubin increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Blood creatinine increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0012 affected64 at risk
Blood glucose abnormal	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Blood glucose fluctuation	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Blood glucose increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Blood potassium increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Blood pressure increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Blood pressure orthostatic increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Clostridium test	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Electrocardiogram T wave abnormal	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Eosinophil count increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0010 affected64 at risk
Glycosylated haemoglobin increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Haematocrit decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Haemoglobin decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0012 affected64 at risk
Heart rate decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Heart rate increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Helicobacter test positive	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Liver function test abnormal	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Neutrophil count decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Occult blood positive	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0012 affected64 at risk
Pedal pulse decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Platelet count decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Red cell distribution width increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Renal function test abnormal	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Reticulocyte count increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Weight increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0014 affected64 at risk
White blood cell count increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0010 affected64 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected127 at risk EG0011 affected64 at risk
Gout	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0012 affected64 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0006 affected127 at risk EG0016 affected64 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0010 affected64 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0008 affected127 at risk EG0014 affected64 at risk
Fibromyalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Muscle fatigue	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected127 at risk EG0015 affected64 at risk
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0010 affected64 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0012 affected64 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0009 affected127 at risk EG0014 affected64 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Tendon disorder	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0011 affected64 at risk
Eyelid tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Haemangioma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Thyroid neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Amnesia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Balance disorder	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Cerebrovascular disorder	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Diabetic neuropathy	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Dizziness	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG00010 affected127 at risk EG0016 affected64 at risk
Dysgeusia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Headache	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0009 affected127 at risk EG00111 affected64 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Lethargy	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Migraine	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Myoclonus	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Paraesthesia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0012 affected64 at risk
Poor quality sleep	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Presyncope	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Sciatica	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Somnolence	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0012 affected64 at risk
Syncope	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0013 affected64 at risk
Tremor	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Anxiety	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0013 affected64 at risk
Depression	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0012 affected64 at risk
Dissociative fugue	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Euphoric mood	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Insomnia	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0014 affected64 at risk
Nightmare	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Sleep disorder	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0012 affected64 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Micturition urgency	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Renal failure	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Urine odour abnormal	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Breast enlargement	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Breast haemorrhage	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Breast mass	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Breast tenderness	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Cystocele	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0009 affected127 at risk EG0012 affected64 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG00018 affected127 at risk EG0018 affected64 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0010 affected64 at risk
Dyspnoea paroxysmal nocturnal	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected127 at risk EG0010 affected64 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0012 affected64 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected127 at risk EG0010 affected64 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0011 affected64 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0010 affected64 at risk
Angina unstable	Cardiac disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0012 affected64 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected127 at risk EG0011 affected64 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0003 affected127 at risk EG0014 affected64 at risk
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Cataract operation	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Lung operation	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Oral surgery	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Sinus operation	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Synovectomy	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Toe operation	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Uterine dilation and curettage	Surgical and medical procedures	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Flushing	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Hot flush	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0013 affected64 at risk
Hypertension	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0004 affected127 at risk EG0013 affected64 at risk
Hypotension	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0008 affected127 at risk EG0012 affected64 at risk
Lymphoedema	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected127 at risk EG0010 affected64 at risk
Phlebitis	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected127 at risk EG0011 affected64 at risk

ID	Term
D006333	Heart Failure
D006331	Heart Diseases
D002318	Cardiovascular Diseases

ID	Title	Description
BG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.
BG001	Placebo	Participants received placebo matched to sitaxsentan orally once daily for 34 weeks (10-Week Run-In Phase and 24-Week Maintenance Phase).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sitaxsentan	During the Run-In Phase, participants received sitaxsentan 25 milligram (mg) dose orally once daily for 2 weeks (Week 1 and Week 2). The dose was then up-titrated to 50 mg for the next 2 weeks (Week 3 and Week 4), and then to 75 mg for following 2 weeks (Week 5 and Week 6). The dose was finally up-titrated to the target study dose of 100 mg for the next 2 weeks (Week 7 and Week 8), with an additional 2-week stabilization period (up to Week 10). If a participant was unable to tolerate the upward dose titration to the target dose of 100 mg, the participant continued at the last titrated dose for the remainder of the Run-In Phase. During the Maintenance Phase, participants continued to receive the target dose of 100 mg or the maximum up-titrated Run-In Phase dose for 24 weeks.			25	127	107	127
EG001	Placebo	Participants received placebo matched to sitaxsentan orally once daily for 34 weeks (10-Week Run-In Phase and 24-Week Maintenance Phase).			16	64	54	64