To Assess The Efficacy and Safety Of Oral Sildenafil in t... | NCT00430716

ID	Type	Description	Link
2006-006748-76	EudraCT Number

Label	Type	Description	Intervention Names
Sildenafil High dose	Experimental		Drug: Sildenafil citrate
Sildenafil Low dose	Experimental		Drug: Sildenafil citrate
Sildenafil medium dose	Experimental		Drug: Sildenafil citrate
Sildenafil - Open label Phase	Experimental	Open label extension from week 12 to week 24.	Drug: Sildenafil citrate

Name	Type	Description	Arm Group Labels	Other Names
Sildenafil citrate	Drug	oral, 20 mg, tid	Sildenafil High dose
Sildenafil citrate

Measure	Description	Time Frame
Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12	6 MWT was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.	Baseline and Week 12

Measure	Description	Time Frame
Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12	mPAP was measured using a pressure transducer positioned at the mid-axillary line.	Baseline and Week 12
Number of Participants With Clinical Worsening

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

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Pulmonary Specialists, LTD		Phoenix	Arizona	85013	United States
Medical College of Georgia

PubMed Identifier	Type	Citation	Retractions
28228114	Derived	Vizza CD, Sastry BK, Safdar Z, Harnisch L, Gao X, Zhang M, Lamba M, Jing ZC. Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension. BMC Pulm Med. 2017 Feb 23;17(1):44. doi: 10.1186/s12890-017-0374-x.

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

ID	Title	Description
FG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
FG001

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 the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 12

6 MWT was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.

Intention to Treat (ITT population) included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, last observation carried forward (LOCF) method of imputation was used.

Posted

Mean

95% Confidence Interval

Meters

Baseline and Week 12

ID	Title	Description
OG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG002	Sildenafil 20 mg	Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).

Units	Counts
Participants	OG00041 OG00140 OG00242

Title

Denominators

Categories

Title	Measurements
	OG00014.21(0.41 to 28.00) OG00140.75(25.16 to 56.34) OG00238.36(23.77 to 52.94)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	An analysis of variance (ANOVA) model followed by the Williams trend test (one-sided, at the 2.5% level of significance) was used. The Williams trend test firstly determined if there was a significant downward trend in response for the descending doses, and then subsequently determined the highest dose that was statistically inferior to 20 mg (known to be an effective dose of sildenafil). A corresponding 97.5% lower confidence limit for the difference was presented.	ANOVA		0.011		Mean Difference (Net)	24.15			1-Sided	97.5	3.37						Superiority or Other (legacy)

Secondary

Change From Baseline in Mean Pulmonary Arterial Pressure (mPAP) at Week 12

mPAP was measured using a pressure transducer positioned at the mid-axillary line.

ITT population included all participants who were randomized to study treatment and received at least 1 dose of study medication. If participant had missing value at any visit, LOCF method of imputation was used.

Posted

Mean

95% Confidence Interval

mmHg

Baseline and Week 12

ID	Title	Description
OG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG002	Sildenafil 20 mg	Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).

Secondary

Number of Participants With Clinical Worsening

Clinical worsening was defined as death; or lung transplantation; or hospitalization due to pulmonary hypertension; or initiation of prostacyclin therapy; or initiation of endothelin receptor antagonist therapy. (PAH=pulmonary arterial hypertension) Due to very low number of events of clinical worsening reported, the median days to clinical worsening could not be estimated.

ITT population for clinical worsening included all participants who had been randomized to study treatment and received at least 1 dose of study medication.

Posted

Count of Participants

Participants

Baseline through Week 12

ID	Title	Description
OG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG002	Sildenafil 20 mg

Secondary

Number of Participants With Change From Baseline in PAH Criteria for Functional Capacity and Therapeutic Class at Week 12

Pulmonary arterial hypertension (PAH) Criteria for WHO Class: Class I (Participants without resulting limitation of physical activity);Class II (Participants with slight limitation of physical activity though comfortable at rest);Class III (Participants with marked limitation of physical activity,though comfortable at rest);Class IV(Participants with inability to carry out any physical activity without symptoms,manifest signs of right heart failure; dyspnoea and/or fatigue may even be present at rest; and discomfort is increased by any physical activity).

Posted

Number

Participants

Baseline and Week 12

ID	Title	Description
OG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.

Secondary

Change From Baseline in B-Type Natriuretic Peptide (BNP) at Week 12

BNP is a non-invasive biomarker and an indicator of progression of PAH/ right ventricular dysfunction in participants with PAH.

Posted

Mean

95% Confidence Interval

pg/mL

Baseline and Week 12

ID	Title	Description
OG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG002	Sildenafil 20 mg	Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).

Secondary

Change From Baseline in Pro-BNP at Week 12

Pro- BNP which is a precursor of BNP, is a non-invasive biomarker and an indicator of progression of PAH / RV dysfunction in participants with PAH.

Posted

Mean

95% Confidence Interval

pg/mL

Baseline and Week 12

ID	Title	Description
OG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG002	Sildenafil 20 mg	Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).

Secondary

Change From Baseline in TAPSE Measurement at Week 12

Tricuspid annular plane systolic excursion (TAPSE) was measured as the total displacement of the tricuspid annulus in cm from end diastole to end systole.TAPSE is an indicator of progression of PAH /right ventricular dysfunction.

The baseline data for 33 participants were measured incorrectly and the results from the 33 participants (both baseline and post-baseline) were excluded from the analysis.

Posted

Mean

95% Confidence Interval

Baseline and Week 12

ID	Title	Description
OG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG002

Secondary

Change From Baseline in BORG Dyspnoea Score at Week 12

BORG dyspnoea scale is a 10-point scale where following scores stands for severity of dyspnoea: 0 (no breathlessness at all); 0.5 (very very slight [just noticeable]); 1 (very slight); 2 (slight breathlessness); 3 (moderate); 4 (some what severe); 5 (severe breathlessness); 7 (very severe breathlessness); 9 (very very severe [almost maximum] and 10 (maximum).

Posted

Mean

95% Confidence Interval

Units on a scale

Baseline and Week 12

ID	Title	Description
OG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
OG002	Sildenafil 20 mg

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0022 affected45 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Cyanosis	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Right ventricular failure	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Tachycardia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Hereditary haemorrhagic telangiectasia	Congenital, familial and genetic disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Conjunctivitis	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Periorbital oedema	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Photophobia	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Vision blurred	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0012 affected43 at risk EG0021 affected45 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Flatulence	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Asthenia	General disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Exercise tolerance decreased	General disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Fatigue	General disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0002 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Feeling hot	General disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Medical device pain	General disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Oedema peripheral	General disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0022 affected45 at risk
Pyrexia	General disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Bronchitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Conjunctivitis bacterial	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Herpes zoster	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0002 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Otitis externa	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Rhinitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Sinusitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Tinea barbae	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Blood potassium decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Prostatic specific antigen increased	Investigations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Weight decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Weight increased	Investigations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
White blood cell count decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0022 affected45 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0022 affected45 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Dizziness	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0002 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Dysgeusia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Headache	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0023 affected45 at risk
Lethargy	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Loss of consciousness	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Paraesthesia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Presyncope	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Sciatica	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Anxiety	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Depression	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Insomnia	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Micturition urgency	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Renal failure	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0002 affected41 at risk EG0013 affected43 at risk EG0023 affected45 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0012 affected43 at risk EG0020 affected45 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Orthopnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Upper airway obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Lichen planus	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0022 affected45 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Flushing	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0012 affected43 at risk EG0021 affected45 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	Double Blind Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0022 affected45 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Angina pectoris	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Cyanosis	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Right ventricular failure	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Tachycardia	Cardiac disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Hereditary haemorrhagic telangiectasia	Congenital, familial and genetic disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Goitre	Endocrine disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Blindness transient	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Conjunctivitis	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Periorbital oedema	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Photophobia	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Vision blurred	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Visual impairment	Eye disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0012 affected43 at risk EG0021 affected45 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Faecal incontinence	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Flatulence	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Gingival bleeding	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Glossodynia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Asthenia	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0012 affected43 at risk EG0022 affected45 at risk
Chest pain	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0012 affected43 at risk EG0020 affected45 at risk
Exercise tolerance decreased	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Fatigue	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0003 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Feeling hot	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Medical device pain	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Oedema	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Oedema peripheral	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0022 affected45 at risk
Pyrexia	General disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0002 affected41 at risk EG0012 affected43 at risk EG0020 affected45 at risk
Bronchitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Conjunctivitis bacterial	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Gastroenteritis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Herpes zoster	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Infected bites	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Influenza	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0002 affected41 at risk EG0011 affected43 at risk EG0023 affected45 at risk
Otitis externa	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Rhinitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Sinusitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Tinea barbae	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0012 affected43 at risk EG0021 affected45 at risk
Blood potassium decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0002 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Blood pressure increased	Investigations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Blood urea increased	Investigations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Prostatic specific antigen increased	Investigations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Weight decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0012 affected43 at risk EG0020 affected45 at risk
Weight increased	Investigations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
White blood cell count decreased	Investigations	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0023 affected45 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0002 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0022 affected45 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0022 affected45 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0002 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Dizziness	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0003 affected41 at risk EG0012 affected43 at risk EG0022 affected45 at risk
Dysgeusia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Head discomfort	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Headache	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0002 affected41 at risk EG0013 affected43 at risk EG0023 affected45 at risk
Lethargy	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0021 affected45 at risk
Loss of consciousness	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Paraesthesia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Presyncope	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0012 affected43 at risk EG0020 affected45 at risk
Sciatica	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Syncope	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Anxiety	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Depression	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Insomnia	Psychiatric disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Micturition urgency	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Renal failure	Renal and urinary disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0002 affected41 at risk EG0014 affected43 at risk EG0023 affected45 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0013 affected43 at risk EG0020 affected45 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Orthopnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Upper airway obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Butterfly rash	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Increased tendency to bruise	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Lichen planus	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Palmar erythema	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0022 affected45 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0011 affected43 at risk EG0020 affected45 at risk
Flushing	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0012 affected43 at risk EG0021 affected45 at risk
Hypertension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0020 affected45 at risk
Hypotension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0001 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	Open Label Phase	EG0000 affected41 at risk EG0010 affected43 at risk EG0021 affected45 at risk

ID	Term
D006976	Hypertension, Pulmonary
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D013450	Sulfones
D013457	Sulfur Compounds
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description
BG000	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
BG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.
BG002	Sildenafil 20 mg	Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).
BG003	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	Sildenafil 1 mg	Sildenafil 1 milligram (mg) tablet taken orally 3 times a day (TID) for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.	1	41	6	41	21	41
EG001	Sildenafil 5 mg	Sildenafil 5 mg tablet taken orally TID for first 12 weeks (double blind treatment phase of the study) and placebo matched to 20 mg. For a further 12 weeks (open label extension phase), participants received sildenafil 20 mg tablets TID.	1	43	3	43	22	43
EG002	Sildenafil 20 mg	Sildenafil 20 mg tablet taken orally TID throughout the study and placebo matched to 1 and 5 mg during first 12 weeks (double blind treatment phase).	0	45	5	45	22	45