A Randomized, Double-Blind, Placebo-Controlled Study of S... | NCT00159913

NCT00159913

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Sildenafil Low dose	Experimental	Drug: Sildenafil citrate
Sildenafil Medium dose	Experimental	Drug: Sildenafil citrate
Sildenafil High dose	Experimental	Drug: Sildenafil citrate
Placebo	Placebo Comparator	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Sildenafil citrate	Drug	oral; 20mg, 40mg and 80 mg; 3 times a day(TID)	Sildenafil High dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Intent To Treat Population	Peak VO2 (normalized for body weight) at trough plasma levels assessed by CPX testing (bicycle ergometry)at the end of treatment (Week 16 for those who completed the study). Mean Percent change = [(week 16 value minus baseline mean)/mean at baseline]*100%.	Baseline, Week 16
Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Per Protocol Population	Peak VO2 (normalized for body weight) at trough plasma levels assessed by CPX testing (bicycle ergometry)at the end of treatment (Week 16 for those who completed the study). Mean Percent change = [(week 16 value minus baseline mean)/mean at baseline]*100%.	Baseline, Week 16

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 16 in Mean Pulmonary Artery Pressure (mPAP)	mPAP, a hemodynamic parameter, was measured using a pressure transducer positioned at the mid-axillary line with the patient in the supine position. Change is observed value at Week 16 minus Baseline value.	Baseline, Week 16
Change From Baseline to Week 16 in Pulmonary Vascular Resistance Index (PVRI)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female subjects aged from 1 to 17 years old and weighing >= 8 kg with a mean pulmonary artery pressure >= 25 mmHg at rest, PCWP <= 15 mmHg, and PVRI >= 3 Wood units x m2 (if PCWP is not available, then mean LA pressure <= 15 mmHg or LVEDP <= 15 mmHg in the absence of left atrial obstruction).
Females of child bearing potential who were sexually active must have been practicing a suitable method of birth control so that in the opinion of the investigator, they would not become pregnant during the study.
Subjects who have symptomatic pulmonary arterial hypertension due to: primary pulmonary hypertension; pulmonary arterial hypertension in the presence of a small or hemodynamically insignificant congenital systemic to pulmonary shunt lesion that in the opinion of the investigator is not the cause of pulmonary hypertension; collagen vascular disease; congenital systemic-to-pulmonary shunts with a baseline resting room air oxygen saturation >= 88% unrepaired or repaired at least 6 months prior to screening; d-transposition of the great arteries repaired within the first 30 days of life; or surgical repair of other congenital heart lesions at least 6 months prior to screening and do not have clinically significant residual left-sided heart disease consistent with the exclusion criteria.
Subjects, developmentally able to exercise, whose CPX exercise test functional capacity is within the following parameters: Peak VO2 >= 10 mL/kg/min and <= 28 mL/kg/min during screening CPX test;
Written informed consent and assent where applicable before the subject is screened for the study.
Subjects who undergo a large shift in altitude (defined as approximately 5000 feet or 1524 meters) in order to participate in the study must reside at the "in study" altitude for at least 90 days prior to baseline and during the study period.

Exclusion Criteria:

Subjects with pulmonary hypertension secondary to sickle cell disease, any other disease known to be associated with PAH, or any etiology other than those specified in the inclusion criteria.
Left-sided heart disease, including aortic or mitral valve disease (greater than mild), restrictive or congestive cardiomyopathy; PCWP or LVEDP > 15 mmHg; LVEF < 40% determined by MUGA, angiography or echocardiography; LV shortening fraction < 22% determined by echocardiography, symptomatic coronary disease (demonstrable ischemia).
Pericardial constriction; significant (2+ for regurgitation) valvular disease other than tricuspid or pulmonary regurgitation; acutely decompensated heart failure within previous 30 days from screening; atrial septostomy within previous 6 months of screening;
Hemodynamic instability or hypo- or hypertension at screening, i.e., SBP outside of 70-140 mmHg.
A history of stroke, myocardial infarction or life threatening arrhythmia within 6 months of screening.
Moderate to severe restrictive pulmonary disease (Total Lung Capacity or Forced Vital Capacity <= 60% of normal) or history of severe lung disease.
Subjects with bronchopulmonary dysplasia (BPD) and other chronic lung diseases.
History of pulmonary embolism.
Subjects whose CPX test is limited by conditions other than pulmonary hypertension-associated dyspnea or fatigue.
Subjects who are known to be HIV positive
Subjects with impairment of renal function (serum creatinine > 2.5x ULN ) or hepatic function (ALT and/or AST > 3x ULN; and/or bilirubin >= 2 mg/dL). Hematological abnormalities (e.g., severe anemia, Hgb < 10 g/dL, leukopenia, WBC < 2500/mL).
Subjects who previously received bosentan and whose liver function tests taken at screening are > 2x ULN.
Subjects with any medical condition which in the opinion of the investigator may interfere with treatment, evaluation of safety, and/or efficacy.
Change in class of medication for CHF or PAH within the 10 days prior to qualifying right heart catheterization.
Subjects who are currently prescribed and/or taking nitrates or nitric oxide donors in any form. Acute vasodilator testing with nitric oxide is permitted during hemodynamic evaluation; taking chronic arginine supplementation including Heart Bar; therapy involving parenteral inotropic medication or parenteral vasodilators within 3 months of screening; current therapy with alpha-blockers, potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole and protease inhibitors), Ritonavir or Nicorandil; chronic treatment with off-label sildenafil, an endothelin antagonist or prostacyclin/prostacyclin analogue within 30 days of randomization.
Pregnant or lactating female.
Any medical or psychological condition or social circumstances that would impair their ability to participate reliably in the study or who were not likely to complete the study for any reason; current or past illicit drug use or alcoholism excepting if abstinence can be documented for >= 1 year.
Participation in another clinical trial of an investigational drug or device (including placebo) within 30 days of screening for entry into the present study.
Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic anterior ischemic optic neuropathy (NAION).

Contacts/Locations Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Palo Alto	California	94304	United States
Pfizer Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31908813	Derived	Russell S, Beghetti M, Oudiz R, Balagtas C, Zhang M, Ivy D. Effects of oral sildenafil on exercise capacity in children with pulmonary arterial hypertension: a randomised trial. Open Heart. 2019 Dec 3;6(2):e001149. doi: 10.1136/openhrt-2019-001149. eCollection 2019.
31538282	Derived	Chanu P, Gao X, Bruno R, Claret L, Harnisch L. A modeling and simulation-based assessment of the impact of confounding factors on the readout of a sildenafil survival trial in pulmonary arterial hypertension. J Pharmacokinet Pharmacodyn. 2019 Oct;46(5):499-509. doi: 10.1007/s10928-019-09654-3. Epub 2019 Sep 20.

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

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
BG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
BG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
BG003	Placebo	Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Number

participants

Title

Denominators

Categories

Title	Measurements
	OG0006.44± 20.16(-6.11 to 13.73) OG00113.40± 19.50(1.72 to 20.94) OG00210.58± 15.51(-1.64 to 17.60)

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
OG003 OG004		ANCOVA	Analyses performed using analysis of covariance with etiology, weight and baseline peak VO2 as the covariates.	0.056	No adjustments for multiple comparisons have been made.	Mean Difference (Net)	7.71	Standard Error of the Mean	3.98		95	-0.19	15.60					Superiority or Other (legacy)
OG000

Secondary

Change From Baseline to Week 16 in Mean Pulmonary Artery Pressure (mPAP)

mPAP, a hemodynamic parameter, was measured using a pressure transducer positioned at the mid-axillary line with the patient in the supine position. Change is observed value at Week 16 minus Baseline value.

ITT population, using a LOCF (end-of-treatment) approach for handling missing data.

Posted

Mean

Standard Deviation

mm Hg

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Secondary

Change From Baseline to Week 16 in Pulmonary Vascular Resistance Index (PVRI)

PVRI equals Pulmonary Vascular Resistance (PVR) times Body Surface Area (BSA). Wood unit = 80dyn•s/cm5. Change is observed value at Week 16 minus Baseline value.

ITT population, LOCF

Posted

Mean

Standard Deviation

wood units. m2

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Secondary

Percent Change From Baseline to Week 16 in: Respiratory Exchange Ratio (RER)

RER is the ratio of carbon dioxide produced to oxygen consumed [VCO2/VO2]). Percent change is [(Week 16 value minus Baseline value)/Baseline value] * 100%

ITT population, LOCF (end-of-treatment) approach for handling missing values.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Secondary

Percent Change From Baseline to Week 16 in Time to Maximum Volume of Oxygen Consumed (VO2)

Time to maximum VO2 was assessed on the subset of subjects who are developmentally able to perform the exercise test. Percent change is [(value at Week 16 minus Baseline value)/Baseline value] * 100%

ITT population, LOCF (end-of-treatment) approach for handling missing values.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Secondary

Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR)

Change calculated as (mean PAP - PCWP)/COpulm in PVR is observed value at Week 16 minus Baseline value.

ITT population, using LOCF (end of treatment) approach for handling missing data

Posted

Mean

Standard Deviation

wood units

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Secondary

Change From Baseline to Week 16 in Cardiac Index (CI)

CI is observed value at Week 16 minus Baseline value. Calculated as cardiac output in systemic circulation (COsys) / body surface area (BSA).

ITT population, using LOCF (end of treatment) approach for handling missing data.

Posted

Mean

Standard Deviation

liters/minute/meters squared

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Secondary

Change From Baseline to Week 16 in Right Atrial Pressure (RAP)

RAP was measured using a pressure transducer positioned at the mid-axillary line with the patient in the supine position. Change is observed value at Week 16 minus Baseline value.

ITT population, using LOCF (end of treatment) approach for missing data.

Posted

Mean

Standard Deviation

mm Hg

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Secondary

Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Physical Scale

CHQ-PF28: validated generic Quality of Life (QoL) questionnaire for subjects >= 5 years. Includes 12 domain scores of QoL concepts including physical functioning, social & school activities, mental health, parent/family concepts. Scores range 0-100: lower scores = lower QoL. Change is observed value at Week 16 minus Baseline value.

ITT population, includes subjects >= 5 years with a valid questionnaire available in the subject's first language.

Posted

Mean

Standard Deviation

score on scale

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose

Secondary

Change From Baseline to Week 16 in Child Health Questionnaire Parent Form (CHQ-PF28), Psychosocial Scales

ITT population, includes subjects >= 5years with a valid questionnaire available in the subject's first language.

Posted

Mean

Standard Deviation

score on scale

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose

Secondary

Change From Baseline to Week 16 in World Health Organization (WHO) Pulmonary Hypertension (PH) Functional Class

WHO PH functional class definitions adapted from New York Heart Association Criteria for Functional Capacity and Therapeutic Class Definitions. Class I = PH without resulting limitation of physical activity, Class II = PH resulting in slight limitation of physical activity, Class III = PH resulting in marked limitation of physical activity, Class IV = PH with inability to carry out any physical activity without symptoms. Improved by 1 class = Class 4 to 3, Class 3 to 2, Class 2 to 1. Improved by 2 classes = Class 4 to 2, Class 3 to 1. Change is observed value at Week 16 minus Baseline value.

ITT population, LOCF

Posted

Number

units

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Primary

Percent Change From Baseline in Peak Volume of Oxygen (VO2) Consumed : Per Protocol Population

Per Protocol Population

Posted

Mean

Standard Deviation

percent change

Baseline, Week 16

ID	Title	Description
OG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.
OG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112
OG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Other Events (Affected)
EG000	Sildenafil Low Dose	Day 1-7 10 mg, followed by 10 mg TID (3 times daily) for body weights > 20-45 kg and > 45 kg, through Day 112. Modeling of the plasma concentrations for each dose level showed that the low and medium doses were predicted to be similar for the 8 to 20 kg subjects (ie, subjects would receive the same dose because of the available tablet strengths); consequently there was no low dose for the >= 8-20 kg weight group.	1	22
EG001	Sildenafil Medium Dose	Day 1-7 10 mg, followed by 10, 20, 40 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112	1	37
EG002	Sildenafil High Dose	Day 1-7 10 mg, followed by 20, 40, 80 mg TID (3 times daily) for body weights >= 8-20 kg, > 20-45 kg, > 45 kg respectively, through Day 112	7	44
EG003	Combined Sildenafil	This includes all subjects in the low, medium and high dose groups.	9	102
EG004	Placebo	Subjects randomized to this arm recieved placebo TID (three times daily) for 112 days.	2	29

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bradycardia	Cardiac disorders	MedDRA 11.1	Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0021 affected77 at risk EG0031 affected174 at risk EG0040 affected60 at risk
Cardiac failure congestive	Cardiac disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0021 affected77 at risk EG003
Cyanosis	Cardiac disorders		Systematic Assessment	EG0001 affected42 at risk EG0010 affected55 at risk EG0020 affected77 at risk EG003
Ventricular arrhythmia	Cardiac disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0021 affected77 at risk EG003
Diarrhoea	Gastrointestinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0020 affected77 at risk EG003
Haematochezia	Gastrointestinal disorders		Systematic Assessment	EG0001 affected42 at risk EG0010 affected55 at risk EG0020 affected77 at risk EG003
Pyrexia	General disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0021 affected77 at risk EG003
Gastroenteritis	Infections and infestations		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0021 affected77 at risk EG003
Pneumonia	Infections and infestations		Systematic Assessment	EG0000 affected42 at risk EG0011 affected55 at risk EG0022 affected77 at risk EG003
Pneumonia bacterial	Infections and infestations		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0020 affected77 at risk EG003
Upper respiratory tract infection	Infections and infestations		Systematic Assessment	EG0000 affected42 at risk EG0011 affected55 at risk EG0021 affected77 at risk EG003
Syncope	Nervous system disorders		Systematic Assessment	EG0001 affected42 at risk EG0010 affected55 at risk EG0020 affected77 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0021 affected77 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders		Systematic Assessment	EG0001 affected42 at risk EG0010 affected55 at risk EG0020 affected77 at risk EG003
Stridor	Respiratory, thoracic and mediastinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0021 affected77 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 11.1	Systematic Assessment	EG0000 affected42 at risk EG0012 affected55 at risk EG0020 affected77 at risk EG0032 affected174 at risk EG0041 affected60 at risk
Conjunctivitis	Eye disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0022 affected77 at risk EG003
Abdominal pain	Gastrointestinal disorders		Systematic Assessment	EG0001 affected42 at risk EG0010 affected55 at risk EG0022 affected77 at risk EG003
Abdominal pain lower	Gastrointestinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0023 affected77 at risk EG003
Abdominal pain upper	Gastrointestinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0013 affected55 at risk EG0023 affected77 at risk EG003
Diarrhoea	Gastrointestinal disorders		Systematic Assessment	EG0002 affected42 at risk EG0013 affected55 at risk EG0027 affected77 at risk EG003
Dyspepsia	Gastrointestinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0012 affected55 at risk EG0020 affected77 at risk EG003
Nausea	Gastrointestinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0014 affected55 at risk EG0024 affected77 at risk EG003
Vomiting	Gastrointestinal disorders		Systematic Assessment	EG0003 affected42 at risk EG0015 affected55 at risk EG00211 affected77 at risk EG003
Chest pain	General disorders		Systematic Assessment	EG0002 affected42 at risk EG0011 affected55 at risk EG0022 affected77 at risk EG003
Fatigue	General disorders		Systematic Assessment	EG0002 affected42 at risk EG0010 affected55 at risk EG0022 affected77 at risk EG003
Bronchitis	Infections and infestations		Systematic Assessment	EG0002 affected42 at risk EG0015 affected55 at risk EG0023 affected77 at risk EG003
Influenza	Infections and infestations		Systematic Assessment	EG0000 affected42 at risk EG0012 affected55 at risk EG0020 affected77 at risk EG003
Laryngitis	Infections and infestations		Systematic Assessment	EG0001 affected42 at risk EG0010 affected55 at risk EG0021 affected77 at risk EG003
Nasopharyngitis	Infections and infestations		Systematic Assessment	EG0003 affected42 at risk EG0013 affected55 at risk EG0022 affected77 at risk EG003
Pharyngitis	Infections and infestations		Systematic Assessment	EG0003 affected42 at risk EG0013 affected55 at risk EG0021 affected77 at risk EG003
Pneumonia	Infections and infestations		Systematic Assessment	EG0000 affected42 at risk EG0012 affected55 at risk EG0020 affected77 at risk EG003
Rhinitis	Infections and infestations		Systematic Assessment	EG0001 affected42 at risk EG0013 affected55 at risk EG0021 affected77 at risk EG003
Upper respiratory tract infection	Infections and infestations		Systematic Assessment	EG0004 affected42 at risk EG0018 affected55 at risk EG0026 affected77 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders		Systematic Assessment	EG0002 affected42 at risk EG0010 affected55 at risk EG0020 affected77 at risk EG003
Dizziness	Nervous system disorders		Systematic Assessment	EG0002 affected42 at risk EG0012 affected55 at risk EG0022 affected77 at risk EG003
Headache	Nervous system disorders		Systematic Assessment	EG0005 affected42 at risk EG0016 affected55 at risk EG00212 affected77 at risk EG003
Enuresis	Renal and urinary disorders		Systematic Assessment	EG0000 affected42 at risk EG0012 affected55 at risk EG0020 affected77 at risk EG003
Erection increased	Reproductive system and breast disorders		Systematic Assessment	EG0000 affected42 at risk EG0011 affected55 at risk EG0022 affected77 at risk EG003
Spontaneous penile erection	Reproductive system and breast disorders		Systematic Assessment	EG0000 affected42 at risk EG0012 affected55 at risk EG0021 affected77 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders		Systematic Assessment	EG0002 affected42 at risk EG0014 affected55 at risk EG0022 affected77 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders		Systematic Assessment	EG0001 affected42 at risk EG0012 affected55 at risk EG0023 affected77 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders		Systematic Assessment	EG0001 affected42 at risk EG0012 affected55 at risk EG0020 affected77 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0010 affected55 at risk EG0020 affected77 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders		Systematic Assessment	EG0000 affected42 at risk EG0014 affected55 at risk EG0022 affected77 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders		Systematic Assessment	EG0000 affected42 at risk EG0012 affected55 at risk EG0021 affected77 at risk EG003
Flushing	Vascular disorders		Systematic Assessment	EG0001 affected42 at risk EG0011 affected55 at risk EG0020 affected77 at risk EG003
Pyrexia	General disorders		Systematic Assessment	EG0003 affected42 at risk EG0018 affected55 at risk EG0028 affected77 at risk EG003

ID	Term
D000081029	Pulmonary Arterial Hypertension

ID	Term
D000068677	Sildenafil Citrate

Ancestor Terms

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

EG0040 affected60 at risk

EG0041 affected60 at risk

EG0040 affected60 at risk

EG0041 affected60 at risk

EG0040 affected60 at risk

EG0042 affected60 at risk

EG0043 affected60 at risk

EG0040 affected60 at risk

EG0041 affected60 at risk

EG0044 affected60 at risk

EG0041 affected60 at risk

EG0040 affected60 at risk

EG0044 affected60 at risk

EG0042 affected60 at risk

EG0041 affected60 at risk

EG0040 affected60 at risk

EG0042 affected60 at risk

EG0044 affected60 at risk

EG0040 affected60 at risk

EG0041 affected60 at risk

EG0044 affected60 at risk

EG0042 affected60 at risk

EG0048 affected60 at risk

EG0040 affected60 at risk

EG0043 affected60 at risk

EG0042 affected60 at risk

EG0041 affected60 at risk

EG0042 affected60 at risk

EG0040 affected60 at risk

EG0043 affected60 at risk

EG0041 affected60 at risk

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