Trial Outcomes & Findings for Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension (NCT NCT01642407)

NCT ID: NCT01642407

Last Updated: 2021-02-01

Results Overview

WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 6 participants
• Primary outcome timeframe: Baseline, Week 4
• Results posted on: 2021-02-01

Participant Flow

The study was conducted at 3 sites in Japan. Data reported is based on data cut-off date of 26 December 2016.

Participant milestones

Measure	Sildenafil Participants received 10 milligram (mg) or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with less than or equal to (\<=) 20 kilogram (kg) of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with greater than (\>) 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Part 1 (Screening Till Week 16) STARTED	6
Part 1 (Screening Till Week 16) COMPLETED	3
Part 1 (Screening Till Week 16) NOT COMPLETED	3
Part 2(Week17 to Maximum of 119.6 Weeks) STARTED	3
Part 2(Week17 to Maximum of 119.6 Weeks) COMPLETED	1
Part 2(Week17 to Maximum of 119.6 Weeks) NOT COMPLETED	2

Reasons for withdrawal

Measure	Sildenafil Participants received 10 milligram (mg) or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with less than or equal to (\<=) 20 kilogram (kg) of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with greater than (\>) 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Part 1 (Screening Till Week 16) Insufficient clinical response	3
Part 2(Week17 to Maximum of 119.6 Weeks) Coil Embolization	1
Part 2(Week17 to Maximum of 119.6 Weeks) Change of treatment plan	1

Baseline Characteristics

Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Age, Categorical <=18 years	6 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	6.7 years STANDARD_DEVIATION 5.4 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points."

PVRI equals pulmonary vascular resistance (PVR) times body surface area (BSA) (PVRI = PVR*BSA). PVR is the resistance to blood flow through the pulmonary circulation and it was measured in Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5).

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) at Week 16 Baseline	18.567 wood units*meter^2 Standard Deviation 11.7629
Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) at Week 16 Change at Week 16	-4.113 wood units*meter^2 Standard Deviation 6.3770

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

It was a hemodynamic parameter and measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Week 16 Baseline	58.5 millimeter of mercury (mmHg) Standard Deviation 22.94
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) at Week 16 Change at Week 16	-6.5 millimeter of mercury (mmHg) Standard Deviation 15.15

PRIMARY outcome

Timeframe: Baseline, Week 4

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug.

WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 Baseline: Class I	2 participants 0.58
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 Baseline: Class II	3 participants 0.58
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 Baseline: Class III	1 participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 Baseline: Class IV	0 participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 Week 4: Improved	1 participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 Week 4: No change	5 participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 4 Week 4: Worsened	0 participants

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here,'N' (Overall number of participants analyzed) signifies those participants who were evaluable for this measure.

WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported.

Outcome measures

Measure	Sildenafil n=5 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 8 Improved	1 participants 0.71
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 8 No change	4 participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 8 Worsened	0 participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, Overall Number of participants analyzed signifies those participants who were evaluable for this measure.

WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported.

Outcome measures

Measure	Sildenafil n=4 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 16 Improved	1 participants 0.71
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 16 No change	3 participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Week 16 Worsened	0 participants

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

BNP is produced by ventricular cardiomyocytes. It causes reduction in preload and blood pressure by vasodilatation.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 16 Change at Week 16	-64.10 picogram per milliliter Standard Deviation 129.638
Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 16 Baseline	132.62 picogram per milliliter Standard Deviation 135.080

PRIMARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

NT pro-BNP is a cardiac marker, having the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 16 Baseline	843.03 picogram per milliliter Standard Deviation 1120.900
Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 16 Change at Week 16	-546.85 picogram per milliliter Standard Deviation 1107.621

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124

Population: Efficacy analysis set was used in this analysis. Here, 'Overall number of participants analyzed' specifies number of participants who completed Part 1 of the study and continued treatment with Sildenafil in Part 2 of the study and 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement = reduction in functional class, worsened = increase in functional class and no change = no change in functional class. Change from baseline in number of participants in each functional class were reported.

Outcome measures

Measure	Sildenafil n=3 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 100: Worsened	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 112: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Class I	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Class II	2 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Class III	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Class IV	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 28: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 28: No Change	2 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 28: Worsened	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 40: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 40: No Change	2 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 40: Worsened	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 52: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 52: No Change	2 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 52: Worsened	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 64: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 64: No Change	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 64: Worsened	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 76: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 76: No Change	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 76: Worsened	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 88: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 88: No Change	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 88: Worsened	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 100: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 100: No Change	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 112: No Change	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 112: Worsened	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 124: Improved	1 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 124: No Change	0 Participants
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With Pulmonary Arterial Hypertension (PAH) at Weeks 28, 40, 52, 64, 76, 88, 100, 112 and 124 Week 124:Worsened	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks)

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug.Here 'Overall number of participants analyzed' specifies number of participants who completed Part 1 of the study and continued treatment with Sildenafil in Part 2 of the study.

BNP is produced by ventricular cardiomyocytes. It causes reduction in preload and blood pressure by vasodilatation.

Outcome measures

Measure	Sildenafil n=3 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 52 and End of Treatment (EOT) Change at Week 52	-85.17 picograms per milliliter Standard Deviation 155.088
Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 52 and End of Treatment (EOT) Change at EoT	-85.17 picograms per milliliter Standard Deviation 155.088
Change From Baseline in Brain Natriuretic Peptide (BNP) at Week 52 and End of Treatment (EOT) Baseline	100.17 picograms per milliliter Standard Deviation 151.478

SECONDARY outcome

Timeframe: Baseline, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks)

Population: EEfficacy analysis set included all participants who received at least 1 dose of study drug.Here 'Overall number of participants analyzed' specifies number of participants who completed Part 1 of the study and continued treatment with Sildenafil in Part 2 of the study.

NT pro-BNP is a cardiac marker, having the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage.

Outcome measures

Measure	Sildenafil n=3 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 52 and End of Treatment (EOT) Baseline	841.73 picograms per milliliter Standard Deviation 1323.533
Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 52 and End of Treatment (EOT) Change at Week 52	-754.90 picograms per milliliter Standard Deviation 1335.370
Change From Baseline in N-terminal Pro Brain Natriuretic Peptide (NT Pro-BNP) at Week 52 and End of Treatment (EOT) Change at EoT	-754.90 picograms per milliliter Standard Deviation 1335.370

SECONDARY outcome

Timeframe: Baseline upto 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	6 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 Participants

SECONDARY outcome

Timeframe: Baseline upto 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	3 Participants
Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

BP measurement is recorded as supine and sitting systolic and diastolic systemic blood pressure: 1) Systolic blood pressure when heart is contracting and it is the maximum arterial pressure during contraction of left ventricle. 2) Diastolic BP when heart is relaxing and it is the minimum arterial pressure during relaxation and dilation of ventricles. Only those categories in which at least 1 participant had data were reported.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Supine Systolic BP	95.4 mmHg Standard Deviation 13.41
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Supine Diastolic BP	55.8 mmHg Standard Deviation 10.87
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Sitting Systolic BP	110.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Sitting Diastolic BP	60.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 4: Supine Systolic BP	5.6 mmHg Standard Deviation 9.91
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 4: Supine Diastolic BP	1.6 mmHg Standard Deviation 13.65
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 4: Sitting Systolic BP	16.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 4: Sitting Diastolic BP	23.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 8: Supine Systolic BP	7.8 mmHg Standard Deviation 14.93
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 8: Supine Diastolic BP	2.3 mmHg Standard Deviation 12.28
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 8: Sitting Systolic BP	-6.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 8: Sitting Diastolic BP	-3.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 16: Supine Systolic BP	7.7 mmHg Standard Deviation 17.62
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 16: Supine Diastolic BP	-1.3 mmHg Standard Deviation 12.22
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 16: Sitting Systolic BP	8.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 16: Sitting Diastolic BP	10.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 28: Supine Systolic BP	7.0 mmHg Standard Deviation 19.31
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 28: Supine Diastolic BP	1.7 mmHg Standard Deviation 9.29
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 40: Supine Systolic BP	-7.5 mmHg Standard Deviation 3.54
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 40: Supine Diastolic BP	2.0 mmHg Standard Deviation 0.00
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 52: Supine Systolic BP	2.0 mmHg Standard Deviation 15.56
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 52: Supine Diastolic BP	10.0 mmHg Standard Deviation 5.66
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 64: Supine Systolic BP	1.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 64: Supine Diastolic BP	8.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 76: Supine Systolic BP	-13.0 mmHg
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 76: Supine Diastolic BP	3.0 mmHg

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

Only those categories in which at least 1 participant had data were reported.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Supine Heart rate	100.2 beats per minute (bpm) Standard Deviation 15.91
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Baseline: Sitting Heart rate	96.0 beats per minute (bpm)
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 4: Supine Heart rate	-1.0 beats per minute (bpm) Standard Deviation 12.08
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 4: Sitting Heart rate	-22.0 beats per minute (bpm)
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 8: Supine Heart rate	-0.5 beats per minute (bpm) Standard Deviation 9.11
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 8: Sitting Heart rate	0.0 beats per minute (bpm)
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 16: Supine Heart rate	3.0 beats per minute (bpm) Standard Deviation 28.69
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 16: Sitting Heart rate	4.0 beats per minute (bpm)
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 28: Supine Heart rate	6.7 beats per minute (bpm) Standard Deviation 14.36
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 40: Supine Heart rate	10.0 beats per minute (bpm) Standard Deviation 16.97
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 52: Supine Heart rate	-2.0 beats per minute (bpm) Standard Deviation 11.31
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 64: Supine Heart rate	17.0 beats per minute (bpm)
Change From Baseline in Heart Rate at Weeks 4, 8, 16, 28, 40, 52, 64, 76, 88, 100, 112 and 124 Change at Week 76: Supine Heart rate	-8.0 beats per minute (bpm)

SECONDARY outcome

Timeframe: Baseline up-to End of treatment (maximum duration of treatment: 119.6 weeks)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Laboratory abnormality criteria: Hematology (hemoglobin, hematocrit, red blood cell count [less than {<}]0.8*lower limit of normal [LLN]; platelets <0.5*LLN, greater than [>]1.75*upper limit of normal [ULN], white blood cells <0.6*LLN, >1.5*ULN; lymphocytes, neutrophils <0.8*LLN, >1.2*ULN, eosinophils, basophils, monocytes >1.2*ULN); liver function (total and direct bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3.0*ULN, total protein, albumin <0.8*LLN, >1.2*ULN); renal (creatinine, blood urea nitrogen >1.3*ULN); electrolytes (sodium <0.95*LLN, >1.05*ULN, potassium, chloride <0.9*LLN, >1.1*ULN; other (glucose <0.6*LLN or >1.5*ULN ); urinalysis (dipstick) urine glucose, urine protein, urine blood/Hemoglobin, [greater than or equal to {>=}1].

Outcome measures

Measure

Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.

Number of Participants With Laboratory Abnormalities

4 Participants

SECONDARY outcome

Timeframe: Screening, Week 16, Week 52 and End of treatment (maximum duration of treatment: 119.6 weeks)

Population: Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure for specified categories.

Criteria for clinically significant abnormality in ECG parameters: Maximum corrected QT interval (QTc) from 450 millisecond (msec) to less than (<) 480 msec, Maximum QTcB interval (Bazett's Correction) from 450 msec to <480 msec, Maximum QTcF interval (Fredericia's Correction) from 450 msec to <480 msec, maximum QTc interval increase from baseline of 30 msec to <60 msec and >=60 msec.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities Screening	4 Participants
Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities Week 16	5 Participants
Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities Week 52	1 Participants
Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities End of Treatment	1 Participants

SECONDARY outcome

Timeframe: Screening up to end of treatment (maximum duration of treatment: 119.6 weeks)

Population: Safety analysis set included all participants who received at least 1 dose of study drug.

Ocular examination measures included external examination of the eye, funduscopy, assessments of visual acuity, and color vision. Ocular examination findings were considered abnormal based on investigator's decision.

Outcome measures

Measure

Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.

Number of Participants With Ocular Examination Abnormalities

0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Pulmonary Artery Systolic and Diastolic Pressure at Week 16 Baseline: Systolic Pressure	82.5 mmHg Standard Deviation 35.51
Change From Baseline in Pulmonary Artery Systolic and Diastolic Pressure at Week 16 Baseline: Diastolic Pressure	42.0 mmHg Standard Deviation 18.19
Change From Baseline in Pulmonary Artery Systolic and Diastolic Pressure at Week 16 Change at Week 16: Systolic Pressure	-9.8 mmHg Standard Deviation 18.01
Change From Baseline in Pulmonary Artery Systolic and Diastolic Pressure at Week 16 Change at Week 16: Diastolic Pressure	-3.5 mmHg Standard Deviation 13.99

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Systemic Artery Systolic and Diastolic Pressure at Week 16 Baseline: Systolic Pressure	95.3 mmHg Standard Deviation 15.20
Change From Baseline in Systemic Artery Systolic and Diastolic Pressure at Week 16 Baseline: Diastolic Pressure	60.2 mmHg Standard Deviation 19.30
Change From Baseline in Systemic Artery Systolic and Diastolic Pressure at Week 16 Change at Week 16: Diastolic Pressure	-1.5 mmHg Standard Deviation 14.25
Change From Baseline in Systemic Artery Systolic and Diastolic Pressure at Week 16 Change at Week 16: Systolic Pressure	0.3 mmHg Standard Deviation 10.21

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

The resistance to blood flow through the pulmonary circulation is known as PVR. It is largely influenced by the caliber of the pulmonary arteries and capillaries and was measured in terms of Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5).

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 Baseline	21.372 Wood units Standard Deviation 11.3408
Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 Change at Week 16	-6.145 Wood units Standard Deviation 10.3499

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

RAP is the blood pressure in the right atrium of the heart. It reflects the amount of blood returning to the heart and the ability of the heart to pump the blood into the arterial system. RAP was measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Right Atrial Pressure (RAP) at Week 16 Baseline	6.5 mmHg Standard Deviation 2.88
Change From Baseline in Right Atrial Pressure (RAP) at Week 16 Change at Week 16	1.3 mmHg Standard Deviation 2.36

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 16 Baseline	8.5 mmHg Standard Deviation 0.84
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 16 Change at Week 16	2.5 mmHg Standard Deviation 1.00

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Cardiac output is simply the amount of blood pumped by the heart per minute.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Cardiac Output (CO) at Week 16 Baseline	2.620 liter per minute Standard Deviation 0.9879
Change From Baseline in Cardiac Output (CO) at Week 16 Change at Week 16	0.420 liter per minute Standard Deviation 0.9076

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Cardiac index is a hemodynamic parameter that relates the cardiac output from left ventricle in one minute to BSA, thus relating heart performance to the size of the individual. CI was calculated as cardiac output in systemic circulation divided by BSA.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Cardiac Index (CI) at Week 16 Baseline	3.070 liter per minute per meter square Standard Deviation 0.7460
Change From Baseline in Cardiac Index (CI) at Week 16 Change at Week 16	0.658 liter per minute per meter square Standard Deviation 1.8912

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

The resistance to blood flow through the systemic circulation is known as SVR. This can be used in measuring blood pressure, blood flow and cardiac function and measured in terms of Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5).

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Systemic Vascular Resistance (SVR) at Week 16 Baseline	26.545 Wood units Standard Deviation 3.0768
Change From Baseline in Systemic Vascular Resistance (SVR) at Week 16 Change at Week 16	-3.403 Wood units Standard Deviation 4.4409

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

SVRI equals systemic vascular resistance (SVR) times BSA. SVR is the resistance to blood flow through the systemic circulation and it was measured in Wood units. Wood unit =80 dyne*seconds per centimetre^5 (dyne*sec/cm^5).

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Systemic Vascular Resistance Index (SVRI) at Week 16 Baseline	23.855 Wood units*meter^2 Standard Deviation 12.1480
Change From Baseline in Systemic Vascular Resistance Index (SVRI) at Week 16 Change at Week 16	-2.378 Wood units*meter^2 Standard Deviation 3.9096

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

SvO2 is the percentage of mixed venous oxygen (amount of oxygen bound to hemoglobin in venous blood). Change from baseline in percentage of mixed venous oxygen was reported in this outcome measure.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Mixed Venous Oxygen Saturation (SvO2) at Week 16 Baseline	65.30 percentage of mixed venous oxygen Standard Deviation 8.549
Change From Baseline in Mixed Venous Oxygen Saturation (SvO2) at Week 16 Change at Week 16	5.38 percentage of mixed venous oxygen Standard Deviation 12.426

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

SaO2 is the percentage of arterial oxygen (amount of oxygen bound to hemoglobin in arterial blood). Change from baseline in percentage of arterial oxygen was reported in this outcome measure.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Arterial Oxygen Saturation (SaO2) at Week 16 Baseline	95.08 percentage of arterial oxygen Standard Deviation 2.730
Change From Baseline in Arterial Oxygen Saturation (SaO2) at Week 16 Change at Week 16	-0.80 percentage of arterial oxygen Standard Deviation 1.691

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16

Population: Pharmacokinetic (PK) parameter analysis set included all participants who have at least 1 of PK parameters of interest.

UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Maximum Observed Plasma Concentration (Cmax) of Sildenafil and UK-103,320 Sildenafil	138.1 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 73
Maximum Observed Plasma Concentration (Cmax) of Sildenafil and UK-103,320 UK-103,320	73.66 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 48

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16

Population: PK parameter analysis set included all participants who have at least 1 of PK parameters of interest.

UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Sildenafil and UK-103,320 Sildenafil	338.9 nanogram*hour per millimeter Geometric Coefficient of Variation 54
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Sildenafil and UK-103,320 UK-103,320	210.2 nanogram*hour per millimeter Geometric Coefficient of Variation 74

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16

Population: PK parameter analysis set included all participants who have at least 1 of PK parameters of interest.

UK-103,320 was the main metabolite of Sildenafil and was produced by cytochrome P450 3A4.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sildenafil and UK-103,320 Sildenafil	1.00 hour Interval 1.0 to 1.97
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sildenafil and UK-103,320 UK-103,320	1.00 hour Interval 1.0 to 1.97

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16

Population: PK parameter analysis set included all participants who have at least 1 of PK parameters of interest. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Terminal half-life is the time measured for the plasma concentration to decrease by one half of its original concentration. UK-103,320 was a main metabolite of sildenafil and was produced by cytochrome P450 3A4.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Terminal Half Life (t1/2) of Sildenafil and UK-103,320 Sildenafil	1.785 hour Interval 1.63 to 1.94
Terminal Half Life (t1/2) of Sildenafil and UK-103,320 UK-103,320	2.110 hour Interval 2.04 to 3.26

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16

Population: PK parameter analysis set included all participants who have at least 1 of PK parameters of interest.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Outcome measures

Measure

Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.

Apparent Oral Clearance (CL/F) of Sildenafil

41.73 liter per hour Geometric Coefficient of Variation 77

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dose (0 hour) on Week 4, 8, 16 and 1, 2, 4, 8 hours post-dose on Week 16

Population: PK parameter analysis set included all participants who have at least 1 of PK parameters of interest. Here, Overall Number of participants analyzed signifies those participants who were evaluable for this measure.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Outcome measures

Measure

Sildenafil n=2 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.

Apparent Volume of Distribution (Vz/F) of Sildenafil

77.90 liter Interval 62.4 to 93.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Acceleration time and ejection time are quantitative Doppler parameters and ratio of acceleration time to ejection time is a useful tool to evaluate the severity of aortic stenosis.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Ratio of Acceleration Time to Ejection Time (AcT/ET) at Week 16 Baseline	0.3038 ratio Standard Deviation 0.09675
Change From Baseline in Ratio of Acceleration Time to Ejection Time (AcT/ET) at Week 16 Change at Week 16	0.0175 ratio Standard Deviation 0.10261

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

The right ventricular Tei Index is an index of myocardial performance. It is defined as the sum of isovolumic contraction time and isovolumic relaxation time divided by the ejection time.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Right Ventricular Tei Index at Week 16 Baseline	0.7540 ratio Standard Deviation 0.48602
Change From Baseline in Right Ventricular Tei Index at Week 16 Change at Week 16	-0.0440 ratio Standard Deviation 0.37618

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Right Ventricular Size at Week 16 Baseline	3.37 centimeter (cm) Standard Deviation 1.216
Change From Baseline in Right Ventricular Size at Week 16 Change at Week 16	-0.40 centimeter (cm) Standard Deviation 0.408

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

The tricuspid valve lies between the right atrium and the right ventricle and is placed in a more apical position than the mitral valve. The annulus separates the right atrium from the right ventricle. Change from baseline in tricuspid valve annulus size (in cm) was reported in this outcome measure.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Tricuspid Valve Annulus Size at Week 16 Baseline	2.190 cm Standard Deviation 0.5636
Change From Baseline in Tricuspid Valve Annulus Size at Week 16 Change at Week 16	-0.103 cm Standard Deviation 0.3727

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Tricuspid regurgitation (insufficiency) is the failure of the tricuspid valve to close properly during systole, leading to the leaking of blood from the right ventricle into the right atrium. Change from baseline in TR-PG peak (in mmHg) was reported in this outcome measure.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Tricuspid Regurgitation - Pressure Gradient (TR-PG) Peak at Week 16 Baseline	73.0 mmHg Standard Deviation 39.31
Change From Baseline in Tricuspid Regurgitation - Pressure Gradient (TR-PG) Peak at Week 16 Change at Week 16	-6.0 mmHg Standard Deviation 33.94

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Pulmonary regurgitation (PR) or insufficiency is a valvular heart disease characterized by an incomplete closure of the pulmonary valve leading to a diastolic reflux into the right ventricle. Change from baseline in PR-PG end-diastole (in mmHg) was reported in this outcome measure.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Pulmonary Regurgitation - Pressure Gradient (PR-PG) End-Diastole at Week 16 Baseline	29.0 mmHg Standard Deviation 14.73
Change From Baseline in Pulmonary Regurgitation - Pressure Gradient (PR-PG) End-Diastole at Week 16 Change at Week 16	3.5 mmHg Standard Deviation 13.44

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug.

Pericardial effusion is the presence of an abnormal amount of fluid in the pericardial cavity, as determined by echocardiography.

Outcome measures

Measure

Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.

Number of Participants With Pericardial Effusion

0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 16

Population: Efficacy analysis set included all participants who received at least 1 dose of study drug. Here, 'Number analyzed' = Participants evaluable for this outcome measure at specified time points.

Tricuspid annular plane systolic excursion is a parameter depicting global right ventricular function. Change from baseline in TAPSE (in cm) was reported in this outcome measure.

Outcome measures

Measure	Sildenafil n=6 Participants Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 16 Baseline	1.47 cm Standard Deviation 0.437
Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE) at Week 16 Change at Week 16	0.18 cm Standard Deviation 0.320

Adverse Events

Sildenafil

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Sildenafil n=6 participants at risk Participants received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Day 1 (Baseline), Weeks 4, 8, and 16 in Part 1 of the study. Participants who completed Part 1 and required continuing treatment with Sildenafil, received 10 mg or 20 mg of Sildenafil (based on their body weight) orally, thrice daily on Weeks 28, 40, 52 and thereafter every 12 weeks until Sildenafil obtained marketing approval (up to a maximum of 119.6 weeks). Participants with \<= 20 kg of body weight received 10 mg dose, thrice daily as powder for oral suspension and participants with \> 20 kg of body weight received 20 mg dose, thrice daily as film-coated tablets.
Cardiac disorders Cardiac failure	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Eye disorders Conjunctivitis allergic	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Gastrointestinal disorders Dental caries	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Gastrointestinal disorders Vomiting	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
General disorders Chest pain	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
General disorders Feeling abnormal	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Infections and infestations Bronchitis	50.0% 3/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Infections and infestations Gastroenteritis	33.3% 2/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Infections and infestations Influenza	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Infections and infestations Nasopharyngitis	50.0% 3/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Infections and infestations Upper respiratory tract infection	50.0% 3/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Investigations Alanine aminotransferase increased	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Investigations Ammonia increased	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Investigations Aspartate aminotransferase increased	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Investigations Weight increased	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Nervous system disorders Headache	33.3% 2/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Reproductive system and breast disorders Dysmenorrhoea	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Reproductive system and breast disorders Erection increased	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Respiratory, thoracic and mediastinal disorders Epistaxis	33.3% 2/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Skin and subcutaneous tissue disorders Acne	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Skin and subcutaneous tissue disorders Dermatitis diaper	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Skin and subcutaneous tissue disorders Dry skin	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Skin and subcutaneous tissue disorders Eczema	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Vascular disorders Flushing	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Eye disorders Vision blurred	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Eye disorders Visual acuity reduced transiently	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Gastrointestinal disorders Colitis	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Infections and infestations Molluscum contagiosum	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Infections and infestations Streptococcal infection	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Investigations Blood urine present	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)
Musculoskeletal and connective tissue disorders Myalgia	16.7% 1/6 • Baseline up to 28 days after last dose of study drug (maximum duration of treatment: 119.6 weeks)

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER