Open Label Study of Sildenafil in Patients With Pulmonary Arterial Hypertension

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00454207
• Collaborator: (none)
• Enrollment: 44
• Locations: 8
• Arm: 1
• Duration (Months): 22.1
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To assess the safety of sildenafil 20 mg TID orally given to Japanese pulmonary arterial hypertension patients (Part 1 and 2) To assess the efficacy after 12 weeks of treatment of sildenafil 20 mg TID orally given to Japanese pulmonary arterial hypertension patients (Part 1)

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension	Drug: sildenafil citrate (UK-92,480)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multi-Center, Open-Label Study to Assess Safety and Efficacy of Sildenafil Citrate 20 mg TID in Subjects With Pulmonary Arterial Hypertension
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: sildenafil citrate (UK-92,480) sildenafil citrate 20 mg TID	Drug: sildenafil citrate (UK-92,480); sildenafil citrate (UK-92,480)

Outcome Measures

Primary Outcome Measures

1. Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：6-minute walk distance at Week 12 minus 6-minute walk distance at baseline. The 6-minute walk distance:total distance walked during the 6-minute walk test.

2. Change in the Mean Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change:Mean pulmonary arterial pressure at Week 12 minus mean pulmonary arterial pressure at baseline.

3. Change in the Pulmonary Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：Pulmonary vascular resistance at Week 12 minus pulmonary vascular resistance at baseline

4. Change in the Cardiac Output From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, week 12]

   Change：Cardiac output at Week 12 minus cardiac output at baseline

Secondary Outcome Measures

1. Change in the 6-minute Walk Distance From Baseline at Week 8 in Participants Who Entered the Study From Part I [Baseline, Week 8]

   Change：6-minute walk distance at Week 8 minus 6-minute walk distance at baseline. The 6-minute walk distance:Total distance walked during the 6- minute walk test.

2. Change in the Systolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：Systolic pulmonary arterial pressure at Week 12 minus Systolic pulmonary arterial pressure at baseline.

3. Change in the Diastolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：Diastolic pulmonary arterial pressure at Week 12 minus diastolic pulmonary arterial pressure at baseline.

4. Change in the Systolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：Systolic systemic blood pressure at Week 12 minus systolic systemic blood pressure at baseline.

5. Change in the Diastolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：Diastolic systemic blood pressure at Week 12 minus diastolic systemic blood pressure at baseline.

6. Change in the Mean Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Mean systemic blood pressure:diastolic blood pressure+(systolic blood pressure-diastolic blood pressure)/3. Change：Mean systemic blood pressure at Week 12 minus mean systemic blood pressure at baseline.

7. Change in the Pulmonary Capillary Wedge Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：Pulmonary capillary wedge pressure at Week 12 minus pulmonary capillary wedge pressure at baseline.

8. Change in the Right Atrial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：Right atrial pressure at Week 12 minus right atrial pressure at baseline.

9. Change in the Cardiac Index From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

   Change：Cardiac index at Week 12 minus cardiac index at baseline.

10. Change in the Heart Rate From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

    Change：Heart rate at Week 12 minus heart rate at baseline.

11. Change in the Pulmonary Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

    Change:Pulmonary vascular resistance index at Week 12 minus pulmonary vascular resistance index at baseline.

12. Change in the Systemic Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

    Change：Systemic vascular resistance at Week 12 minus systemic vascular resistance at baseline.

13. Change in the Systemic Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I [baseline, Week 12]

    Change：Systemic vascular resistance index at Week 12 minus systemic vascular resistance index at baseline.

14. Change in the Mixed Venous Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

    Change：Mixed venous oxygen saturation at Week 12 minus mixed venous oxygen saturation at baseline.

15. Change in the Arterial Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

    Change：Arterial oxygen saturation at Week 12 minus arterial oxygen saturation at baseline.

16. Change in the Arterial Oxygen Partial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I [baseline, Week 12]

    Change：Arterial oxygen partial pressure at Week 12 minus arterial oxygen partial pressure at baseline.

17. Change in the Partial Pressure of Mixed Venous Oxygen From Baseline at Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

    Change：Partial pressure of mixed venous oxygen at Week 12 minus partial pressure of mixed venous oxygen at baseline.

18. Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I [Baseline, Week 12]

    The cross-tabulation table on the WHO functional classes of pulmonary arterial hypertension at baseline and Week 12. The WHO functional classes of pulmonary arterial hypertension:Class I (pulmonary arterial hypertension patients with no limitation in physical activity) to Class IV (pulmonary arterial hypertension patients who can not perform a physical activity without any symptoms).

19. Changes in the BORG Dyspnoea Score From Baseline at Week 8 and Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 8, Week 12]

    Change：BORG dyspnoea score at Week 8 and Week 12 minus BORG dyspnoea score at baseline. BORG dyspnoea score:Scale 0 (no breathlessness at all) to 10 (maximum). The score reflected the maximum degree of dyspnoea that the participants experienced at any time during the 6-minute walk distance.

20. Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 4, Week 8 and Week 12 in Participants Who Entered the Study From Part I [Baseline, Week 4, Week 8, Week 12]

    Change：Plasma brain natriuretic peptide level at Week 4, Week 8 and Week 12 minus plasma brain natriuretic peptide level at baseline

21. Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II [Baseline, Week 12]

    Change：6-minute walk distance at Week 12 minus 6-minute walk distance at baseline. The 6-minute walk distance:Total distance walked during the 6- minute walk test.

22. Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II [Baseline, Week 12]

    The cross-tabulation table on the WHO functional classes of pulmonary arterial hypertension at baseline and Week 12. The WHO functional classes of pulmonary arterial hypertension:Class I (pulmonary arterial hypertension patients with no limitation in physical activity) to Class IV (pulmonary arterial hypertension patients who can not perform a physical activity without any symptoms).

23. Changes in the BORG Dyspnoea Score From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II [Baseline, Week 12]

    Change：BORG dyspnoea score at Week 12 minus BORG dyspnoea score at baseline. BORG dyspnoea score:Scale 0 (no breathlessness at all) to 10 (maximum). The score reflected the maximum degree of dyspnoea that the participants experienced at any time during the 6-minute walk distance.

24. Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 12 in Participants Who Newly Enterd the Study From Part II [Baseline, Week 12]

    Change：Plasma brain natriuretic peptide level at Week 12 minus plasma brain natriuretic peptide level at baseline

25. Maximum Plasma Concentrations (Cmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320 [Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing]

    Maximum plasma concentrations was calculated from the observed value of plasma concentrations in each participant

26. Time to First Occurrence of Maximum Plasma Concentrations (Tmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320 [Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing]

    Time to first occurrence of maximum plasma concentrations were calculated from the observed value of plasma concentrations in each participant.

27. The Area Under the Curve (AUC) From Time 0 to Time 8 Hour of Sildenafil and Sildenafil's Metabolite, UK-103,320 [Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing]

    The area under the curve from time 0 to time 8 hour was calculated from area under the curve in each perticipant on the date of blood sampling using the linear/log trapezoidal rule

28. The Average Plasma Concentration (Css,av) of Sildenafil at Steady State [Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing]

    The average plasma concentration of sildenafil at steady state was calculated from the area under the curve from time 0 to 8 hour/dosing interval (8 hours).

29. The Average Plasma Trough Concentration (Ctrough) of Sildenafil [Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing]

    The average plasma trough concentration of sildenafil was calculated from the observed value before administration of the drug in each participants.

30. Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) [Baseline up to 1.3 years]

    The total number of participants with laboratory test abnormalities without regard to baseline abnormality.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects aged 16 and over, and classified as having pulmonary arterial hypertension

• Subjects who meet the following conditions on right heart catheterization at screening or baseline: mean pulmonary arterial pressure of ≥ 25mmHg and pulmonary capillary wedge pressure of ≤ 15mmHg at rest

• Subjects whose baseline 6-Minute Walk test distance is >100 m and <450 m

Exclusion Criteria:

• Significant Hepatic and/or renal disorder

• Subjects with known hereditary degenerative retinal disorders (such as retinitis pigmentosa) or history of non-arteritic ischemic optic neuropathy (NAION)

• Subjects who are currently receiving nitrates or nitric oxide donors in any form, ritonavir, ketoconazole and itraconazole

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Chiba-shi	Chiba	Japan
2	Pfizer Investigational Site	Kanazawa	Ishikawa	Japan
3	Pfizer Investigational Site	Tsu-shi	Mie	Japan
4	Pfizer Investigational Site	Okayama City	Okayama	Japan
5	Pfizer Investigational Site	Hamamatsu-shi	Shizuoka	Japan
6	Pfizer Investigational Site	Bunkyo-ku	Tokyo	Japan
7	Pfizer Investigational Site	Shinjuku-ku	Tokyo	Japan
8	Pfizer Investigational Site	Tokyo		Japan

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT00454207
• Other Study ID Numbers: A1481252; JapicCTI-070381
• First Posted: Mar 30, 2007
• Last Update Posted: Feb 21, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Pulmonary Arterial Hypertension, PAH
• Additional relevant MeSH terms: Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension; Sildenafil Citrate

Study Results

Participant Flow

Recruitment Details	Eight centers in Japan
Pre-assignment Detail	Twenty-one pulmonary arterial hypertension patients who have never received sildenafil therapy entered the study from Part I period and could continue to study part II period. Twenty-three patients who were continuously using sildenafil entered the study from Part II period.

Arm/Group Title	Sildenafil: Participant Who Entered the Study From Part I	Sildenafil: Participants Who Entered the Study From Part II
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).	Consists of participants who newly entered the study from Part II period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to subjects after approval for the indication of pulmonary arterial hypertension).
Period Title: Overall Study
STARTED	21	23
COMPLETED	17	21
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Sildenafil: Participant Who Entered the Study From Part I	Sildenafil: Participants Who Entered the Study From Part II	Total
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).	Consists of participants who newly entered the study from Part II period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to subjects after approval for the indication of pulmonary arterial hypertension).	Total of all reporting groups
Overall Participants	21	23	44
Age (Count of Participants)
<=18 years	0 0%	1 4.3%	1 2.3%
Between 18 and 65 years	19 90.5%	20 87%	39 88.6%
>=65 years	2 9.5%	2 8.7%	4 9.1%
Sex: Female, Male (Count of Participants)
Female	17 81%	21 91.3%	38 86.4%
Male	4 19%	2 8.7%	6 13.6%
Region of Enrollment (participants) [Number]
Japan	21 100%	23 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：6-minute walk distance at Week 12 minus 6-minute walk distance at baseline. The 6-minute walk distance:total distance walked during the 6-minute walk test.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil: Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [meters]	84.2 (74.9)

2. Primary Outcome

Title	Change in the Mean Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change:Mean pulmonary arterial pressure at Week 12 minus mean pulmonary arterial pressure at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	-4.7 (8.2)

3. Primary Outcome

Title	Change in the Pulmonary Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Pulmonary vascular resistance at Week 12 minus pulmonary vascular resistance at baseline
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [dyne·second/centimeter^5]	-246.49 (301.17)

4. Secondary Outcome

Title	Change in the 6-minute Walk Distance From Baseline at Week 8 in Participants Who Entered the Study From Part I
Description	Change：6-minute walk distance at Week 8 minus 6-minute walk distance at baseline. The 6-minute walk distance:Total distance walked during the 6- minute walk test.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	19
Mean (Standard Deviation) [meters]	87.5 (75.3)

5. Secondary Outcome

Title	Change in the Systolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Systolic pulmonary arterial pressure at Week 12 minus Systolic pulmonary arterial pressure at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	-3.4 (13.4)

6. Secondary Outcome

Title	Change in the Diastolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Diastolic pulmonary arterial pressure at Week 12 minus diastolic pulmonary arterial pressure at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	-3.2 (8.3)

7. Secondary Outcome

Title	Change in the Systolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Systolic systemic blood pressure at Week 12 minus systolic systemic blood pressure at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	0.7 (16.5)

8. Secondary Outcome

Title	Change in the Diastolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Diastolic systemic blood pressure at Week 12 minus diastolic systemic blood pressure at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	-3.1 (9.0)

9. Secondary Outcome

Title	Change in the Mean Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Mean systemic blood pressure:diastolic blood pressure+(systolic blood pressure-diastolic blood pressure)/3. Change：Mean systemic blood pressure at Week 12 minus mean systemic blood pressure at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	-0.9 (12.9)

10. Primary Outcome

Title	Change in the Cardiac Output From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Cardiac output at Week 12 minus cardiac output at baseline
Time Frame	Baseline, week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [liter/minute]	0.556 (1.000)

11. Secondary Outcome

Title	Change in the Pulmonary Capillary Wedge Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Pulmonary capillary wedge pressure at Week 12 minus pulmonary capillary wedge pressure at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	0.68 (3.14)

12. Secondary Outcome

Title	Change in the Right Atrial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Right atrial pressure at Week 12 minus right atrial pressure at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	-0.3 (4.4)

13. Secondary Outcome

Title	Change in the Cardiac Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Cardiac index at Week 12 minus cardiac index at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [liter/minute/meter^2]	0.32 (0.62)

14. Secondary Outcome

Title	Change in the Heart Rate From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Heart rate at Week 12 minus heart rate at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [beats/minute]	-4.14 (7.45)

15. Secondary Outcome

Title	Change in the Pulmonary Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change:Pulmonary vascular resistance index at Week 12 minus pulmonary vascular resistance index at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [dyne*second/centimeter^5/meter^2]	-382.00 (491.80)

16. Secondary Outcome

Title	Change in the Systemic Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Systemic vascular resistance at Week 12 minus systemic vascular resistance at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [dyne*second/centimeter^5]	-265.77 (785.52)

17. Secondary Outcome

Title	Change in the Systemic Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Systemic vascular resistance index at Week 12 minus systemic vascular resistance index at baseline.
Time Frame	baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [dyne*second/centimeter^5/meter^2]	-409.89 (1271.30)

18. Secondary Outcome

Title	Change in the Mixed Venous Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Mixed venous oxygen saturation at Week 12 minus mixed venous oxygen saturation at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [percent saturation]	2.91 (9.05)

19. Secondary Outcome

Title	Change in the Arterial Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Arterial oxygen saturation at Week 12 minus arterial oxygen saturation at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [percent saturation]	0.440 (5.437)

20. Secondary Outcome

Title	Change in the Arterial Oxygen Partial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Arterial oxygen partial pressure at Week 12 minus arterial oxygen partial pressure at baseline.
Time Frame	baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Mean (Standard Deviation) [mmHg]	-2.02 (11.17)

21. Secondary Outcome

Title	Change in the Partial Pressure of Mixed Venous Oxygen From Baseline at Week 12 in Participants Who Entered the Study From Part I
Description	Change：Partial pressure of mixed venous oxygen at Week 12 minus partial pressure of mixed venous oxygen at baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	19
Mean (Standard Deviation) [mmHg]	0.57 (4.35)

22. Secondary Outcome

Title	Changes in the World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension From Baseline at Weeks 12 in Participants Who Entered the Study From Part I
Description	The cross-tabulation table on the WHO functional classes of pulmonary arterial hypertension at baseline and Week 12. The WHO functional classes of pulmonary arterial hypertension:Class I (pulmonary arterial hypertension patients with no limitation in physical activity) to Class IV (pulmonary arterial hypertension patients who can not perform a physical activity without any symptoms).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part I , Functional Class at Baseline: I	Sildenafil:Part I, Functional Class at Baseline: II	Sildenafil, Part I, Functional Class at Baseline: III	Sildenafil, Part I, Functional Class at Baseline:IV
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0, and whose WHO functional class at baseline were I. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).	Consists of participants who entered the study from Part I period in Week 0, and whose WHO functional class at baseline were II. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).	Consists of participants who entered the study from Part I period in Week 0, and whose WHO functional class at baseline were III. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).	Consists of participants who entered the study from Part I period in Week 0, and whose WHO functional class at baseline were IV. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	0	7	13	0
Functional class at Week 12:I	0 0%	1 4.3%
Functional class at Week 12:II	6 28.6%	5 21.7%
Functional class at Week 12:III	1 4.8%	7 30.4%
Functional class at Week 12:IV	0 0%	0 0%

23. Secondary Outcome

Title	Changes in the BORG Dyspnoea Score From Baseline at Week 8 and Week 12 in Participants Who Entered the Study From Part I
Description	Change：BORG dyspnoea score at Week 8 and Week 12 minus BORG dyspnoea score at baseline. BORG dyspnoea score:Scale 0 (no breathlessness at all) to 10 (maximum). The score reflected the maximum degree of dyspnoea that the participants experienced at any time during the 6-minute walk distance.
Time Frame	Baseline, Week 8, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward (Week 12).

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Week 8 (n=19, 0)	-0.84 (1.89)
Week 12 (n=20, 6)	-0.95 (1.94)

24. Secondary Outcome

Title	Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 4, Week 8 and Week 12 in Participants Who Entered the Study From Part I
Description	Change：Plasma brain natriuretic peptide level at Week 4, Week 8 and Week 12 minus plasma brain natriuretic peptide level at baseline
Time Frame	Baseline, Week 4, Week 8, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward (Week 12).

Arm/Group Title	Sildenafil:Part I
Arm/Group Description	Consists of participants who entered the study from Part I period in Week 0. The participants were treated with sildenafil 20 mg three times a day orally in Part I period (12 weeks) and Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	20
Week 4 (n=20, 0)	-78.00 (166.41)
Week 8 (n=19, 0)	-88.25 (178.39)
Week 12 (n=20, 7)	-61.82 (209.96)

25. Secondary Outcome

Title	Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
Description	Change：6-minute walk distance at Week 12 minus 6-minute walk distance at baseline. The 6-minute walk distance:Total distance walked during the 6- minute walk test.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part II
Arm/Group Description	Consists of participants who newly entered the study from Part II period in Week 0 and had been receiving sildenafil at doses higher than 60 mg/day before the start of this study. The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	7
Mean (Standard Deviation) [meters]	-23.5 (34.1)

26. Secondary Outcome

Title	Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
Description	The cross-tabulation table on the WHO functional classes of pulmonary arterial hypertension at baseline and Week 12. The WHO functional classes of pulmonary arterial hypertension:Class I (pulmonary arterial hypertension patients with no limitation in physical activity) to Class IV (pulmonary arterial hypertension patients who can not perform a physical activity without any symptoms).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part II, Functional Class at Baseline: I	Sildenafil:Part II, Functional Class at Baseline: II	Sildenafil: Part II, Functional Class at Baseline: III	Sildenafil: Part II, Functional Class at Baseline: IV
Arm/Group Description	Consists of participants who newly entered the study from Part II period in Week 0, and whose WHO functional class at baseline were I. The participants had been receiving sildenafil at doses higher than 60 mg/day before the start of this study.The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).	Consists of participants who newly entered the study from Part II period in Week 0, and whose who functional class at baseline were II. The participants had been receiving sildenafil at doses higher than 60 mg/day before the start of this study.The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).	Consists of participants who newly entered the study from Part II period in Week 0, and whose WHO functional class at baseline were III. The participants had been receiving sildenafil at doses higher than 60 mg/day before the start of this study.The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).	Consists of participants who newly entered the study from Part II period in Week 0, and whose WHO functional class at baseline were IV. The participants had been receiving sildenafil at doses higher than 60 mg/day before the start of this study.The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	1	6	0	0
Functional class at Week 12: I	1 4.8%	0 0%
Functional class at Week 12: II	0 0%	5 21.7%
Functional class at Week 12: III	0 0%	1 4.3%
Functional class at Week 12: IV	0 0%	0 0%

27. Secondary Outcome

Title	Changes in the BORG Dyspnoea Score From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
Description	Change：BORG dyspnoea score at Week 12 minus BORG dyspnoea score at baseline. BORG dyspnoea score:Scale 0 (no breathlessness at all) to 10 (maximum). The score reflected the maximum degree of dyspnoea that the participants experienced at any time during the 6-minute walk distance.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil: Part II
Arm/Group Description	Consists of participants who newly entered the study from Part II period in Week 0 and had been receiving sildenafil at doses higher than 60 mg/day before the start of this study.The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	6
Mean (Standard Deviation) [scores on a scale]	0.33 (1.21)

28. Secondary Outcome

Title	Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 12 in Participants Who Newly Enterd the Study From Part II
Description	Change：Plasma brain natriuretic peptide level at Week 12 minus plasma brain natriuretic peptide level at baseline
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set, including participants who took at least one dose of study medication and had efficacy measurements at both baseline and post-baseline. Last observation carried forward.

Arm/Group Title	Sildenafil:Part II
Arm/Group Description	Consists of participants who newly entered the study from Part II period in Week 0 and had been receiving sildenafil at doses higher than 60 mg/day before the start of this study.The participants were treated with sildenafil 20 mg three times a day orally in Part II period (long-term treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	7
Mean (Standard Deviation) [picograms/milliliter]	15.91 (55.94)

29. Secondary Outcome

Title	Maximum Plasma Concentrations (Cmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320
Description	Maximum plasma concentrations was calculated from the observed value of plasma concentrations in each participant
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil:Pharmacokinetic Analysis Participant
Arm/Group Description	Consists of participants who received sildenafil monotherapy, without administration of other treatment drugs for pulmonary arterial hypertension, in Part I or II, and satisfied the inclusion criteria for pharmacokinetics evaluation without violating the exclusion criteria. The participants were treated with sildenafil 20 mg three times a day orally in Part I period(12 weeks) and Part II period (longterm treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	9
Sildenafil	164.88 (74.78)
Sildenafil's Metabolite, UK-103,320	87.27 (30.67)

30. Secondary Outcome

Title	Time to First Occurrence of Maximum Plasma Concentrations (Tmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320
Description	Time to first occurrence of maximum plasma concentrations were calculated from the observed value of plasma concentrations in each participant.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil:Pharmacokinetic Analysis Participant
Arm/Group Description	Consists of participants who received sildenafil monotherapy, without administration of other treatment drugs for pulmonary arterial hypertension, in Part I or II, and satisfied the inclusion criteria for pharmacokinetics evaluation without violating the exclusion criteria. The participants were treated with sildenafil 20 mg three times a day orally in Part I period(12 weeks) and Part II period (longterm treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	9
Sildenafil	1.102 (0.499)
Sildenafil's Metabolite, UK-103,320	1.611 (1.024)

31. Secondary Outcome

Title	The Area Under the Curve (AUC) From Time 0 to Time 8 Hour of Sildenafil and Sildenafil's Metabolite, UK-103,320
Description	The area under the curve from time 0 to time 8 hour was calculated from area under the curve in each perticipant on the date of blood sampling using the linear/log trapezoidal rule
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil:Pharmacokinetic Analysis Participant
Arm/Group Description	Consists of participants who received sildenafil monotherapy, without administration of other treatment drugs for pulmonary arterial hypertension, in Part I or II, and satisfied the inclusion criteria for pharmacokinetics evaluation without violating the exclusion criteria. The participants were treated with sildenafil 20 mg three times a day orally in Part I period(12 weeks) and Part II period (longterm treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	9
Sildenafil	545.14 (294.88)
Sildenafil's Metabolite, UK-103,320	365.85 (186.55)

32. Secondary Outcome

Title	The Average Plasma Concentration (Css,av) of Sildenafil at Steady State
Description	The average plasma concentration of sildenafil at steady state was calculated from the area under the curve from time 0 to 8 hour/dosing interval (8 hours).
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil:Pharmacokinetic Analysis Participant
Arm/Group Description	Consists of participants who received sildenafil monotherapy, without administration of other treatment drugs for pulmonary arterial hypertension, in Part I or II, and satisfied the inclusion criteria for pharmacokinetics evaluation without violating the exclusion criteria. The participants were treated with sildenafil 20 mg three times a day orally in Part I period(12 weeks) and Part II period (longterm treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	9
Mean (Standard Deviation) [nanograms/milliliter]	68.14 (36.86)

33. Secondary Outcome

Title	The Average Plasma Trough Concentration (Ctrough) of Sildenafil
Description	The average plasma trough concentration of sildenafil was calculated from the observed value before administration of the drug in each participants.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil:Pharmacokinetic Analysis Participant
Arm/Group Description	Consists of participants who received sildenafil monotherapy, without administration of other treatment drugs for pulmonary arterial hypertension, in Part I or II, and satisfied the inclusion criteria for pharmacokinetics evaluation without violating the exclusion criteria. The participants were treated with sildenafil 20 mg three times a day orally in Part I period(12 weeks) and Part II period (longterm treatment period, until a proper system was established to provide sildenafil to participants after approval for the indication of pulmonary arterial hypertension).
Measure Participants	9
Mean (Standard Deviation) [nanograms/milliliter]	19.608 (12.438)

34. Secondary Outcome

Title	Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Description	The total number of participants with laboratory test abnormalities without regard to baseline abnormality.
Time Frame	Baseline up to 1.3 years

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of the study medication and had any evaluable laboratory test data after treatment.

Arm/Group Title	Sildenafil: Part I and Part II
Arm/Group Description	Consists of participants who entered the study from Part I period plus participants who entered the study from Part II period.
Measure Participants	43
Number [participants]	35 166.7%

Adverse Events

Arm/Group Title	Sildenafil: Part I and Part II
Arm/Group Description	Consists of participants who entered the study from Part I period plus participants who entered the study from Part II period.
All Cause Mortality
	Sildenafil: Part I and Part II
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sildenafil: Part I and Part II
	Affected / at Risk (%)	# Events
Total	7/44 (15.9%)
Cardiac disorders
Cardiac failure	2/44 (4.5%)
Eye disorders
Cataract	1/44 (2.3%)
Gastrointestinal disorders
Nausea	1/44 (2.3%)
Infections and infestations
Nasopharyngitis	1/44 (2.3%)
Pneumonia	1/44 (2.3%)
Investigations
Platelet count decreased	1/44 (2.3%)
Metabolism and nutrition disorders
Anorexia	2/44 (4.5%)
Renal and urinary disorders
Scleroderma renal crisis	1/44 (2.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension	2/44 (4.5%)
Other (Not Including Serious) Adverse Events
	Sildenafil: Part I and Part II
	Affected / at Risk (%)	# Events
Total	42/44 (95.5%)
Gastrointestinal disorders
Diarrhoea	4/44 (9.1%)
General disorders
Oedema peripheral	3/44 (6.8%)
Pyrexia	5/44 (11.4%)
Infections and infestations
Nasopharyngitis	17/44 (38.6%)
Injury, poisoning and procedural complications
Fall	4/44 (9.1%)
Investigations
Platelet count decreased	3/44 (6.8%)
Musculoskeletal and connective tissue disorders
Back pain	3/44 (6.8%)
Nervous system disorders
Dizziness	4/44 (9.1%)
Headache	11/44 (25%)
Psychiatric disorders
Insomnia	3/44 (6.8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/44 (6.8%)
Epistaxis	3/44 (6.8%)
Vascular disorders
Flushing	10/44 (22.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.