Open Label Study of Sildenafil in Patients With Pulmonary Arterial Hypertension

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”

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)

Intervention(s) in this Clinical Trial

• Drug: sildenafil citrate (UK-92,480)
  • sildenafil citrate (UK-92,480)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: sildenafil citrate (UK-92,480)
  • sildenafil citrate 20 mg TID

Primary Measures

• Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Mean Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Pulmonary Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Cardiac Output From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, week 12
    Safety Issue?: No

Secondary Measures

• Change in the 6-minute Walk Distance From Baseline at Week 8 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 8
    Safety Issue?: No
• Change in the Systolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Diastolic Pulmonary Arterial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Systolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Diastolic Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Mean Systemic Blood Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Pulmonary Capillary Wedge Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Right Atrial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Cardiac Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Heart Rate From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Pulmonary Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Systemic Vascular Resistance From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Systemic Vascular Resistance Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: baseline, Week 12
    Safety Issue?: No
• Change in the Mixed Venous Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Arterial Oxygen Saturation From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the Arterial Oxygen Partial Pressure From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: baseline, Week 12
    Safety Issue?: No
• Change in the Partial Pressure of Mixed Venous Oxygen From Baseline at Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• 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
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Changes in the BORG Dyspnoea Score From Baseline at Week 8 and Week 12 in Participants Who Entered the Study From Part I
  • Time Frame: Baseline, Week 8, Week 12
    Safety Issue?: No
• 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
  • Time Frame: Baseline, Week 4, Week 8, Week 12
    Safety Issue?: No
• Change in the 6-minute Walk Distance From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Change in the World Health Organization (WHO) Functional Class From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Changes in the BORG Dyspnoea Score From Baseline at Week 12 in Participants Who Newly Entered the Study From Part II
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Changes in the the Plasma Brain Natriuretic Peptide Level From Baseline at Week 12 in Participants Who Newly Enterd the Study From Part II
  • Time Frame: Baseline, Week 12
    Safety Issue?: No
• Maximum Plasma Concentrations (Cmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320
  • Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
    Safety Issue?: No
• Time to First Occurrence of Maximum Plasma Concentrations (Tmax) of Sildenafil and Sildenafil's Metabolite, UK-103,320
  • Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
    Safety Issue?: No
• The Area Under the Curve (AUC) From Time 0 to Time 8 Hour of Sildenafil and Sildenafil's Metabolite, UK-103,320
  • Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
    Safety Issue?: No
• The Average Plasma Concentration (Css,av) of Sildenafil at Steady State
  • Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
    Safety Issue?: No
• The Average Plasma Trough Concentration (Ctrough) of Sildenafil
  • Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
    Safety Issue?: No
• Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
  • Time Frame: Baseline up to 1.3 years
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Pfizer Industry

Overall Clinical Trial Officials and Contacts

Pfizer CT.gov Call Center Study Director Pfizer  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00454207

Study ID Number: A1481252

ClinicalTrials.gov Identifier: NCT00454207

Health Authority: Japan: Ministry of Health, Labor and Welfare

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