Open Label Study of Sildenafil in Patients With Pulmonary Arterial Hypertension

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)

Study Overview

Status

Completed

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Tokyo, Japan
        • Pfizer Investigational Site
    • Chiba
      • Chiba-shi, Chiba, Japan
        • Pfizer Investigational Site
    • Ishikawa
      • Kanazawa, Ishikawa, Japan
        • Pfizer Investigational Site
    • Mie
      • Tsu-shi, Mie, Japan
        • Pfizer Investigational Site
    • Okayama
      • Okayama City, Okayama, Japan
        • Pfizer Investigational Site
    • Shizuoka
      • Hamamatsu-shi, Shizuoka, Japan
        • Pfizer Investigational Site
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan
        • Pfizer Investigational Site
      • Shinjuku-ku, Tokyo, Japan
        • Pfizer Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
Baseline, Week 12
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
Change:Mean pulmonary arterial pressure at Week 12 minus mean pulmonary arterial pressure at baseline.
Baseline, Week 12
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
Change:Pulmonary vascular resistance at Week 12 minus pulmonary vascular resistance at baseline
Baseline, Week 12
Change in the Cardiac Output From Baseline at Week 12 in Participants Who Entered the Study From Part I
Time Frame: Baseline, week 12
Change:Cardiac output at Week 12 minus cardiac output at baseline
Baseline, week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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

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.

Baseline, Week 8
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
Change:Systolic pulmonary arterial pressure at Week 12 minus Systolic pulmonary arterial pressure at baseline.
Baseline, Week 12
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
Change:Diastolic pulmonary arterial pressure at Week 12 minus diastolic pulmonary arterial pressure at baseline.
Baseline, Week 12
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
Change:Systolic systemic blood pressure at Week 12 minus systolic systemic blood pressure at baseline.
Baseline, Week 12
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
Change:Diastolic systemic blood pressure at Week 12 minus diastolic systemic blood pressure at baseline.
Baseline, Week 12
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

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.

Baseline, Week 12
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
Change:Pulmonary capillary wedge pressure at Week 12 minus pulmonary capillary wedge pressure at baseline.
Baseline, Week 12
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
Change:Right atrial pressure at Week 12 minus right atrial pressure at baseline.
Baseline, Week 12
Change in the Cardiac Index From Baseline at Week 12 in Participants Who Entered the Study From Part I
Time Frame: Baseline, Week 12
Change:Cardiac index at Week 12 minus cardiac index at baseline.
Baseline, Week 12
Change in the Heart Rate From Baseline at Week 12 in Participants Who Entered the Study From Part I
Time Frame: Baseline, Week 12
Change:Heart rate at Week 12 minus heart rate at baseline.
Baseline, Week 12
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
Change:Pulmonary vascular resistance index at Week 12 minus pulmonary vascular resistance index at baseline.
Baseline, Week 12
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
Change:Systemic vascular resistance at Week 12 minus systemic vascular resistance at baseline.
Baseline, Week 12
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
Change:Systemic vascular resistance index at Week 12 minus systemic vascular resistance index at baseline.
baseline, Week 12
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
Change:Mixed venous oxygen saturation at Week 12 minus mixed venous oxygen saturation at baseline.
Baseline, Week 12
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
Change:Arterial oxygen saturation at Week 12 minus arterial oxygen saturation at baseline.
Baseline, Week 12
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
Change:Arterial oxygen partial pressure at Week 12 minus arterial oxygen partial pressure at baseline.
baseline, Week 12
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
Change:Partial pressure of mixed venous oxygen at Week 12 minus partial pressure of mixed venous oxygen at baseline.
Baseline, Week 12
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
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).
Baseline, Week 12
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
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.
Baseline, Week 8, Week 12
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
Change:Plasma brain natriuretic peptide level at Week 4, Week 8 and Week 12 minus plasma brain natriuretic peptide level at baseline
Baseline, Week 4, Week 8, Week 12
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
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.
Baseline, Week 12
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
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).
Baseline, Week 12
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
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.
Baseline, Week 12
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
Change:Plasma brain natriuretic peptide level at Week 12 minus plasma brain natriuretic peptide level at baseline
Baseline, Week 12
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
Maximum plasma concentrations was calculated from the observed value of plasma concentrations in each participant
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
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
Time to first occurrence of maximum plasma concentrations were calculated from the observed value of plasma concentrations in each participant.
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
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
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
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
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
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).
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
The Average Plasma Trough Concentration (Ctrough) of Sildenafil
Time Frame: 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.
Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours after dosing
Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Time Frame: Baseline up to 1.3 years
The total number of participants with laboratory test abnormalities without regard to baseline abnormality.
Baseline up to 1.3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

March 28, 2007

First Submitted That Met QC Criteria

March 28, 2007

First Posted (Estimate)

March 30, 2007

Study Record Updates

Last Update Posted (Actual)

February 21, 2021

Last Update Submitted That Met QC Criteria

January 28, 2021

Last Verified

January 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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