A Study to Assess the Efficacy and Safety of 20, 40, and 80mg of Sildenafil Three Times a Day in the Treatment of Pulmonary Arterial Hypertension

January 28, 2021 updated by: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

A Multinational, Multi-centre, Randomised, Double-blind, Double-dummy, Placebo-controlled Study to Assess the Efficacy and Safety of 20, 40, and 80mg TID Sildenafil in the Treatment of Pulmonary Arterial Hypertension in Subjects Aged 18 Years and Over

To evaluate the effect of three doses of oral sildenafil (20, 40 and 80 mg three times a day [TID]) on exercise capacity, as measured by the 6-Minute Walk test, as well as the safety and tolerability, after 12 weeks of treatment in subjects with pulmonary arterial hypertension who are aged 18 years and over. To investigate the plasma concentration-effect relationship and to determine the population pharmacokinetic (PK) parameters.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

275

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

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • Pfizer Investigational Site
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Pfizer Investigational Site
  • Belgium
      • Bruxelles, Belgium, 1070
        • Pfizer Investigational Site
      • Leuven, Belgium, 3000
        • Pfizer Investigational Site
  • Brazil
    • SP
      • Sao Paulo, SP, Brazil, 05403-900
        • Pfizer Investigational Site
  • Czechia
      • Prague 4, Czechia, 140 00
        • Pfizer Investigational Site
      • Prague 4, Czechia, 140 21
        • Pfizer Investigational Site
  • Denmark
      • Kobenhavn, Denmark, 2100
        • Pfizer Investigational Site
  • France
      • Clamart, France, 92141
        • Pfizer Investigational Site
  • Germany
      • Berlin, Germany, 13353
        • Pfizer Investigational Site
      • Giessen, Germany, 35385
        • Pfizer Investigational Site
      • Giessen, Germany, 35392
        • Pfizer Investigational Site
      • Hannover, Germany, 30625
        • Pfizer Investigational Site
      • Leipzig, Germany, 04103
        • Pfizer Investigational Site
  • Hong Kong
      • Shatin N T, Hong Kong
        • Pfizer Investigational Site
  • Hungary
    • Pest
      • Budapest, Pest, Hungary, 1529
        • Pfizer Investigational Site
    • Zala
      • Zalaegerszeg, Zala, Hungary, 8900
        • Pfizer Investigational Site
  • Israel
      • Petach Tikva, Israel, 49100
        • Pfizer Investigational Site
      • Tel Hashomer, Israel, 52621
        • Pfizer Investigational Site
  • Italy
      • Bologna, Italy, 40138
        • Pfizer Investigational Site
      • Pisa, Italy, 56124
        • Pfizer Investigational Site
      • Pisa, Italy, 56126
        • Pfizer Investigational Site
  • Korea, Republic of
      • Suwon, Korea, Republic of, 442-721
        • Pfizer Investigational Site
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • Pfizer Investigational Site
  • Mexico
      • Tlalpan, Mexico
        • Pfizer Investigational Site
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Pfizer Investigational Site
  • Norway
      • Oslo, Norway, NO-0027
        • Pfizer Investigational Site
  • Poland
      • Katowice, Poland, 40-057
        • Pfizer Investigational Site
      • Warszawa, Poland, 01-138
        • Pfizer Investigational Site
      • Warszawa, Poland, 03-709
        • Pfizer Investigational Site
      • Zabrze, Poland, 41-800
        • Pfizer Investigational Site
  • Singapore
      • Singapore, Singapore, 168752
        • Pfizer Investigational Site
  • South Africa
      • Cape Town, South Africa, 7700
        • Pfizer Investigational Site
      • Johannesburg, South Africa, 2193
        • Pfizer Investigational Site
      • Parow, South Africa
        • Pfizer Investigational Site
  • Spain
      • Barcelona, Spain, 08035
        • Pfizer Investigational Site
      • Barcelona, Spain, 08036
        • Pfizer Investigational Site
      • Madrid, Spain, 28041
        • Pfizer Investigational Site
  • Sweden
      • Goteborg, Sweden, 413 45
        • Pfizer Investigational Site
      • Molndal, Sweden, 431 80
        • Pfizer Investigational Site
  • United Kingdom
      • Glasgow, United Kingdom, G11 6NT
        • Pfizer Investigational Site
      • HIGH Heaton, Newcastle-upon-tyne, United Kingdom, NE7 7DW
        • Pfizer Investigational Site
    • Cambridgeshire
      • Papworth Everard, Cambridgeshire, United Kingdom, CB3 8RE
        • Pfizer Investigational Site
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Pfizer Investigational Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Pfizer Investigational Site
      • Birmingham, Alabama, United States, 35294
        • Pfizer Investigational Site
      • Birmingham, Alabama, United States, 35294-0006
        • Pfizer Investigational Site
    • California
      • La Jolla, California, United States, 92037
        • Pfizer Investigational Site
      • La Jolla, California, United States, 92093
        • Pfizer Investigational Site
      • Los Angeles, California, United States, 90095
        • Pfizer Investigational Site
      • Los Angeles, California, United States, 90033
        • Pfizer Investigational Site
      • Los Angeles, California, United States, 90024
        • Pfizer Investigational Site
      • San Diego, California, United States, 92037
        • Pfizer Investigational Site
      • Torrance, California, United States, 90502
        • Pfizer Investigational Site
      • Torrance, California, United States, 90509
        • Pfizer Investigational Site
    • Colorado
      • Aurora, Colorado, United States, 80010
        • Pfizer Investigational Site
      • Denver, Colorado, United States, 80262
        • Pfizer Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Pfizer Investigational Site
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • Pfizer Investigational Site
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Pfizer Investigational Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Pfizer Investigational Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Pfizer Investigational Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Pfizer Investigational Site
    • New York
      • New York, New York, United States, 10032
        • Pfizer Investigational Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Pfizer Investigational Site
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Pfizer Investigational Site
    • Texas
      • Houston, Texas, United States, 77030
        • Pfizer Investigational Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • 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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Included patients had primary pulmonary arterial hypertension, pulmonary hypertension secondary to connective tissue disease, or pulmonary hypertension with surgical repair at least 5 years previously; a mean pulmonary artery pressure greater than or equal to 25 mmHg and a pulmonary artery wedge pressure of less than or equal to 15 mmHg at rest, via right heart catheterisation within 21 days prior to randomisation; and a baseline 6-Minute Walk test distance of 100 m to 450 m.

Exclusion Criteria:

Subjects with congenital heart disease, pulmonary hypertension due to thromboembolism, HIV, chronic obstructive airway disease, congestive heart failure or schistosomiasis; subjects with significant (ie > 2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation; and acutely decompensated heart failure within the previous 30 days; subjects with pulmonary hypertension secondary to any other etiology other than those specified in the inclusion criteria.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 2
Drug: sildenafil
sildenafil 40 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Drug: sildenafil
sildenafil 80 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks; initially, patients received 40mg TID for one week and were then up-titrated to 80mg TID
Drug: sildenafil
sildenafil 20 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Active Comparator: Arm 1
Drug: sildenafil
sildenafil 40 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Drug: sildenafil
sildenafil 80 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks; initially, patients received 40mg TID for one week and were then up-titrated to 80mg TID
Drug: sildenafil
sildenafil 20 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Placebo Comparator: Arm 4
Drug: placebo
placebo by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Active Comparator: Arm 3
Drug: sildenafil
sildenafil 40 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
Drug: sildenafil
sildenafil 80 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks; initially, patients received 40mg TID for one week and were then up-titrated to 80mg TID
Drug: sildenafil
sildenafil 20 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in exercise capacity, as measured by distance walked in six minutes (6-Minute Walk test).
Time Frame: Week 12
Week 12

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in mean pulmonary arterial pressure
Time Frame: Week 12
Week 12
Time from randomisation to the first occurrence of clinical worsening (death or lung transplantation or hospitalisation due to pulmonary hypertension or initiation of prostacyclin therapy or initiation of bosentan therapy)
Time Frame: Week 0 to 12
Week 0 to 12
Change from baseline in the BORG dyspnoea score
Time Frame: Week 12
Week 12
Change from baseline in pulmonary hypertension criteria for functional capacity and therapeutic class
Time Frame: Week 12
Week 12
Change from baseline in the 8 dimensions of SF-36 (Physical functioning, Role functioning, Bodily pain, General health, Vitality, Social functioning, Mental health and Reported health transition)
Time Frame: Week 4 and Week 12
Week 4 and Week 12
Change from baseline at Weeks 4 and 12 in the 5 dimensions of ED5Q (Mobility, Self care, Usual Activities, Pain/Discomfort and Anxiety/Depression)
Time Frame: Week 4 and Week 12
Week 4 and Week 12
Patient overall preference assessment
Time Frame: Week 12
Week 12
Change in Chronic Use of Background Therapy for Pulmonary Arterial Hypertension
Time Frame: throughout the study
throughout the study
Change from baseline in hemodynamic parameters
Time Frame: Week 12
Week 12

Collaborators and Investigators

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

Sponsor

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

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.

General Publications

Helpful Links

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

October 1, 2002

Study Completion (Actual)

November 1, 2003

Study Registration Dates

First Submitted

March 20, 2008

First Submitted That Met QC Criteria

March 20, 2008

First Posted (Estimate)

March 27, 2008

Study Record Updates

Last Update Posted (Actual)

February 1, 2021

Last Update Submitted That Met QC Criteria

January 28, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A1481140

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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