Official Title: “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 Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study

Intervention(s) in this Clinical Trial

• 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: placebo
  • placebo by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks
• Drug: sildenafil
  • sildenafil 20 mg by mouth three times daily (TID), with doses at least 6 hours apart, for 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Arm 1
• Active Comparator: Arm 2
• Active Comparator: Arm 3
• Placebo Comparator: Arm 4

Primary Measures

• Change from baseline in exercise capacity, as measured by distance walked in six minutes (6-Minute Walk test).
  • Time Frame: Week 12
    Safety Issue?: No

Secondary Measures

• Change from baseline in mean pulmonary arterial pressure
  • Time Frame: Week 12
    Safety Issue?: No
• 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
    Safety Issue?: No
• Change from baseline in the BORG dyspnoea score
  • Time Frame: Week 12
    Safety Issue?: No
• Change from baseline in pulmonary hypertension criteria for functional capacity and therapeutic class
  • Time Frame: Week 12
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• Patient overall preference assessment
  • Time Frame: Week 12
    Safety Issue?: No
• Change in Chronic Use of Background Therapy for Pulmonary Arterial Hypertension
  • Time Frame: throughout the study
    Safety Issue?: No
• Change from baseline in hemodynamic parameters
  • Time Frame: Week 12
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Pfizer

Overall Clinical Trial Officials and Contacts

Pfizer CT.gov Call Center Study Director Pfizer  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00644605

Study ID Number: A1481140

ClinicalTrials.gov Identifier: NCT00644605

Health Authority: United States: Food and Drug Administration

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