Official Title: “A Multinational, Multicentre, Randomized, Double-Blind Study To Assess The Efficacy And Safety Of Oral Sildenafil 20mg TID Or Placebo When Added To Bosentan In The Treatment Of Subjects, Aged 18 Years And Above, With Pulmonary Arterial Hypertension (PAH).”

To assess the efficacy and safety of sildenafil when added to patients with PAH who are taking bosentan as all or part of their background therapy.

Study Type: Interventional

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

Study Primary Completion Date: October 2009

Intervention(s) in this Clinical Trial

• Drug: Bosentan
  • Bosentan + Placebo for 12 weeks of the study (double blind), then 12 months open label phase (bosentan + sildenafil)
• Drug: Sildenafil Citrate
  • Bosentan + Sildenafil for 12 weeks of the study (double blind), then 12 months open label phase

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Placebo
• Experimental: Active

Primary Measures

• To assess the effect on exercise capacity (as measured by the 6 Minute Walk Test) after 12 weeks
  • Time Frame: Week 12
    Safety Issue?: No

Secondary Measures

• To assess the safety and tolerability of sildenafil (20mg TID) or placebo, when added to subjects with PAH who are currently treated with bosentan, after 12 weeks of treatment.
  • Time Frame: Week 12
    Safety Issue?: No
• To assess the safety and tolerability of the open label treatment of sildenafil (20mg TID) and bosentan therapy in subjects with PAH after 12 months of treatment.
  • Time Frame: 12 months
    Safety Issue?: No
• To assess the effect on other clinical outcome measures (clinical worsening, Borg dyspnoea score and PAH functional class) after 12 weeks of treatment of sildenafil (20mg TID) or placebo when added to bosentan therapy in subjects with PAH.
  • Time Frame: Week 12
    Safety Issue?: No
• To determine the population pharmacokinetic parameters of sildenafil and bosentan and to investigate potential pharmacokinetic interactions between the two compounds in the target patient population.
  • Time Frame: Week 12
    Safety Issue?: No
• To investigate the Pharmacokinetic/Pharmacodynamic (PK/PD) relationship between sildenafil and bosentan exposure on the 6-Minute Walk Test.
  • Time Frame: Week 12
    Safety Issue?: No

Inclusion Criteria:

• Subjects aged 18 and over above with PAH and for which bosentan therapy is indicated according to national license
• Subjects with a mean pulmonary artery pressure of >25mmHg and a pulmonary artery wedge pressure of <15mmHg at rest via right heart catheterization within 3 years prior to randomization.
• Subjects whose baseline 6 Minute Walk Test distance is >100m and < 450m.

Exclusion Criteria:

• PAH secondary to any aetiology including congenital heart disease other than those specified in the

  inclusion criteria

• Subjects whose 6 Minute Walk Test may be limited by conditions other than PAH related dyspnoea or fatigue eg. claudication from vascular insufficiency or arthritis.

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  

Overall Contact: Pfizer CT.gov Call Center 1-800-718-1021 

Information obtained from ClinicalTrials.gov on October 07, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00323297

Study ID Number: A1481243

ClinicalTrials.gov Identifier: NCT00323297

Health Authority: United States: Food and Drug Administration

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