Official Title: “A Multinational, Multicentre, Randomized, Parallel Group, Double-Blind Study To Assess The Efficacy and Safety Of 1 mg, 5 mg and 20 mg TID of Oral Sildenafil in the Treatment of Subjects Aged 18 Years and Over With Pulmonary Arterial Hypertension (PAH)”

To demonstrate a dose response for 1 mg, 5 mg and 20 mg TID oral sildenafil for the treatment of subjects with PAH.

Study Type: Interventional

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

Intervention(s) in this Clinical Trial

• Drug: Sildenafil citrate
  • oral, 20 mg, tid
• Drug: Sildenafil citrate
  • oral 1 mg, tid
• Drug: Sildenafil citrate
  • oral 5 mg, tid
• Drug: Sildenafil citrate
  • oral 20 mg, tid

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Sildenafil High dose
• Experimental: Sildenafil Low dose
• Experimental: Sildenafil medium dose
• Experimental: Sildenafil - Open label Phase
  • Open label extension from week 12 to week 24.

Primary Measures

• The change from baseline in the total distance walked during the 6MWT at Week 12 of the study.
  • Time Frame: Week 12
    Safety Issue?: No

Secondary Measures

• Change from baseline at Week 12 in the pulmonary hypertension criteria for functional capacity and therapeutic class.
  • Time Frame: Week 12
    Safety Issue?: No
• Change from baseline at Week 12 in BNP and pro-BNP levels.
  • Time Frame: Week 12
    Safety Issue?: No
• Change from baseline at Week 12 in the BORG dyspnoea score.
  • Time Frame: Week 12
    Safety Issue?: No
• Change from baseline at Week 12 in mean pulmonary artery pressure (mPAP).
  • Time Frame: Week 12
    Safety Issue?: No
• Time from randomization to the first occurrence of clinical worsening defined as death or lung transplantation or hospitalisation due to pulmonary hypertension or initiation of prostacyclin therapy or initiation of bosentan therapy.
  • Time Frame: Week 12
    Safety Issue?: Yes

Inclusion Criteria:

• Subjects with PAH (i.e. IPAH or secondary to connective tissue disease or with surgical repair of ASD, VSD, PDA, aorto-pulmonary window) whose baseline six minute walk test distance is >/= 100 m and </= 450 m.
• Subjects with a mean pulmonary artery pressure of >/= 25 mmHg and a pulmonary artery wedge pressure of </= 15 mmHg at rest via right heart catheterization performed within 12 weeks prior to randomization.

Exclusion Criteria:

• Subjects whose 6 Minute Walk Distance may be limited by conditions other than PAH related dyspnoea or fatigue, e.g. claudication from vascular insufficiency or significant arthritis.
• Subjects who are currently receiving any forms of chronic treatment for PAH such as prostacyclin, PDE-5 inhibitors, endothelin-receptor antagonists, nitrates or nitric oxide donors (e.g. arginine supplement, nicorandil) in any form, protease inhibitors such as ritonavir and saquinavir, ketoconazole, itraconazole, and alpha blockers.
• Subjects previously receiving any of these drugs must have stopped use for a period of at least 1 month prior to screening, except in the case of bosentan or prostacyclin (3 months).

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 August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00430716

Study ID Number: A1481244

ClinicalTrials.gov Identifier: NCT00430716

Health Authority: United States: Food and Drug Administration

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