A Research Study To Assess The Effectiveness And Safety Of Different Doses Of Oral PF-00489791 In The Treatment Of Adult Patients With Pulmonary Arterial Hypertension

• Drug: PF-00489791
  
  tablet form, 1 mg, single dose (Day 1)
• Drug: PF-00489791
  
  tablet form, 2 mg, single dose (Day 1)
• Drug: PF-00489791
  
  tablet form, 4 mg, single dose (Day 1)
• Drug: PF-00489791
  
  tablet form, 10 mg, single dose (Day 1)
• Drug: PF-00489791
  
  tablet form, 20 mg, single dose (Day 1)
• Drug: placebo
  
  tablet form, single dose (Day 1)
• Drug: sildenafil
  
  tablet form, 20 mg, single dose (Day 1)
  Other Name: Revatio

• Experimental: PF-00489791 1 mg
  
  Intervention: Drug: PF-00489791
• Experimental: PF-00489791 2 mg
  
  Intervention: Drug: PF-00489791
• Experimental: PF-00489791 4 mg
  
  Intervention: Drug: PF-00489791
• Experimental: PF-00489791 10 mg
  
  Intervention: Drug: PF-00489791
• Experimental: PF-00489791 20 mg
  
  Intervention: Drug: PF-00489791
• Placebo Comparator: Placebo
  
  Intervention: Drug: placebo
• Active Comparator: Sildenafil
  
  Observational comparator arm
  Intervention: Drug: sildenafil

Inclusion Criteria:

• Idiopathic or familial pulmonary arterial hypertension (PAH)
• Mean PAP at least 25 mm Hg, PCWP < 15 mm Hg at rest
• For females of child-bearing potential negative pregnancy test at screening and use of contraception during the study and 4 weeks after its completion
• Signed and dated informed consent
• Willingness to comply with the study plan and procedures

Exclusion Criteria:

• pulmonary arterial hypertension (PAH)other than idiopathic or familial
• For females, pregnancy or lactation
• Use of specific PAH treatments, potent CYP3A4 inhibitors, protease inhibitors, alpha blockers or arginine 30 days prior tio randomization and during the study
• Change of dose or class of standard background PAH therapy, i.e. oxygen, calcium channel blockers, digoxin, diuretics 30 days prior tio randomization and during the study
• Large shift in altitude (defined as >5000 feet or 1524 meters) during 90 days prior to baseline visit and/or during the study visit
• Subjects with intracardiac shunts and/or serious heart, lung or other health conditions
• HIV positive subjects
• Subjects participating in another clinical trial with an investigational drug or device
• Subjects with degenerative retinal disorders, history of non-arteritic anterior ischemic optic neuropathy or untreated proliferative diabetic retinopathy
• Allergies and previous intolerance of PDE5 inhibitors
• Alcohol or drug abuse
• Blood donation during the study, or 1 month before or after the study