A Pharmacokinetics Study for Pediatric Participants With Pulmonary Arterial Hypertension

During Period I, tadalafil will be administered orally, once daily, at a low dose for approximately 5 weeks followed by a high dose for approximately 5 weeks. Dose levels are calculated based on body weight cohorts. Heavy weight cohort >=40 kg, middle weight cohort >=25 kg to <40 kg. Light weight cohort<25 kg. Participants who complete Period 1 may continue taking tadalafil in Period 2 for at least 2 years. Starting dose will not exceed the maximum weight range dose established in Period 1 and after the first 3 months of Period 2, the dose may be adjusted based on available safety and efficacy information.

Inclusion criteria

• Currently have a diagnosis of PAH that is either:

• idiopathic (including hereditary), related to collagen vascular disease, related to anorexigen use, associated with surgical repair, of at least 6 month duration, of a congenital systemic to pulmonary shunt (for example, atrial septal defect, ventricular septal defect, patent ductus arteriosus).
• Have a history of the diagnosis of PAH established by a resting mean pulmonary artery pressure ≥25 mm Hg, pulmonary artery wedge pressure ≤15 mm Hg, and a pulmonary vascular resistance (PVR) ≥3 Wood units via right heart catheterization. In the event that a pulmonary artery wedge pressure is unable to be obtained during right heart catheterization, participants with a left ventricular end diastolic pressure <15 mm Hg, with normal left heart function, and absence of mitral stenosis on echocardiography can be eligible for enrollment
• Have a World Health Organization (WHO) functional class value of I, II or III at the time of enrollment

Exclusion criteria

• Have pulmonary hypertension related to conditions other than specified above, including but not limited to chronic thromboembolic disease, portal pulmonary hypertension, left-sided heart disease or lung disease and hypoxia
• History of left-sided heart disease, including any of the following:

• clinically significant (pulmonary artery occlusion pressure [PAOP] 15 to 18 mm Hg) aortic or mitral valve disease (that is, aortic stenosis, aortic insufficiency, mitral stenosis, moderate or greater mitral regurgitation)
• pericardial constriction
• restrictive or congestive cardiomyopathy
• left ventricular ejection fraction <40% by multigated radionucleotide angiogram (MUGA), angiography, or echocardiography
• left ventricular shortening fraction <22% by echocardiography
• life-threatening cardiac arrhythmias
• symptomatic coronary artery disease within 5 years of study entry as determined by the physician
• History of atrial septostomy or Potts Shunt within 3 months before administration of study drug
• Unrepaired congenital heart disease