A Study of Tadalafil in Pediatric Participants With Pulmonary Arterial Hypertension (PAH)

Inclusion Criteria:

• ≥6 months to <18 years of age at screening
• Currently have a diagnosis of PAH that is either:
• idiopathic, including hereditary
• related to connective tissue disease
• related to anorexigen use
• associated with surgical repair of at least 6-month duration of congenitalsystemic to pulmonary shunt (eg, atrial septal defect, ventricular septal defect,patent ductus arteriosus)
• Have a history of a diagnosis of PAH established by a resting mean pulmonary arterypressure (mPAP) ≥25 millimeter of mercury (mm Hg), pulmonary artery wedge pressure ≤15mm Hg, and a pulmonary vascular resistance (PVR) ≥3 Wood units via right heartcatheterization (RHC). In the event that a pulmonary artery wedge pressure cannot beobtained during RHC, participants with a left ventricular end diastolic pressure (LVEDP) <15 mm Hg, with normal left heart function, and absence of mitral stenosis onechocardiography can be eligible for enrollment
• Have a World Health Organization (WHO) functional class value of II or III at the timeof screening
• All participants must be receiving an endothelin receptor antagonist (ERA) (such asbosentan or ambrisentan) and must be on a maintenance dose with no change in dose (other than weight-based adjustments) for at least 12 weeks prior to screening andhave a screening aspartate transaminase (AST)/alanine transaminase (ALT) <3 times theupper limit of normal (ULN)
• If on conventional PAH medication, including but not restricted to, anticoagulants,diuretics, digoxin, and oxygen therapy, the participant must be on stable doses withno changes (other than weight-based adjustments) for at least 4 weeks before screening
• Female participants of childbearing potential must test negative for pregnancy duringscreening. Furthermore, female participants must agree to abstain from sexual activityor to use two different reliable methods of birth control as determined by theInvestigator during the study. Examples of reliable birth control methods include trueabstinence as a lifestyle choice (periodic sexual abstinence method is notacceptable); the use of oral contraceptives; a reliable barrier method of birthcontrol (diaphragms with contraceptive jelly; cervical caps with contraceptive jelly;condoms with contraceptive foam; intrauterine devices)
• Written informed consent from parents (and written assent from appropriately agedparticipants) will be obtained prior to any study procedure being performed

Exclusion Criteria:

• Have pulmonary hypertension related to conditions other than specified above,including but not limited to chronic thromboembolic disease, portal pulmonaryhypertension, 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) 15-18 mm Hg]aortic or mitral valve disease (ie, aortic stenosis, aortic insufficiency, mitralstenosis, 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
• Unrepaired congenital heart disease
• Have a history of angina pectoris or other condition that was treated with long- orshort-acting nitrates within 12 weeks before administration of study drug
• Have severe hepatic impairment, Child-Pugh Grade C
• Have severe renal insufficiency, defined as receiving renal dialysis or having ameasured or estimated creatinine clearance (CC) <30 millimeter per minute (mL/min) (Schwartz Formula)
• Diagnosed with a retinal disorder (eg, hereditary retinal disorders, retinopathy ofthe preterm participant and other retinal disorders)
• Have severe hypotension or uncontrolled hypertension as determined by the Investigator
• Have significant parenchymal lung disease
• Have bronchopulmonary dysplasia
• Concurrent phosphodiesterase type 5 (PDE5) inhibitor therapy (sildenafil orvardenafil) or has received PDE5 inhibitor therapy within 12 weeks prior to the firststudy drug dosing
• Concurrent therapy with prostacyclin or its analogues within 12 weeks of screening
• Commenced or discontinued a chronic conventional PAH medication including but notrestricted to: diuretics, anti-coagulants, digoxin, and oxygen therapy within 4 weeksof screening
• Currently receiving treatment with doxazosin, nitrates, or cancer therapy
• Current treatment with potent Cytochrome P450 3A4 (CYP3A4) inhibitors, such asantiretroviral therapy (protease inhibitor), systemic ketoconazole, or systemicitraconazole, or chronic use of potent CYP3A4 inducers, such as rifampicin
• Are nursing or pregnant
• Have previously completed or withdrawn from this study (LVHV), or any other studyinvestigating tadalafil
• Have received tadalafil therapy within 12 weeks prior to the first study drug dosingor are hypersensitive to tadalafil
• Have allergy to the excipients, notably lactose
• Are currently enrolled in, or discontinued within the last 30 days from, a clinicaltrial involving an investigational product or non-approved use of a drug or device, orconcurrently enrolled in any other type of medical research judged not to bescientifically or medically compatible with this study by the Sponsor
• Unable to take orally administered tablets (without chewing, crushing or breaking) orsuspension
• Are Investigator site personnel directly affiliated with this study or their immediatefamilies. Immediate family is defined as a spouse, parent, child or sibling, whetherbiological or legally adopted
• Diagnosis of Down syndrome