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

Completed · Phase 3 · Has a placebo group

Conditions studied: Hypertension, Pulmonary

In brief

The main purpose of this study is to evaluate the safety and efficacy of tadalafil in pediatric participants with pulmonary arterial hypertension. Participants will receive study treatment for 6 months in the double-blind period (Period 1), and then will be eligible to enroll into an open-label 2 year extension period (Period 2) during which participants will receive tadalafil.

Key facts

Study ID

NCT01824290

Run by

Eli Lilly and Company

People needed

35

Starts

2014-02-05

Expected to finish

2021-03-10

Last updated by the study team

2021-11-05

Who can join

Age: 1 and older, up to 17. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• ≥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 congenital systemic 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 artery pressure (mPAP) ≥25 millimeter of mercury (mm Hg), pulmonary artery wedge pressure ≤15 mm Hg, and a pulmonary vascular resistance (PVR) ≥3 Wood units via right heart catheterization (RHC). In the event that a pulmonary artery wedge pressure cannot be obtained during RHC, participants with a left ventricular end diastolic pressure (LVEDP) <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 II or III at the time of screening
• All participants must be receiving an endothelin receptor antagonist (ERA) (such as bosentan 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 and have a screening aspartate transaminase (AST)/alanine transaminase (ALT) <3 times the upper 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 with no changes (other than weight-based adjustments) for at least 4 weeks before screening
• Female participants of childbearing potential must test negative for pregnancy during screening. Furthermore, female participants must agree to abstain from sexual activity or to use two different reliable methods of birth control as determined by the Investigator during the study. Examples of reliable birth control methods include true abstinence as a lifestyle choice (periodic sexual abstinence method is not acceptable); the use of oral contraceptives; a reliable barrier method of birth control (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 aged participants) will be obtained prior to any study procedure being performed

You may not qualify if…

• 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) 15-18 mm Hg] aortic or mitral valve disease (ie, 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
• Unrepaired congenital heart disease
• Have a history of angina pectoris or other condition that was treated with long- or short-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 a measured or estimated creatinine clearance (CC) <30 millimeter per minute (mL/min) (Schwartz Formula)
• Diagnosed with a retinal disorder (eg, hereditary retinal disorders, retinopathy of the 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 or vardenafil) or has received PDE5 inhibitor therapy within 12 weeks prior to the first study drug dosing
• Concurrent therapy with prostacyclin or its analogues within 12 weeks of screening
• Commenced or discontinued a chronic conventional PAH medication including but not restricted to: diuretics, anti-coagulants, digoxin, and oxygen therapy within 4 weeks of screening
• Currently receiving treatment with doxazosin, nitrates, or cancer therapy
• Current treatment with potent Cytochrome P450 3A4 (CYP3A4) inhibitors, such as antiretroviral therapy (protease inhibitor), systemic ketoconazole, or systemic itraconazole, 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 study investigating tadalafil
• Have received tadalafil therapy within 12 weeks prior to the first study drug dosing or are hypersensitive to tadalafil

Where it is running

• Children's Heathcare of Atlanta, Inc. at Egleston — Atlanta, Georgia, United States
• Childrens Hospital of Michigan — Detroit, Michigan, United States
• Cincinnati Childrens Hospital Medical Center — Cincinnati, Ohio, United States
• Nationwide Children's Hosp — Columbus, Ohio, United States
• Vanderbilt Univeristy School of Medicine — Nashville, Tennessee, United States
• Texas Childrens Hospital — Houston, Texas, United States
• Primary Childrens Medical Center — Salt Lake City, Utah, United States
• AKH — Vienna, Austria
• Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg — Leuven, Belgium
• Pronto Socorro Cardiologico de Pernambuco-PROCAPE — Recife, Pernambuco, Brazil
• Irmandade da Santa Casa de Misericordia de Porto Alegre — Porto Alegre, Rio Grande do Sul, Brazil
• Instituto Dante Pazzanese de Cardiologia — São Paulo, São Paulo, Brazil
• UNIFESP - Escola Paulista de Medicina — São Paulo, São Paulo, Brazil
• CHU Hopital d'enfants de la Timone — Marseille, France
• GH Necker - Enfants Malades — Paris, France
• Hopital Haut Leveque - Group hospitalier Sud — Pessac, France
• Chu de Toulouse - Hopital des Enfants — Toulouse, France
• Universitätsklinikum Heidelberg — Heidelberg, Baden-Wurttemberg, Germany
• Universitätsklinikum Ulm — Ulm, Baden-Wurttemberg, Germany
• Sheba Medical Center — Tel Litwinsky, Ramat Gan, Israel
• Schneider Medical Center — Petah Tikva, Israel
• Istituto Giannina Gaslini Ospedale Pediatrico I.R.C.C.S. — Genova, GE, Italy
• Ospedale V. Monaldi — Naples, Italy
• Ospedale Bambino Gesu — Roma, Italy
• Gunma Children's Medical Center — Shibukawa, Gunma, Japan

Full record on ClinicalTrials.gov

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