A study in children with Pulmonary Arterial Hypertension to assess the safety of Tadalafil as the dose increases, as well as how the drug works in the body

Phase 1

• Conditions: Pulmonary Arterial Hypertension; MedDRA version: 18.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2011-001873-24-PL
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-09
• Last Update Posted: 29 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Pediatric patients (=6 months to <18 years of age) at time of screening with confirmed PAH.
Patients are eligible to be included in the study only if they meet all of the following criteria:
[1] =6 months to <18 years of age (at screening).
[2] 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).
[3] 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, patients 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.
[4] Have a WHO functional class value of I, II or III at the time of enrollment.
[5] Patients with PAH either naïve to PAH specific therapy or receiving endothelin receptor antagonists (ERA). If on an ERA (that is, bosentan or ambrisentan), must be on a maintenance dose, with no change in dose (other than weight-based adjustments) for =12 weeks prior to screening and have a screening aspartate transaminase (AST) or alanine transaminase (ALT) <3 times the upper limit of normal.
[6] If on conventional PAH medication, including but not restricted to, calcium channel blockers, diuretics, digoxin, and oxygen therapy, the patient must be on stable doses with no changes (other than weight-based adjustments) for at least 4 weeks before screening.
[7] Have a chest radiograph (CXR) within 6 months of screening that shows clear lung fields or no more than mild patchy (not diffuse) interstitial infiltrates.
[8] Female patients of childbearing potential must test negative for pregnancy during screening. Furthermore, female patients must agree to abstain from sexual activity or to use a reliable method 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).
[9] Written informed consent from parents or guardians (and written assent from appropriately aged patients) will be obtained prior to any study procedure being performed.
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients are not eligible to be included in the study if they meet any of the following exclusion criteria:
[10] Have pulmonary hypertension related to conditions other than specified above, including but not limited to chronic thromboembolic disease, portal pulmonary hypertension, leftsided heart disease or lung disease and hypoxia.
[11] 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.
[12] History of Potts Shunt within 3 months before administration of study drug.
[13] Unrepaired congenital heart disease.
[14] Concurrent PDE-5 inhibitor therapy (sildenafil or vardenafil) or has received PDE-5 inhibitor therapy within 24 hours prior to the first study drug dosing (baseline visit).
[15] Concurrent therapy with prostacyclin or its analogues.
[16] Commence or discontinue a conventional PAH medication including but not restricted to: calcium channel blockers, diuretics, anti-coagulants, digoxin, and oxygen therapy within 4 weeks prior to screening.
[17] 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.
[18] Currently receiving treatment with doxazosin, nitrates or cancer therapy.
[19] Current treatment with potent CYP3A4 inhibitors, such as
antiretroviral therapy (protease inhibitor), systemic ketoconazole or
systemic itraconazole, or chronic use of potent CYP3A4 inducers, such as
rifampicin.
[20] Are nursing or pregnant.
[21] Have a WHO functional class value of IV at the time of enrollment.
[22] Have severe hepatic cirrhosis, Child-Pugh Grade C.
[23] Have severe renal insufficiency, defined as receiving renal dialysis or having a measured or estimated creatinine clearance (CC) < 30 mL/min (Schwartz Formula):
All Females and Pre-adolescent Males:
Ccr (mL/min/1.73 m2) = 0.55 × Height (cm) / SCr (mg/dL)
Adolescent Males:
Ccr (mL/min/1.73 m2) = 0.70 × Height (cm) / SCr (mg/dL)
Where Ccr is Creatinine Clearance and SCr is Serum Creatinine
[24] Have severe hypotension or uncontrolled hypertension as determined by the Investigator.
[25] Diagnosed with a retinal disorder (for example, hereditary retinal disorders, retinopathy of the preterm and other retinal disorders)
[26] Have significant parenchymal lung disease.
[27] Have bronchopulmonary dysplasia.
[28] Have hemoglobinopathies.
[29] Have a history of drug, alcohol, or substance abuse within the past 6 months or present use, as assessed by the investigator.
[30] Have previously completed or withdrawn from this study (Study LVIG), or any other study investigating tadalafil.
[31] Have previously taken tadalafil within 90 days prior to the first
study drug dosing (Day 1, Visit 2) or are hypersensitive to tadalafil.
[32] Unable to take orally administered tablet (without chewing, crushing or breaking) or liquid su

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified