Pulmonary Arterial Hypertension MedDRA version: 14.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Pediatric patients (?6 months to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 atrial septostomy or Potts Shunt within 3 months before administration of study drug. [13] Unrepaired congenital heart disease except associated with an atrial-ventricular septal defect. [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 antiretroviral therapy (protease inhibitor), systemic ketoconazole or systemic itraconazole. [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 or are hypersensitive to tadalafil. [32] Unable to take orally administered tablet (without chewing, crushing or breaking) or liquid suspension. [33] Investigator site personnel (or their immediate family) directly affiliated with this study. Immediate family i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective of the trial is to characterize the pharmacokinetics (PK) of tadalafil in a pediatric population with pulmonary arterial hypertension (PAH) to establish an appropriate dose range for further clinical research.;Secondary Objective: Secondary Objectives: - To assess the tolerability and safety of tadalafil in a pediatric population with PAH. - To compare tadalafil PK profile in a pediatric population with historical adult data from Study H6D-MC-LVGY. - To assess the palatability of the tadalafil suspension. Open-label Extension Objective (Period 2): - To evaluate long-term safety while providing continued access to tadalafil for pediatric patients completing Period 1. - To evaluate clinical worsening (CW), defined as any of the following: death, lung or heart transplantation, atrial septostomy or potts shunt, hospitalization due to worsening PAH, new onset syncope, initiation of new PAH therapy, worsening of World Health Organization (WHO) functional class by 1 or more, and decreasing of 20% in the 6-minute walk (6MW) test (for those patients ?7 years of age).;Primary end point(s): Safety: Safety will be evaluated using spontaneously reported adverse events, clinical laboratory data, vital signs, physical examinations, and centralized 12-lead electrocardiograms (ECGs) as outlined in the schedule of events. Bioanalytical: Plasma concentrations of tadalafil. Pharmacokinetic/Pharmacodynamic: The pharmacokinetic parameters estimated during analysis will include area under the concentration-time curve (AUC), maximal concentration (Cmax), time of Cmax (tmax), apparent clearance (CL/F), apparent volume of distribution (Vz/F), and terminal half-life (t½), as appropriate.;Timepoint(s) of evaluation of this end point: Throughout the duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NA;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Canada, France, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Eli Lilly
Outcome results
None listed