Pulmonary Arterial Hypertension MedDRA version: 15.1 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: [1] =6 months to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: [1] Pulmonary hypertension related to conditions other than specified in inclusion criteria. [2] 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 (i.e., 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. [3] History of atrial septostomy or Potts Shunt within 3 months before administration of study drug. [4] Unrepaired congenital heart disease. [5] History of angina pectoris or other condition that was treated with long- or short-acting nitrates within 12 weeks before administration of study drug. [6] WHO functional class value of either I or IV at the time of screening. [7] Severe hepatic impairment, Child-Pugh Grade C. [8] Severe renal insufficiency, defined as receiving renal dialysis or having a measured or estimated creatinine clearance (CC) < 30 mL/min (Schwartz Formula) [9] Retinal disorder (e.g., hereditary retinal disorders, retinopathy of the preterm patient and other retinal disorders) [10] Severe hypotension or uncontrolled hypertension as determined by the Investigator. [11] Significant parenchymal lung disease. [12] Bronchopulmonary dysplasia. [13] Concurrent PDE5 inhibitor therapy (sildenafil or vardenafil) or has received PDE5 inhibitor therapy within 24 hours prior to the first study drug dosing. [14] Concurrent therapy with prostacyclin or its analogues. [15] Previously completed or withdrawn from this study (LVHV), or any other study investigating tadalafil. [16] Commenced or discontinued a chronic PAH medication including but not restricted to: calcium channel blockers, diuretics, anti-coagulants, digoxin, and oxygen therapy within four weeks of screening. [17] Currently receiving treatment with doxazosin, nitrates, or cancer therapy. [18] 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. [19] History of loss of vision in 1 eye because of nonarteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous phosphodiesterase type 5 (PDE5) inhibitor exposure.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Period 1 primary objectives: For the EU regulatory assessment, the primary objective of Period 1 is to evaluate the efficacy of tadalafil compared with placebo, as measured by time to clinical worsening (CW) in pediatric PAH patients through Week 24. For the United States (US) regulatory assessment, the primary objective of Period 1 is to evaluate the efficacy of tadalafil compared with placebo in improving 6-minute walk distance from bBaseline to Week-24 as assessed in a subset of patients =6 to <18 years of age who are developmentally capable of performing a 6MW test. Period 2 Primary Objective: The primary objective of Period 2 is to evaluate long-term safety of tadalafil while providing continued access to tadalafil for pediatric patients with PAH who participated in Period 1;Secondary Objective: Period 1 secondary objectives: • Assess the efficacy of tadalafil compared with placebo on time to CW (for the US regulatory assessment) and the incidence of CW. • Assess the efficacy of tadalafil compared with placebo on 6-minute walk (6MW) distance in a subset of patients =6 to <18 years of age who are developmentally capable of performing a 6MW test (for the EU regulatory assessment). • Characterize the population PK of tadalafil in pediatric PAH patients. • Assess the safety of tadalafil compared with placebo. Period 2 secondary objectives: • The secondary objective of Period 2 is to evaluate the incidence of, and time to CW;Primary end point(s): For the EU regulatory assessment, the primary endpoint for this study is time to first occurrence of clinical worsening. For the US regulatory assessment, the primary endpoint for this study is 6 minute-walk distance in meters assessed in a subset of patients =6 to <18 years of age who are developmentally capable of performing a 6MW test.;Timepoint(s) of evaluation of this end point: For time to first occurrence of clinical worsening -throughout the duration of the study. For 6 minute-walk distance in | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Period 1 •Time to clinical worsening (for the US regulatory assessment) and the incidence of clinical worsening •6 minute walk (MW) distance in meters measured in subset of patients who are =6 to <18 years of age and who are developmentally capable of performing a 6MW test (for the EU regulatory assessment). •Population PK assessment of plasma tadalafil concentrations at steady-state. Period 2 •Incidence of and time to clinical worsening •6MW distance in meters measured in subset of patients who are =6 to <18 years of age and who are developmentally capable of performing a 6MW test. ;Timepoint(s) of evaluation of this end point: For clinical worsening -throughout the duration of the study. For 6 minute-walk distance in meters day 1, weeks 4, 8,12,16, 20, 24,1 year and 2 year. For PK assessment - at weeks 2, 4, 16 and 24. | — |
Countries
Austria, Belgium, Brazil, Canada, France, Germany, Italy, Japan, Mexico, Netherlands, Poland, Romania, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Eli Lilly
Outcome results
None listed