Currently no therapies are approved in the United States (US) for the treatment of children with pulmonary arterial hypertension (PAH). There is a growing body of evidence, however, supporting the use of therapies approved in the adult population with PAH, that has led to widespread off-label use in this pediatric population. There continues to be, however, a need for robust data to inform prescribing physicians regarding the safety and efficacy of all treatment options, including tadalafil, in the pediatric PAH population.
This is the first Phase 3 study of tadalafil for use in treating PAH in pediatric patients.
- 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 (6MW) distance from Baseline 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.
- For the European Union (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.
Period 2: 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.
Period 1: The secondary objectives of Period 1 are as follows:
- 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 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 pharmacokinetics (PK) of tadalafil in pediatric pulmonary arterial hypertension (PAH) patients.
- Assess the safety of tadalafil as compared with placebo.
Period 2: The secondary objective of Period 2 is to evaluate the incidence of, and time to CW.
Period 1: Additional objectives of Period 1 are as follows:
- Assess the efficacy of tadalafil compared with placebo on changes in World Health Organization (WHO) functional classification.
- Explore by cardiac magnetic resonance imaging (MRI), changes from Day 1 to Week 24 in the following cardiac MRI parameters:
- left-ventricular (LV) ejection fraction
- right-ventricular (RV) end diastolic volume
- RV end systolic volume
- RV ejection fraction
- Evaluate by echocardiography, changes from Day 1 to Week 24 in the following echocardiographic parameters:
- tricuspid annular plane systolic excursion (TAPSE)
- eccentricity index, pericardial effusion
- maximal tricuspid regurgitant velocity
Assess physician and caregiver-reported health outcome, as measured by Clinical Global Impression of Improvement (CGI-I), and in a subset of patients ≥5 years of age, Child Health Questionnaire Parent Form 28 (CHQ-PF28).
Evaluate change from Day 1 to Week 24 in N-terminal prohormone brain natriuretic peptide (NT-Pro-BNP) concentrations
Principal Investigator: Ronald Day
Department: Pediatric Administration