Pulmonary Arterial Hypertension MedDRA version: 12.1 Level: LLT Classification code 10064911 Term: Pulmonary arterial hypertension MedDRA version: 12.1 Level: LLT Classification code 10065150 Term: Associated with pulmonary arterial hypertension MedDRA version: 12.1 Level: LLT Classification code 10065151 Term: Idiopathic pulmonary arterial hypertension MedDRA version: 12.1 Level: LLT Classification code 10065152 Term: Familial pulmonary arterial hypertension MedDRA version: 12.1 Level: PT
Conditions
Sponsors
GlaxoSmithKline Research & Development, Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female at least 8 years of age and not yet 18 years of age at the time of randomization. 2. A current diagnosis of PAH (WHO Group 1) with WHO class II or III symptoms in one of the following categories: • Idiopathic • Heritable [familial] • Secondary to connective tissue disease (e.g., limited scleroderma, diffuse scleroderma, mixed connective tissue disease (CTD), systemic lupus erythematosus, or overlap syndrome). • Persistent PAH despite surgical repair (at least 6 months prior to the screening visit) of atrial septal defects, ventricular septal defects, atrio-ventricular septal defects, and persistent patent ductus. 3. Have met the following hemodynamic criteria for subjects with right heart catheterization (RHC) when performed as part of the diagnosis or routine care (see Appendix 1): • mean pulmonary arterial pressure (mPAP) of ?25 mmHg • pulmonary vascular resistance (PVR) of ?240 dyne?sec/cm5 • left ventricular end diastolic pressure (LEVDP) or pulmonary capillary wedge pressure (PCWP) of =15 mmHg. 4. Subjects must either be treatment naïve, have discontinued treatment with another ERA (e.g., bosentan) at least 1 month previously because of elevated liver function tests (LFTs), or have been on a stable dose of drug therapy for PAH (e.g., sildenafil or prostacyclin) for at least one month prior to the Screening Visit. The baseline drug therapy for PAH, if any, should not change from the Screening Visit until the end of all Treatment Period assessments. 5. Subjects who discontinued ERA treatment due to elevated LFTs, must have LFTs of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects currently taking an ERA. 2. Subjects currently taking cyclosporine A. 3. Subjects whose body weight is less than 20 Kg. 4. Subjects who have not tolerated PAH therapy due to adverse effects which may be related to their mechanism of action (e.g., prostanoids, ERA, PDE-5 inhibitors) with the exception of liver abnormalities for those subjects who were receiving another ERA. 5. Female subjects who are pregnant or breastfeeding. 6. Subjects with diagnosis of active hepatitis (hepatitis B surface antibody and hepatitis C antibody), or clinically significant hepatic enzyme elevation (i.e., ALT, AST or AP >3xULN) at Screening. 7. Subjects with severe renal impairment (creatinine clearance <30 mL/min) at Screening. 8. Subject has clinically significant fluid retention in the opinion of the investigator. 9. Subject has clinically significant anaemia in the opinion of the investigator. 10. Subject has a known hypersensitivity to the study drug, the metabolites, or formulation excipients. 11. Subjects who have participated in another trial or have taken another investigational product during the previous 30 days. 12. Alcohol abuse, illicit drug use within 1 year. 13. Any concurrent condition or concurrent use of medication that would affect subject safety in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is the safety and tolerability of ambrisentan in the paediatric PAH population.;Secondary Objective: Pharmcokinetics: • Population pharmacokinetic assessment based on one plasma sample per subject at Weeks 4 (trough), 8 (0.5 to 4 hours post-dose), 12 (trough), 16 (0.5 to 4 hours post-dose), 20 (4 to 22 hours post-dose), and 24 (trough). •Pharmacokinetic/pharmacodynamic modelling. Efficacy • The change from baseline in the 6 minute walking distance (6MWD) test evaluated after 24 weeks of therapy. • Mean changes from baseline in the 6MWD test at Weeks 4, 8, 12, 16, and 20. • The time to clinical worsening of PAH. • The change from baseline in Subject Global Assessment to Week 24 using the SF- 10 health survey for children. • The change from baseline in WHO functional class to Week 24. • Change from baseline in plasma N-Terminal pro-B-type Natriuretic Peptide (NT-Pro BNP) concentration at Week 24. ;Primary end point(s): Safety as assessed by: • Adverse Events. • Serious Adverse Events. • Clinical laboratory parameters. • Physical examination (Including height, weight, body mass index / body surface area, oxygen saturation, jugular venous pressure, liver size, and presence of peripheral oedema and/or ascites.) • Vital Signs. • Pubertal development (change from baseline in endocrinology assessments at Weeks 12 and 24). | — |
Countries
France, Germany, Greece, Hungary, Italy, Netherlands, Spain
Outcome results
None listed