Testing medicines to treat children with pulmonary arterial hypertension(PAH)

• Conditions: Pulmonary Arterial Hypertension; MedDRA version: 14.1Level: LLTClassification code 10065150Term: Associated with pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 14.1Level: LLTClassification code 10065151Term: Idiopathic pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 14.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 14.1Level: LLTClassification code 10065152Term: Familial pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2010-019547-19-Outside-EU/EEA
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-03-16
• Last Update Posted: 21 August 2012

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 66

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
• 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 <3 x Upper Limit of Normal (ULN).
6. A female is eligible to participate in this study, as assessed by the investigator, if she is of: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or, b. Child-bearing potential - has a negative pregnancy test and is not lactating at the Screening and Baseline/Randomisation Visits and, if sexually active, agrees to use 2 reliable methods of contraception from the Screening Visit until study completion and for at least 30 days following the last dose of study drug (reliable methods of contraception are listed in Appendix 2).
7. Subject or subject’s legal guardian is able and willing to give written informed consent. As part of the consent, female subjects of childbearing potential will be informed of the risk of teratogenicity and will need to be counselled in a developmentally appropriate manner on the importance of pregnancy prevention; and male subjects will need to be informed of potential risk of testicular tubular atrophy and aspermia.
Are the trial subjects under 18? yes
Number of subjects for this age range: 66
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

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 antigen 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.

Study & Design

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