A randomized, open label study comparing safety and efficacy parameters for a high and a low dose of ambrisentan (adjusted for body weight) for the treatment of pulmonary arterial hypertension in paediatric patients aged 8 years up to 18 years - AMB112529
- Conditions
- pulmonary arterial hypertension (PAH)MedDRA version: 9.1Level: LLTClassification code 10064911MedDRA version: 9.1Level: LLTClassification code 10065150MedDRA version: 9.1Level: LLTClassification code 10065151MedDRA version: 9.1Level: LLTClassification code 10065152
- Registration Number
- EUCTR2010-019547-19-IT
- Lead Sponsor
- GlaxoSmithKline Research & Development, Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 66
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 na?ve, 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.
Complete information regarding warnings, precautions, contraindications, adverse events,
and other pertinent information on the investigational product that may impact subject
eligibility is provided in the Investigators Brochure and product label.
Are the trial subjects under 18? yes
Number of subjects for this age range:
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
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
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method