An open-label, long term extension study for treatment of pulmonary arterial hypertension in paediatric patients aged 8 years up to 18 years who have participated in AMB112529 and in whom continued treatment with ambrisentan is desired (AMB114588)

Pulmonary arterial hypertension (PAH) is a life threatening disease,
characterized by a serious persistent increase of PA pressure. This results in
right ventricular failure and death.
There are various treatment options, but no single drug is effective for all
patients. Morbidity and mortality is high among patients with PAH, who remain
symptomatic despite treatment.
Ambrisentan is a endothelin receptor antagonist (ERA). It targets the ETA
receptor and blocks the undesired effects if the vasoconstrictive endothelin-1.
The drug has been regsitered under the name Volibris for the treatment of
adults with PAH.
Except bosentan no drugs have been regstred for the treatment of adolescents or
children, but they are frequently used off-label. In line with the current
opinion, the sponsor would like to collect structured data on the effects of
ambrisentan in youngsters.
This is an extension study of the study AMB112529, that has been designed to
collect data on efficacy, safety and PK of 2 dosages of ambrisentan in minors
as of the age of 8 with PAH. The purpose of this extension study is to collect
longterm safety and tolerability data and, on the other hand, to enable
participants to continue with ambrisentan until the drug has been registered
for the treatment of people under 18 years of age.

Primary: Longterm safety and tolerability of 2 dosages of ambrisentan.
Secundary: Supportive efficacy data.

Multicenter open label non-comparative phase III study.
Treatment with ambrisentan in a dose to be determined by the investigator.
Minimal duration 6 months. Thereafter continuation is possible until
* The subject turns 18 years of age (when the subject can receive marketed
product);
* The product is approved and available for use in the subject*s age group;
* Development for use in the pediatric population is discontinued;
* The subject decides he/she no longer wants to participate in the study;
* The investigator considers it is in the best interest of the subject to
discontinue ambrisentan (e.g. for safety reasons).
Max. 66 patients.

Treatment with ambrisentan.

Risk: Adverse events of study medication.
Burden: Monthly blood tests (2.5-3.5 ml/visit) and pregnancy test (if
relevant). Visit to investigator every 3 months. Duration 1-3 h.
Every 3 months: SF-10 questionnaire.
Every 6 months: physical examination, ECG, echocardiogram, 6 min. walk test.
Extra in comparison to regular care: longer (1-2 h) hospital visits, possibly
somewhat more frequent blood tests. 6 min. walk test, pregnancy test and
questionnaire: in most cases only because of study participation.