Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
Condition: Hypertension, Pulmonary
MeSH terms: Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hypertension
Study type: Interventional
Phase: Phase 2

Summary: 
      An open label, long term extension to Study AMB112529. All subjects may remain in the
      extension study for a minimum of six months. Beyond the six month period, subjects may
      continue in the extension study until one of the following conditions is met:

      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
      paediatric 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).

      The primary objective is the long-term safety and tolerability of ambrisentan in the
      paediatric PAH population. Secondary objectives are all cause mortality and change from
      baseline in Study AMB112529 on efficacy parameters.
    

Detailed description: 
      Pulmonary arterial hypertension (PAH) is a rare, progressive, highly debilitating disease
      characterized by vascular obstruction and the variable presence of vasoconstriction, leading
      to increased pulmonary vascular resistance and right-sided heart failure. If left untreated,
      PAH ultimately leads to right ventricular failure and death; adult subjects have a median
      survival of 2.8 years without treatment. Epidemiological estimates vary but prevalence in
      Europe is thought to be of the order of 15 cases per million. Large scale epidemiology
      studies of PAH in children have not been conducted and there is no or limited outcome data in
      paediatric PAH patients. A register in France (1995-1996) estimates the prevalence in
      children is as low as 3.7 cases per million. In a national, comprehensive country wide survey
      of the epidemiology of idiopathic PAH (IPAH) management and survival in the United Kingdom
      (UK) the incidence was 0.48 cases per million children per year and the prevalence was 2.1
      cases per million children.

      Ambrisentan (VOLIBRIS™ tablets) is an endothelin receptor antagonist (ERA) marketed in the
      European Union (EU) and some other countries by GlaxoSmithKline (GSK) and in the United
      States as LETAIRIS® by Gilead Sciences Inc. Ambrisentan is indicated for the treatment of
      adult patients with PAH to improve exercise capacity, decrease the symptoms of PAH, and delay
      clinical worsening.

      The primary purpose of this long term paediatric study is to provide clinically relevant
      information on the long term safety of ambrisentan in children with the most common causes of
      PAH in this age group. This study is only open to patients who have participated in Study
      AMB112529, 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, and in whom
      continued treatment with ambrisentan is warranted.

      This study is part of a Paediatric Investigational Plan (PIP; EMEA-000434-PIP01-08) agreed
      with the European Medicines Agency's Paediatric Committee (PDCO).
    

Intervention name(s): Ambrisentan
Intervention type(s): Drug
Intervention description(s): open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day
Intervention MeSH terms: Ambrisentan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: pulmonary arterial hypertension; pediatrics