Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Serious Adverse Events [ Time Frame: up to 18 years of age ]Number of patients with a serious adverse event
- Adverse Events [ Time Frame: up to 18 years of age ]Number of patients with adverse events
- Liver Function Tests [ Time Frame: up to 18 years of age ]AST, ALT, GGT, and total bilirubin
- Clinical Chemistries [ Time Frame: up to 18 years of age ]sodium, magnesium, potassium, calcium, glucose, chloride, bicarbonate, phosphorus-inorganic, creatinine, total protein, albumin, LDH, creatine phosphokinase, blood urea nitrogen, uric acid, and alkaline phosphatase
- Haematology [ Time Frame: up to 18 years of age ]platelet count, RBC count, reticulocyte count, hematocrit, hemoglobin, RBC indices (MVC, MCH, and MCHC), WBC count, and automated WBC differential
- Physical examination [ Time Frame: up to 18 years of age ]Change from baseline from Study AMB112529 in physical parameters
- Vital signs [ Time Frame: up to 18 years of age ]Change from baseline from Study AMB112529 in blood pressure, respiratory rate, and heart rate
- 12-lead ECG [ Time Frame: up to 18 years of age ]Change from baseline from Study AMB112529
- Endocrinology assessments [ Time Frame: up to 20 years of age ]FSH, LH, sex hormone binding globulin, inhibin B, testosterone (males only) and estrogen (females only)
- Pubertal Development [ Time Frame: up to 20 years of age ]Assessed using Tanner criteria. Testicular volume will be estimated in males using Prader's orchidometer
- 6 minute walk distance [ Time Frame: up to 18 years of age ]Change from baseline from study AMB112529 in the distance walked in six minutes
- WHO functional class [ Time Frame: up to 18 years of age ]Change from baseline from study AMB112529 i nWHO functional class
- Health outcomes assessments [ Time Frame: up to 18 years of age ]Change from baseline from study AMB112529 in SF 10 and the proportion of days missed from school due to symptoms of the disease
- Echocardiogram [ Time Frame: up to 18 years of age ]Pericardial effusion, right atrial pressure, tricuspid annular plane systolic excursion, eccentricity index (systolic and diastolic), and right ventricular pressure by tricuspid regurgitant jet velocity
- Plasma NT-Pro-BNP [ Time Frame: up to 18 years of age ]Change from baseline from study AMB112529 in plasma NT-Pro BNP
- Time to clinical worsening [ Time Frame: up to 18 years of age ]The time from randomization in study AMB112529 until the first occurence of: death (all cause) or placed on active list for lung transplant; hospitalisation due to PAH deterioration; addition or increased dose of other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition; atrial septostomy; or PAH related deterioration (increase in WHO functional class, deterioration in exercise testing, clinical signs of symptoms of right sided heart failure)
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||October 2024|
|Estimated Primary Completion Date:||October 2022 (Final data collection date for primary outcome measure)|
Open label, flexible dosing from 2.5 mg to 10 mg (not to exceed 0.25 mg/kg) per day
open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01342952
|Contact: US GSK Clinical Call Center||877-379-3718||GSKClinicalSupportHD@gsk.com|
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|Study Director:||GSK Clinical Trials||GlaxoSmithKline|