Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529

NCT ID: NCT01342952

Last Updated: 2022-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-21
• Study Completion Date: 2022-06-09

Brief 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).

Conditions

Hypertension, Pulmonary

Keywords

pulmonary arterial hypertension; pediatrics

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ambrisentan

Open label, flexible dosing from 2.5 mg to 10 mg (not to exceed 0.25 mg/kg) per day

Group Type: EXPERIMENTAL

Ambrisentan

Intervention Type: DRUG

open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day

Interventions

Ambrisentan

open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have participated in and complied, to the best of their ability, with the protocol for AMB112529 and have met one of the following:

1. Completed the Week 24 visit in AMB112529;

2. Required additional targeted treatment for PAH due to inadequate response to the current treatment or worsening of their clinical condition prior to week 24 in AMB112529;

3. Required reduction in dose of baseline targeted treatment for PAH after ambrisentan was added to the treatment regimen;

4. In the opinion of the investigator, continued treatment with ambrisentan is warranted.

• A female is eligible to participate in this study, as assessed by the investigator, if she is of:

1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or,

2. Child-bearing potential - has a negative pregnancy test and is not lactating and, if sexually active, agrees to continue to use 2 reliable methods of contraception 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).

• 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.

Exclusion Criteria

• Subjects who were withdrawn from ambrisentan in Study AMB112529;
• Subjects who did not comply with the protocol in Study AMB112529;
• Female subjects who are pregnant or breastfeeding;
• Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min assessed within the previous 45 days) at the point of transition from Study AMB112529 into this study;
• Subject with clinically significant fluid retention in the opinion of the investigator;
• Subject with clinically significant anaemia in the opinion of the investigator;
• Subjects who are to enter another clinical trial or be treated with another investigational product after exiting Study AMB112529.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Aurora, Colorado, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Ann Arbor, Michigan, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Guymallen, Mendoza Province, Argentina

GSK Investigational Site

Ciudad de Buenos Aires, , Argentina

GSK Investigational Site

Córdoba, , Argentina

GSK Investigational Site

Paris, , France

GSK Investigational Site

Pessac, , France

GSK Investigational Site

Toulouse, , France

GSK Investigational Site

Giessen, Hesse, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

San Donato Milanese (MI), Lombardy, Italy

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Kemerovo, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Madrid, , Spain

Countries

Brazil; Canada; Mexico; Netherlands; United States; Argentina; France; Germany; Hungary; Italy; Japan; Russia; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2010-021572-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

114588

Identifier Type: -

Identifier Source: org_study_id