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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01342952
First received: April 26, 2011
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Hypertension, Pulmonary
Drug: Ambrisentan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Seirous Adverse Events [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: Yes ]
    Number of patients with a serious adverse event

  • Adverse Events [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: Yes ]
    Number of patients with adverse events

  • Liver Function Tests [ Time Frame: When Patient reaches 18 years of age ] [ Designated as safety issue: Yes ]
    AST, ALT, GGT, and total bilirubin

  • Clinical Chemistries [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: Yes ]
    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: When patient reaches 18 years of age ] [ Designated as safety issue: Yes ]
    platelet count, RBC count, reticulocyte count, hematocrit, hemoglobin, RBC indices (MVC, MCH, and MCHC), WBC count, and automated WBC differential

  • Physical examination [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: Yes ]
    Change from baseline from Study AMB112529 in physical parameters

  • Vital signs [ Time Frame: Shen patient reaches 18 years of age ] [ Designated as safety issue: Yes ]
    Change from baseline from Study AMB112529 in blood pressure, respiratory rate, and heart rate

  • 12-lead ECG [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: Yes ]
    Change from baseline from Study AMB112529

  • Endocrinology assessments [ Time Frame: When patient reaches 20 years of age ] [ Designated as safety issue: Yes ]
    FSH, LH, sex hormone binding globulin, inhibin B, testosterone (males only) and estrogen (females only)

  • Pubertal Development [ Time Frame: When patient reaches 20 years of age ] [ Designated as safety issue: Yes ]
    Assessed using Tanner criteria. Testicular volume will be estimated in males using Prader's orchidometer


Secondary Outcome Measures:
  • 6 minute walk distance [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: No ]
    Change from baseline from study AMB112529 in the distance walked in six minutes

  • WHO functional class [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: No ]
    Change from baseline from study AMB112529 i nWHO functional class

  • Health outsomes assessments [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: No ]
    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: When patient reaches 18 years of age ] [ Designated as safety issue: No ]
    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: When patient reaches 18 years of age ] [ Designated as safety issue: No ]
    Change from baseline from study AMB112529 in plasma NT-Pro BNP

  • Time to clinical worsening [ Time Frame: When patient reaches 18 years of age ] [ Designated as safety issue: No ]
    The time from randomization in study AMB112529 until the first occurance 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 derterioration of clinical condition; atrial septostomy; or PAH related deterioration (increase in WHO functional class, deterioration in exercise testing, clinical sighns of symptoms of right sided heart failure)


Estimated Enrollment: 66
Study Start Date: June 2011
Estimated Study Completion Date: December 2024
Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ambrisentan
Open label, flexible dosing from 2.5 mg to 10 mg (not to exceed 0.25 mg/kg) per day
Drug: Ambrisentan
open label, flexible dosing from 2.5 to 10 mg (not to exceed 10 mg/kg) per day

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).

  Eligibility

Ages Eligible for Study:   8 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01342952

Contacts
Contact: US GSK Clinical Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Hide Study Locations
Locations
United States, California
GSK Investigational Site Terminated
Palo Alto, California, United States, 94304-1601
United States, Colorado
GSK Investigational Site Recruiting
Aurora, Colorado, United States, 80045
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, Massachusetts
GSK Investigational Site Recruiting
Boston, Massachusetts, United States, 02115
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, Michigan
GSK Investigational Site Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, New York
GSK Investigational Site Recruiting
New York, New York, United States, 10032
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Argentina
GSK Investigational Site Recruiting
Guymallen, Mendoza, Argentina, 5521
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Ciudad de Buenos Aires, Argentina, 1118
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Terminated
Corrientes, Argentina, W3400AMZ
GSK Investigational Site Recruiting
Córdoba, Argentina, 5000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Canada, Ontario
GSK Investigational Site Terminated
Toronto, Ontario, Canada, M5G 1X8
France
GSK Investigational Site Recruiting
Paris cedex 15, France, 75743
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Pessac cedex, France, 33604
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Toulouse cedex 9, France, 31059
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Germany
GSK Investigational Site Terminated
Erlangen, Bayern, Germany, 91054
GSK Investigational Site Recruiting
Giessen, Hessen, Germany, 35385
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Berlin, Germany, 13353
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Hungary
GSK Investigational Site Recruiting
Budapest, Hungary, 1096
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Italy
GSK Investigational Site Recruiting
Roma, Lazio, Italy, 00165
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
San Donato Milanese (MI), Lombardia, Italy, 20097
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Japan
GSK Investigational Site Not yet recruiting
Kanagawa, Japan, 232-8555
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Osaka, Japan, 565-0871
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Tokyo, Japan, 143-8541
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Tokyo, Japan, 104-8560
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Russian Federation
GSK Investigational Site Recruiting
Kemerovo, Russian Federation, 650002
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Moscow, Russian Federation, 125412
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Novosibirsk, Russian Federation, 630055
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Spain
GSK Investigational Site Terminated
Barcelona, Spain, 08035
GSK Investigational Site Recruiting
Madrid, Spain, 28034
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Completed
Madrid, Spain, 28046
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01342952     History of Changes
Other Study ID Numbers: 114588
Study First Received: April 26, 2011
Last Updated: August 21, 2014
Health Authority: Italy: Comitato Etico Azienda Ospedaliero-Universitaria di Bologna
Spain: Agencia Española del Medicamento y Productos Sanitarios
Hungary: National Institute of Pharmacy
United States: Food and Drug Administration
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Netherlands: Medicines Evaluation Board (MEB)
Japan: Pharmaceuticals and Medical Devices Agency
Greece: National Drug Organisation

Keywords provided by GlaxoSmithKline:
pulmonary arterial hypertension
pediatrics

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on October 21, 2014