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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01342952
Recruitment Status : Active, not recruiting
First Posted : April 27, 2011
Last Update Posted : March 23, 2020
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Hypertension, Pulmonary Drug: Ambrisentan Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : June 21, 2011
Estimated Primary Completion Date : June 11, 2022
Estimated Study Completion Date : June 11, 2024

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Serious Adverse Events [ Time Frame: up to 18 years of age ]
    Number of patients with a serious adverse event

  2. Adverse Events [ Time Frame: up to 18 years of age ]
    Number of patients with adverse events

  3. Liver Function Tests [ Time Frame: up to 18 years of age ]
    AST, ALT, GGT, and total bilirubin

  4. 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

  5. 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

  6. Physical examination [ Time Frame: up to 18 years of age ]
    Change from baseline from Study AMB112529 in physical parameters

  7. Vital signs [ Time Frame: up to 18 years of age ]
    Change from baseline from Study AMB112529 in blood pressure, respiratory rate, and heart rate

  8. 12-lead ECG [ Time Frame: up to 18 years of age ]
    Change from baseline from Study AMB112529

  9. 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)

  10. 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

Secondary Outcome Measures :
  1. 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

  2. WHO functional class [ Time Frame: up to 18 years of age ]
    Change from baseline from study AMB112529 i nWHO functional class

  3. 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

  4. 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

  5. Plasma NT-Pro-BNP [ Time Frame: up to 18 years of age ]
    Change from baseline from study AMB112529 in plasma NT-Pro BNP

  6. 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)

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   8 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01342952

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United States, Colorado
GSK Investigational Site
Aurora, Colorado, United States, 80045
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02115
United States, Michigan
GSK Investigational Site
Ann Arbor, Michigan, United States, 48109-4204
United States, New York
GSK Investigational Site
New York, New York, United States, 10032
GSK Investigational Site
Guymallen, Mendoza, Argentina, 5521
GSK Investigational Site
Ciudad de Buenos Aires, Argentina, 1118
GSK Investigational Site
Córdoba, Argentina, 5000
GSK Investigational Site
Paris cedex 15, France, 75743
GSK Investigational Site
Pessac cedex, France, 33604
GSK Investigational Site
Toulouse cedex 9, France, 31059
GSK Investigational Site
Giessen, Hessen, Germany, 35385
GSK Investigational Site
Berlin, Germany, 13353
GSK Investigational Site
Budapest, Hungary, 1096
GSK Investigational Site
Roma, Lazio, Italy, 00165
GSK Investigational Site
San Donato Milanese (MI), Lombardia, Italy, 20097
GSK Investigational Site
Osaka, Japan, 565-0871
GSK Investigational Site
Tokyo, Japan, 104-8560
GSK Investigational Site
Tokyo, Japan, 143-8541
Russian Federation
GSK Investigational Site
Kemerovo, Russian Federation, 650002
GSK Investigational Site
Moscow, Russian Federation, 125412
GSK Investigational Site
Novosibirsk, Russian Federation, 630055
GSK Investigational Site
Madrid, Spain, 28046
Sponsors and Collaborators
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Study Director: GSK Clinical Trials GlaxoSmithKline

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Responsible Party: GlaxoSmithKline Identifier: NCT01342952    
Other Study ID Numbers: 114588
2010-021572-29 ( EudraCT Number )
First Posted: April 27, 2011    Key Record Dates
Last Update Posted: March 23, 2020
Last Verified: March 2020
Keywords provided by GlaxoSmithKline:
pulmonary arterial hypertension
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Antihypertensive Agents