A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 or AMB-321 - Full Text View

Sponsored by:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00578786

Purpose

AMB-320/321-E has been designed to provide long-term, controlled monitoring of PAH patients treated with ambrisentan in order to properly define the adverse event profile associated with this ERA, including the incidence and severity of elevated serum LFTs. In addition, this study will continue the efficacy assessments of the previous studies, examine long-term ambrisentan treatment success, and compare long-term survival of subjects treated with ambrisentan to the NIH registry of patients with PAH.

Condition	Intervention	Phase
Pulmonary Arterial Hypertension	Drug: ambrisentan	Phase III

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Ambrisentan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 or AMB-321

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

The primary endpoint of this study is the incidence and severity of adverse events associated with long-term exposure to ambrisentan in subjects with PAH. [ Time Frame: long-term ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

1. A change from baseline in the: • Exercise capacity as measured by distance traveled in the six-minute walk test; • Borg Dyspnea Index immediately following exercise; • WHO Functional Class; • SF-36™ Health Survey; 2. Clinical worsenin [ Time Frame: long-term ] [ Designated as safety issue: Yes ]

Enrollment:	372
Study Start Date:	February 2004
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Ambrisentan: Experimental 2.5, 5 or 10 mg ambrisentan	Drug: ambrisentan 2.5, 5.0 or 10.0 mg ambrisentan po, qd, long-term

Detailed Description:

AMB-320 (ARIES-1) and AMB-321 (ARIES-2) were 12-week, Phase 3, randomized, double-blind, placebo-controlled, multicenter, efficacy studies of ambrisentan in subjects with pulmonary arterial hypertension (PAH). The objectives of these studies were to determine the effect of three doses of ambrisentan (2.5, 5.0, and 10.0 mg) on exercise capacity, as well as several clinical measures of PAH. The ARIES studies were identical except for the dose groups assessed and the geographic locations where the studies were conducted. Both studies evaluated placebo and 5.0 mg ambrisentan dose groups; however, AMB-320 also examined an ambrisentan dose of 10.0 mg, while AMB-321 included an ambrisentan dose of 2.5 mg. AMB-320/321-E is an optional study for subjects who have participated in AMB-320 or AMB-321 that will allow continued long-term treatment with ambrisentan.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject must have completed Week 12 of AMB-320 or AMB-321 or must have received placebo during AMB-320 or AMB-321 and met two or more early escape criteria;
Subject must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent form and must sign the form prior to the initiation of any study procedures.
Female subject of childbearing potential must agree to use two reliable methods of contraception until study completion and for at least four weeks following their final study visit. Reliable methods include: birth control pills/implants/injections, intrauterine devices (IUDs), spermicide, diaphragms, or condoms.

Exclusion Criteria:

Subjects must have met the exclusion criteria of the AMB-320 and AMB-321 studies. In addition, a subject who meets any one of the following criteria is ineligible for participation in the study:
1. Subject receiving bosentan, sildenafil, or iv inotropes at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit;
2. Subject receiving chronic prostanoid therapy (epoprostenol, treprostinil, iloprost, beraprost, or any other investigational prostacyclin derivative) within four weeks prior to the AMB-320/321-E Screening/RandomizationVisit;
3. Female subject who is pregnant or breastfeeding;
4. Subject with cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject;
5. Subject who has demonstrated noncompliance with previous medical regimens;
6. Subject who has a recent history of abusing alcohol or illicit drugs;
7. Subject who has participated in a clinical study involving another investigational drug or device at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578786

Locations

Argentina
Hospital Privado Centro Medico de Cordoba
Cordoba, Argentina, X5016KEH
Hospital Italiano de Cordoba
Cordoba, Argentina, X5004 FJE
Sanatorio Allende
Cordoba, Argentina, X5000JHQ
Instituto de Cardiologia J.F. Cabral
Corrientes, Argentina, W3400AMZ
Argentina, Buenos Aires
Clinica Independencia Munro
Munro, Buenos Aires, Argentina, 01605
Sanatorio Otamendi
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1115AAB
Instituto del Corazon Denton A. Cooley
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1416A
UAI Hosp. Universitario
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1437BZL
Hospital Britanico-Buenos Aires
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1280AEB
HIGA Hospital Interzonal General de Agudos Oscar Allende
Mar del Plata, Buenos Aires, Argentina, 07600
Argentina, Sante Fe
Hospital Italiano de Rosario
Rosario, Sante Fe, Argentina, 02000
Brazil
Hospital Madre Teresa
Belo Horizonte, Brazil, 30380-090
Hospital San Lucas de Pontificia Universidade Catolica
Porto Alegre, Brazil, 90610-000
Hospital das Clinicas da FMUSP
Sao Paulo, Brazil, 05403-000
Complexo Hospitalar Sanata Casa de Porto Alegre
Porto Alegre, Brazil, 92020-090
Universidade do Estado de Sao Paulo - UNIFESP
Sao Paulo, Brazil, 04023-062
Brazil, Rio de Janeiro
Hospital Universitario Clementino Fraga Filho
Ilha do Fundao, Rio de Janeiro, Brazil, 21941-590
Chile, Santiago de Chile
Hospital Clinico Universidad Catolica
Santiago, Santiago de Chile, Chile, CP 8350488
Hospital San Juan de Dios
Santiago, Santiago de Chile, Chile, CP 8330024
Instituto Nacional del Torax
Santiago, Santiago de Chile, Chile, CP7500691
Mexico, DF
Instituto Nacional de Cardiologia Ignacio Chavez
Mexico, DF, DF, Mexico, 14080
Mexico, Nuevo Leon
Unidad De Investigacion Clinica en Medicina
Monterrey, Nuevo Leon, Nuevo Leon, Mexico, 64718

Sponsors and Collaborators

Gilead Sciences

Investigators

Investigator:

Chris Dufton, PhD

Gilead Sciences

More Information

Responsible Party:	Gilead Sciences, Inc ( Chris Dufton, PhD )
Study ID Numbers:	AMB-320/321-E, ARIES-E
Study First Received:	December 19, 2007
Last Updated:	September 18, 2008
ClinicalTrials.gov Identifier:	NCT00578786
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Idiopathic pulmonary hypertension
Respiratory Tract Diseases
Hypertension, Pulmonary

Lung Diseases
Vascular Diseases
Hypertension

Additional relevant MeSH terms:

Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009