A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202)

NCT ID: NCT00578786

Last Updated: 2013-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 383 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2010-03-31

Brief Summary

AMB-320/321-E was designed to provide long-term, controlled monitoring of pulmonary arterial hypertension (PAH) patients treated with ambrisentan (AMB) in order to properly define the adverse event profile associated with this endothelin receptor antagonist (ERA), including the incidence and severity of elevated serum liver function tests (LFTs). In addition, this study continued the efficacy assessments of the previous studies, examined long-term AMB treatment success, and compared long-term survival of subjects treated with AMB to the NIH registry of patients with PAH.

Detailed Description

AMB-320 (ARIES-1; NCT00423748) and AMB-321 (ARIES-2; NCT00423202) were 12-week, Phase 3, randomized, double-blind, placebo-controlled, multicenter, efficacy studies of AMB in subjects with PAH. The objectives of these studies were to determine the effect of three doses of AMB (2.5, 5.0, and 10.0 mg) on exercise capacity, as well as several clinical measures of PAH. The current study (NCT00578786) was unblinded (by design) prior to completion. 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 AMB dose groups; however, AMB-320 (NCT00423748) also examined an AMB dose of 10.0 mg, while AMB-321 (NCT00423202) included an AMB dose of 2.5 mg. AMB-320/321-E was an optional study for subjects who had participated in AMB-320 (NCT00423748) or AMB-321 (NCT00423202) that allowed continued long-term treatment with AMB.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Ambrisentan

2.5, 5 or 10 mg ambrisentan

Group Type: EXPERIMENTAL

ambrisentan

Intervention Type: DRUG

2.5, 5.0 or 10.0 mg ambrisentan po, qd, long-term

Interventions

ambrisentan

2.5, 5.0 or 10.0 mg ambrisentan po, qd, long-term

Intervention Type: DRUG

Other Intervention Names

Letairis(TM)

Eligibility Criteria

Inclusion Criteria

1. Subject must have completed Week 12 of AMB-320 (NCT00423748) or AMB-321 (NCT00423202) or must have received placebo during AMB-320 (NCT00423748) or AMB-321 (NCT00423202) and met two or more early escape criteria;

2. 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.

3. 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

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.

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

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chris Dufton, PhD

Role: STUDY_CHAIR

Gilead Sciences

Locations

Sanatorio Otamendi

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Hospital Britanico-Buenos Aires

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Instituto del Corazon Denton A. Cooley

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

UAI Hosp. Universitario

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

HIGA Hospital Interzonal General de Agudos Oscar Allende

Mar del Plata, Buenos Aires, Argentina

Clinica Independencia Munro

Munro, Buenos Aires, Argentina

Instituto de Cardiologia J.F. Cabral

Corrientes, Corrientes Province, Argentina

Sanatorio Allende

Córdoba, Córdoba Province, Argentina

Hospital Italiano de Cordoba

Córdoba, Córdoba Province, Argentina

Hospital Italiano de Rosario

Rosario, Sante Fe, Argentina

Hospital Privado Centro Medico de Cordoba

Córdoba, , Argentina

Hospital Universitario Clementino Fraga Filho

Ilha Do Fundao, Rio de Janeiro, Brazil

Hospital Madre Teresa

Belo Horizonte, , Brazil

Hospital San Lucas de Pontificia Universidade Catolica

Porto Alegre, , Brazil

Complexo Hospitalar Sanata Casa de Porto Alegre

Porto Alegre, , Brazil

Universidade do Estado de Sao Paulo - UNIFESP

São Paulo, , Brazil

Hospital das Clinicas da FMUSP

São Paulo, , Brazil

Hospital San Juan de Dios

Santiago, Santiago de Chile, Chile

Hospital Clinico Universidad Catolica

Santiago, Santiago de Chile, Chile

Instituto Nacional del Torax

Santiago, Santiago de Chile, Chile

Instituto Nacional de Cardiologia Ignacio Chavez

Mexico City, Mexico City, Mexico

Unidad De Investigacion Clinica en Medicina

Monterrey, Nuevo Leon, Nuevo León, Mexico

Countries

Argentina; Brazil; Chile; Mexico

References

Oudiz RJ, Galie N, Olschewski H, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Harrison BC, Despain D, Dufton C, Rubin LJ; ARIES Study Group. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Nov 17;54(21):1971-81. doi: 10.1016/j.jacc.2009.07.033.

Reference Type: DERIVED

PMID: 19909879 (View on PubMed)

Other Identifiers

ARIES-E

Identifier Type: -

Identifier Source: secondary_id

AMB-320/321-E

Identifier Type: -

Identifier Source: org_study_id