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

NCT00578786 | Completed Phase 3 Results DMC

• 2 other identifiers: AMB-320/321-EARIES-E
• Study Type: interventional
• Target: 383
• Locations: 4 countries
• Sites: 22

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (2)

• Frequently Reported (15% or More Overall) Adverse Events by Severity

  The primary endpoint of this study is the incidence and severity of adverse events associated with long-term exposure to AMB in participants with PAH. The most frequently occurring adverse events (occurring in 15% or more of the participants in the combined group) are presented, by severity, that began after entering this extension study. Adverse events that were serious are included. Adverse events are coded according to the Medical Dictionary for Regulatory Activities (MedDRA) Version 6.1 and are presented by MedDRA preferred term. Severity was graded as follows: mild (AE did not interfere with routine activities; subject may have experienced slight discomfort), moderate (AE interfered with routine activities; subject may have experienced significant discomfort), and severe (AE made it impossible to perform routine activities; subject may have experienced intolerable discomfort or pain).

  Baseline to Week 295

• Serum Aminotransferases Relative to the Upper Limit of the Normal Range (ULN)

  The number of participants with serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) falling into the following categories: \>3.0 and \</= 5.0 x ULN, \>5.0 and \</= 8.0 x ULN, and \>8.0 x ULN. Includes the highest value per participant across all visits as well as values from early termination visits.

  Baseline to Week 295

Secondary Outcomes (20)

• Baseline Exercise Capacity as Measured by the 6-Minute Walk Distance Test

  Baseline

• Change From Baseline to Week 24 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test

  Baseline to Week 24

• Change From Baseline to Week 48 (Year 1) in Exercise Capacity as Measured by the 6-Minute Walk Distance Test

  Baseline to Week 48

• Change From Baseline to Year 2 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test

  Baseline to Year 2

• Change From Baseline to Year 3 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test

  Baseline to Year 3

Study Arms (1)

Ambrisentan

EXPERIMENTAL

2.5, 5 or 10 mg ambrisentan

Drug: ambrisentan

Interventions

ambrisentan DRUG

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

Also known as: Letairis(TM)

Ambrisentan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• Subject receiving bosentan, sildenafil, or iv inotropes at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit;
• 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;
• Female subject who is pregnant or breastfeeding;
• 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;
• Subject who has demonstrated noncompliance with previous medical regimens;
• Subject who has a recent history of abusing alcohol or illicit drugs;
• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (22)

Sanatorio Otamendi

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1115AAB, Argentina

Location

Hospital Britanico-Buenos Aires

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1280AEB, Argentina

Location

Instituto del Corazon Denton A. Cooley

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1416A, Argentina

Location

UAI Hosp. Universitario

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1437BZL, Argentina

Location

HIGA Hospital Interzonal General de Agudos Oscar Allende

Mar del Plata, Buenos Aires, 07600, Argentina

Location

Clinica Independencia Munro

Munro, Buenos Aires, 01605, Argentina

Location

Instituto de Cardiologia J.F. Cabral

Corrientes, Corrientes Province, W3400AMZ, Argentina

Location

Sanatorio Allende

Córdoba, Córdoba Province, X5000JHQ, Argentina

Location

Hospital Italiano de Cordoba

Córdoba, Córdoba Province, X5004 FJE, Argentina

Location

Hospital Italiano de Rosario

Rosario, Sante Fe, 02000, Argentina

Location

Hospital Privado Centro Medico de Cordoba

Córdoba, X5016KEH, Argentina

Location

Hospital Universitario Clementino Fraga Filho

Ilha Do Fundao, Rio de Janeiro, 21941-590, Brazil

Location

Hospital Madre Teresa

Belo Horizonte, 30380-090, Brazil

Location

Hospital San Lucas de Pontificia Universidade Catolica

Porto Alegre, 90610-000, Brazil

Location

Complexo Hospitalar Sanata Casa de Porto Alegre

Porto Alegre, 92020-090, Brazil

Location

Universidade do Estado de Sao Paulo - UNIFESP

São Paulo, 04023-062, Brazil

Location

Hospital das Clinicas da FMUSP

São Paulo, 05403-000, Brazil

Location

Hospital San Juan de Dios

Santiago, Santiago de Chile, CP 8330024, Chile

Location

Hospital Clinico Universidad Catolica

Santiago, Santiago de Chile, CP 8350488, Chile

Location

Instituto Nacional del Torax

Santiago, Santiago de Chile, CP7500691, Chile

Location

Instituto Nacional de Cardiologia Ignacio Chavez

Mexico City, Mexico City, 14080, Mexico

Location

Unidad De Investigacion Clinica en Medicina

Monterrey, Nuevo Leon, Nuevo León, 64718, Mexico

Location

Related Publications (1)

• 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.

  PMID: 19909879 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Analysis included those not enrolling in this study but received AMB in 1 of the 2 parent studies. At Year 3, almost half of those randomized to 2.5 mg were titrated to 5 mg and 10 mg; a third starting at 5 mg were titrated to 10 mg.

Results Point of Contact

• Title: Hunter Gillies, MD, DSEM
• Organization: Gilead Sciences, Inc.

hunter.gillies@gilead.com

650-522-1214

Study Officials

• Chris Dufton, PhD

  Gilead Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: February 1, 2004
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: January 15, 2013
• Results First Posted: January 15, 2013

Record last verified: 2013-01

Locations

BR (6); CL (3); AR (11); ME (2)