The primary objective is to determine the effect of ambrisentan on exercise capacity in subjects with PAH.

Condition	Treatment or Intervention	Phase
Pulmonary Hypertension	Drug: Ambrisentan	Phase III

ARIES-1 in North America and Australia

ARIES-2 in Western and Eastern Europe, South America and Israel

Subjects in these randomized studies will receive one of two doses of ambrisentan or placebo. Inclusion is not based on a specified WHO functional classification. Rather, subjects with WHO Class I-IV symptoms are eligible if their 6-minute walk distance is 150-450 meters and they meet the study-specified hemodynamic criteria. Subjects with anorexigen or HIV infection related PAH are eligible but subjects with congenital heart disease and pediatric subjects are excluded. The study requires a historical cardiac catheterization and other diagnostic procedures.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Diagnosis of idiopathic PAH (formally known as PPH), or PAH associated with collagen vascular disease, anorexigen use, or HIV infection;
• Historical cardiac catheterization with the following hemodynamic criteria: Mean pulmonary artery pressure greater than or equal to 25 mmHg; Pulmonary vascular resistance greater than 3 mmHg/L/min; Pulmonary capillary wedge pressure or left ventricular end diastolic pressure less than 15 mmHg;
• 6-minute walk distance of at least 150 meters, but no more than 450 meters;
• Total lung capacity greater than or equal to 70% and FEV1 greater than or equal to 65% of predicted normal;

Exclusion Criteria:

• Portopulmonary hypertension;
• Subjects with PAH due to or associated with coronary artery disease, left heart disease, interstitial lung disease, chronic obstructive pulmonary disease, veno-occlusive disease, chronic thromboembolic disease, or sleep apnea;
• Bosentan (Tracleer®), sildenafil (Viagra®), or chronic prostanoid therapy within 4 weeks of screening;
• Serum ALT or AST lab value that is greater than 1.5 times the upper limit of normal;
• Contraindication to treatment with an endothelin receptor antagonist;
• Subject with cardiovascular, hepatic, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that may adversely affect the safety of the subject;
• Participation in a clinical study involving another investigational drug within 4 weeks of screening.

ARIES PAH Hotline      1-877-ARIESPH (877-274-3774) 

Arizona
      Pulmonary Associates, PA, Phoenix,  Arizona,  85006,  United States; Recruiting
California
      University of California-Davis, Sacramento,  California,  95817,  United States; Recruiting
      Los Angeles County Harbor-UCLA Medical Center, Torrance,  California,  90502,  United States; Recruiting
      University of California San Diego Medical Center, San Diego,  California,  92037,  United States; Recruiting
      University of Southern California, Los Angeles,  California,  90089,  United States; Recruiting
Colorado
      Myogen, Westminster,  Colorado,  80021,  United States; Recruiting
      University of Colorado Health Sciences Center, Denver,  Colorado,  80262,  United States; Recruiting
Connecticut
      University of Connecticut Health Center, Farmington,  Connecticut,  06030,  United States; Recruiting
Florida
      Mt. Sinai Medical Center, Miami,  Florida,  33140,  United States; Recruiting
Georgia
      Medical College of Georgia, Augusta,  Georgia,  30912,  United States; Recruiting
      Emory University Hospital, Atlanta,  Georgia,  30322,  United States; Recruiting
Illinois
      Loyola University Medical Center, Chicago,  Illinois,  60153,  United States; Recruiting
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States; Recruiting
Louisiana
      Ochsner Clinic, New Orleans,  Louisiana,  70121,  United States; Recruiting
Maine
      Maine Medical Center, Portland,  Maine,  04102,  United States; Recruiting
Massachusetts
      Brigham and Women's Hospital, Boston,  Massachusetts,  02115,  United States; Recruiting
      Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States; Recruiting
Michigan
      University of Michigan Medical Center, Ann Arbor,  Michigan,  48109,  United States; Not yet recruiting
      Wayne State University, Detroit,  Michigan,  48201,  United States; Recruiting
Minnesota
      Mayo Clinic, Rochester,  Minnesota,  55905,  United States; Recruiting
Missouri
      Washington University, St. Louis,  Missouri,  63110,  United States; Not yet recruiting
New York
      New York Presbyterian Hospital, New York,  New York,  10032,  United States; Recruiting
      Cardiology PC, Syracuse,  New York,  13210,  United States; Not yet recruiting
      Winthrop University Hospital, Mineola,  New York,  11501,  United States; Not yet recruiting
      Mt. Sinai Medical Center, New York City,  New York,  10029,  United States; Recruiting
      Northshore University/Long Island Jewish Hospital, Manhasset,  New York,  11030,  United States; Recruiting
Ohio
      University Hospitals of Cleveland, Cleveland,  Ohio,  44106,  United States; Recruiting
      Lindner Clinical Trial Center, Cincinnati,  Ohio,  45219,  United States; Recruiting
      Cleveland Clinic Foundation, Cleveland,  Ohio,  44195,  United States; Recruiting
Oregon
      Oregon Health Sciences University, Portland,  Oregon,  97202,  United States; Recruiting
Pennsylvania
      University of Pittsburgh Medical Center, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
      University of Pennsylvania Hospital, Philadelphia,  Pennsylvania,  19104,  United States; Not yet recruiting
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States; Recruiting
Tennessee
      Vanderbilt University Medical Center, Nashville,  Tennessee,  37232,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
      St. Paul Hospital, Dallas,  Texas,  75235,  United States; Recruiting
Virginia
      Virginia Commonwealth University, Richmond,  Virginia,  23298,  United States; Recruiting
      University of Virginia Health System, Charlottesville,  Virginia,  22908,  United States; Recruiting
Wisconsin
      Heart Care Associates, Milwaukee,  Wisconsin,  53215,  United States; Recruiting
Canada, Quebec
      Jewish General Hospital, Montreal,  Quebec,  H3T1E2,  Canada; Recruiting

Study chairs or principal investigators

Lewis J. Rubin, MD,  Study Chair,  University of California San Diego, San Diego School of Medicine   

Study ID Numbers:  ARIES
Record last reviewed:  October 2004
Record first received:  September 10, 2004
ClinicalTrials.gov Identifier:  NCT00091598
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-09