ARIES - Ambrisentan in Patients With Moderate to Severe Pulmonary Arterial Hypertension (PAH)

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

Detailed Description
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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.

Official Title
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ARIES 1 and ARIES 2: Ambrisentan in PAH - A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, Efficacy Study of Ambrisentan in Subjects With Pulmonary Arterial Hypertension

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Ambrisentan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ambrisentan|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline at Week 12 of six minute walk distance |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline at Week 12 of: |  |  | 
| Borg Dsypnea Index |  |  | 
| WHO Functional Classification |  |  | 
| SF-36 |  |  | 
| Time to Clinical Worsening |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Arterial Hypertension