Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
Condition: Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Hypertension
Intervention: Ambrisentan
Intervention description: Oral tablets taken once daily.
Intervention MeSH terms: Ambrisentan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 224.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in
      a broad population of participants with pulmonary hypertension (PH). Secondary objectives of
      this study were to evaluate the effects of ambrisentan on other clinical measures of
      pulmonary arterial hypertension (PAH), long-term treatment success, and survival.
    

Eligibility criteria:

        Summarized Inclusion Criteria:

          1. 18 years of age or older

          2. Current diagnosis of PH associated with an acceptable etiology as outlined in the
             protocol, including: PH due to the following etiologies: 1) PAH including idiopathic
             and familial PAH and PAH associated with collagen vascular disease, congenital
             systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human
             immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen
             storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1);
             2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive
             pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing,
             and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal
             chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO
             Group 5).

          3. Stable regimen (within four weeks) of chronic prostanoid, PDE-5 inhibitor, calcium
             channel blocker, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
             inhibitor therapy

          4. Right heart catheterization completed prior to screening must meet pre-specified
             criteria

          5. Female participants of childbearing potential must have a negative serum pregnancy
             test and must agree to use a reliable double method of contraception until study
             completion and for at least four weeks following their final study visit.

          6. Male participants must be informed of the potential risks of testicular tubular
             atrophy and infertility associated with taking ambrisentan and queried regarding his
             understanding of the potential risks as described in the Informed Consent Form.

        Summarized Exclusion Criteria:

          1. Participation in a previous clinical study with ambrisentan

          2. Bosentan or sitaxsentan use within four weeks prior to the screening visit

          3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is
             greater than 3 times the upper limit of normal at the screening visit

          4. Pulmonary function tests not meeting the following pre-specified criteria: 1) mean
             pulmonary arterial pressure (PAP) >= 25 mm Hg; 2) PVR > 3 mm Hg/L/min; 3) pulmonary
             capillary wedge pressure (PCWP) or left ventricle end diastolic pressure (LVEDP) < 15
             mm Hg; 4) total lung capacity (TLC) >= 70% of predicted normal for participants
             without ILD or >= 60% of predicted normal in participants with ILD; forced expiratory
             volume in 1 second (FEV1) >= 65% of predicted normal in participants without COPD or
             >= 50% of predicted normal in participants with COPD

          5. Contraindication to treatment with endothelin receptor antagonist (ERA)

          6. History of malignancies other than basal cell carcinoma of the skin or in situ
             carcinoma of the cervix within the past five years

          7. Female participant who is pregnant or breastfeeding