A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202)
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: ambrisentan
Intervention description: 2.5, 5.0 or 10.0 mg ambrisentan po, qd, long-term
Intervention MeSH terms: Ambrisentan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 383.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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:

          -  Subjects must have met the exclusion criteria of the AMB-320 (NCT00423748) and AMB-321
             (NCT00423202)studies. In addition, a subject who meets any one of the following
             criteria is ineligible for participation in the study:

               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.