A Open Label Study to Assess the Long-term Safety, Tolerability and Efficacy of Ambrisentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Condition: Hypertension
MeSH terms: Hypertension, Pulmonary; Hypertension
Intervention: Ambrisentan 5 mg
Intervention description: Round, white, film-coated, immediate-release tablets, containing 5 mg ambrisentan. Subjects will be dosed orally once daily. Subjects may receive 5mg, or 10 mg of ambrisentan OD.
Intervention MeSH terms: Ambrisentan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Inoperable chronic thromboembolic pulmonary hypertension, endothelin receptor antagonist

Summary:

      This is an open label, long term extension to Study AMB115811. All subjects may remain in the
      extension study for a minimum of 18 months. Beyond the 18-month period, subjects may continue
      in the extension study until one of the following: the product is approved locally for use in
      inoperable CTEPH patients; development for use in the CTEPH population is discontinued or
      product is not approved by the local regulatory authorities; or the investigator decides to
      discontinue the subject or subject decides to discontinue from the study. The primary purpose
      of this study is to provide clinically relevant information on the long term safety of
      ambrisentan in subjects with inoperable CTEPH.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have been randomized to the protocol for AMB115811 and have met one of the following:
             Completed the Week 16 visit in AMB115811; Or Prematurely withdrew from AMB115811 for
             whatever reason (where investigational product [IP] has been stopped due to safety or
             efficacy reasons, the subject may still enter into the open label study regardless of
             what treatment they are receiving [other treatments will not be supplied by the
             sponsor]. The investigator will decide whether or not the subject will receive the IP

          -  Subject is able and willing to give written informed consent. As part of the consent,
             female subjects of childbearing potential will be informed of the risk of
             teratogenicity and will need to be counseled in a developmentally appropriate manner
             on the importance of pregnancy prevention; and male subjects will need to be informed
             of potential risk of testicular tubular atrophy and aspermia.

          -  Specific information regarding warnings, precautions, contraindications, adverse
             events, and other pertinent information on the GSK investigational product or other
             study treatment that may impact subject eligibility is provided in the Investigators
             Brochure and product label for PAH indication.

          -  In France, a subject will be eligible for inclusion in this study only if either
             affiliated to or a beneficiary of a social security category

        Exclusion Criteria:

          -  Subject meeting any of the following criteria must not receive ambrisentan, however
             may still be followed-up as part of the study and be treated according to best
             clinical practice as decided by the investigator:

          -  Subject has a known hypersensitivity to the Investigational Products, the metabolites,
             or formulation excipients

          -  Female subjects who are pregnant or breastfeeding or no-longer agree to comply with
             using effective contraception as defined in the protocol.

          -  Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
             >= 3x Upper limit of normal (ULN)

          -  Subjects with bilirubin >= 2xULN (>35% direct bilirubin)

          -  Subjects with severe renal impairment (estimated creatinine clearance <30 millilitre
             per minute (mL/min) assessed within the previous 45 days) at the point of transition
             from Study AMB115811

          -  Subject has moderate - severe hepatic impairment (Child-Pugh class B-C with or without
             cirrhosis) at the point of transition from study AMB115811

          -  Subject with clinically significant fluid retention in the opinion of the investigator

          -  Subject with clinically significant anemia in the opinion of the investigator

          -  Subjects who are to enter another clinical trial or be treated with another
             investigational product after exiting Study AMB115811.