Ambrisentan for Inoperable Chronic Thromboembolic Pulmonary Hypertension.

Inclusion Criteria:

- Signed written informed consent prior to beginning study-related procedures.

- Subject must be between 18-80 years of age, inclusive, at the Screening Visit.

- Subjects must have a diagnosis of CTEPH at an expert centre with a positive V/Q and
CT angiogram and a pulmonary angiogram if available within 6 months prior to
screening.

- Subject must meet all of the following haemodynamic criteria by means of a RHC within
3 months prior to screening: Mean pulmonary artery pressure (mPAP) of >25 millimeters
of mercury (mmHg), Pulmonary vascular resistance (PVR) >400 dynes.sec/centimetre
(cm)^5, Pulmonary capillary wedge pressure (PCWP) or Left ventricle end diastolic
pressure (LVEDP) of <15 mmHg.

- Subjects must have previously been judged inoperable due to the obstruction being
surgically inaccessible (i.e. distal disease) by an expert multidisciplinary team
which must include at least one cardiology or respiratory consultant, and one
consultant PEA surgeon. For countries with CTEPH expert centers [including at least a
surgeon with sound experience performing Pulmonary Endarterectomy (PEAs)] the expert
team will be the local expert centre. For countries without a CTEPH surgical expert
center a central adjudication committee will assess the operability of the subjects
during the screening period.

- Subject must walk a distance of >150 Meters (m) and < 475 m at the screening visit.

- Subject must have a current diagnosis of being in WHO Functional Class II or III.

- Subject, with or without supplemental oxygen, must have a resting arterial oxygen
saturation (SaO2) > 92% as measured by pulse oximetry at the Screening Visit.

- Subjects must have received anticoagulation for a minimum of 3 months prior to
Screening

- Female subject of childbearing potential must agree to use 2 reliable methods of
contraception from the Screening Visit until study completion and for at least 30
days following the last dose of Investigational Product

- Subject must agree not to participate in a clinical study involving another
investigational drug or device throughout this study.

- Subject must be competent to understand the information given in the Institutional
Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent
form (ICF) and must sign the form prior to the initiation of any study procedures.

Exclusion Criteria:

- Subject received previous Pulmonary arterial hypertension (PAH) therapy
(Phosphodiesterase type 5 [PDE5i], Endothelin receptor antagonist [ERA], chronic
prostanoid use)

- Subject has previously discontinued other ERA in either another clinical study or
commercial product for safety or tolerability reasons other than for liver function
abnormalities.

- Subject has a known hypersensitivity to the Investigational Products, the
metabolites, or formulation excipients

- Subject has previously undergone a pulmonary endarterectomy or a balloon pulmonary
angioplasty

- Subject receiving intravenous inotropes within 2 weeks prior to the Screening Visit
(e.g. dopamine, dobutamine)

- Subjects receiving Calcium Channel Blockers or 5-hydroxy-3-methylglutaryl-coenzyme A
5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins)
on an unstable dose 4 weeks prior to the Screening Visit (to be eligible subjects
must not have changed their dose <4 weeks prior to the screening visit)

- Subject has not enrolled in an exercise training program for cardiopulmonary
rehabilitation within 12 weeks prior to the Screening Visit and must agree not to
enroll in an exercise training program for pulmonary rehabilitation during the
Screening Period and the first 16 weeks of the study. Subjects enrolled in an
exercise program for pulmonary rehabilitation 12 weeks prior to screening may enter
the study if they agree to maintain their current level of rehabilitation for the
first 16 weeks of the study.

- Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) > 3x Upper
limit of normal (ULN)

- Bilirubin > 1.5xULN (>35% direct bilirubin)

- Subject has severe renal impairment [estimated creatinine clearance <30
millilitre/minute (mL/min)] at the Screening Visit

- Subject has moderate - severe hepatic impairment (Child-Pugh class B-C with or
without cirrhosis) at the Screening Visit

- Subject has clinically significant anaemia: Hemoglobin (Hb) < 10 grams/decilitre
(g/dL)

- Subjects with bleeding disorders or significant active peptic ulceration in the
opinion of the investigator

- Subject has uncontrolled hypertension (>180/110 mmHg) at screening

- Subject has severe hypotension (<90/50 mmHg) at screening

- Subject has had an acute myocardial infarction within the last 90 days prior to
screening

- Subject has, in the opinion of the investigator, clinically significant aortic or
mitral valve disease; pericardial constriction; restrictive or congestive
cardiomyopathy; life-threatening cardiac arrhythmias; significant left ventricular
dysfunction (ejection fraction <50% of normal); left ventricular outflow obstruction;
symptomatic coronary artery disease; autonomic hypotension; fluid depletion.

- Subject with significant pulmonary disease Forced expiratory volume in 1 second
(FEV1) <70% of predicted): Chronic obstructive pulmonary disease (COPD), Emphysema,
evidence of fibrotic lung disease on imaging

- Subject has clinically significant fluid retention in the opinion of the investigator

- Subject with significant obesity [Body mass index (BMI) ≥35], cardiovascular,
musculoskeletal or any other condition that in the opinion of the investigator may
involve an impairment of exercise capacity or the performance of the 6MWD test (e.g.
previous history of hip/knee surgery, lower limb ulcers associated with autoimmune
diseases)

- Subject with cardiovascular, liver, renal, haematologic, 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 investigational product or severely limit the lifespan of the subject
other than the condition being studied

- Subjects with a prior malignancy whose cancer is expected to require additional
active treatment in the next 2 years and whose prior malignancy would prevent them
from fully participating in the study

- Female subject who is pregnant or breastfeeding

- Subject has demonstrated noncompliance with previous medical regimens

- Subject has a recent (within 1 year) history of abusing alcohol or illicit drugs

- Subject has participated in a clinical study involving another investigational drug
or device within 4 weeks before the Screening Visit.