Clinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension

Inclusion Criteria:

- Written informed consent

- Subject with CTEPH (WHO Group 4) judged as inoperable due to the localization of the
obstruction being surgically inaccessible (i.e., distal disease).

- Female of childbearing potential must have a negative pre-treatment serum pregnancy
test, be advised on appropriate methods of contraception, and agree to use 2 reliable
methods of contraception.

Exclusion Criteria:

- Previous pulmonary endarterectomy.

- Recurrent thromboembolism despite sufficient oral anticoagulants.

- Symptomatic acute pulmonary embolism in the 6-month period prior to randomization.

- Known moderate-to-severe restrictive lung disease (i.e., TLC < 60% of predicted
value) or obstructive lung disease (i.e., FEV1 < 70% of predicted, with FEV1/FVC <
65%) or known significant chronic lung disease diagnosed by chest imaging (e.g.,
interstitial lung disease, emphysema).

- Acute or chronic conditions (other than dyspnea) that limit the ability to comply
with study requirements in the 3-month period prior to Screening visit or during the
Screening period.