|Exclusion Criteria:||1) Histology other than astrocytoma grade IV (GBM or gliosarcoma)|
2) Tumor foci detected below the tentorium or beyond the cranial vault.
3) Glioblastoma or gliosarcoma disease with leptomeningeal spread.
4) Patients with a history of any other cancer, unless in complete remission, and off all therapy for that disease for a minimum of 5 years (except history of basal or squamous cell skin cancers that are completely excised/cured at time of enrollment).
5) Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin greater than the upper limit of normal (ULN).
6) Moderate to severe hepatic impairment, i.e., Child-Pugh Class B/C.
7) Positive results from Human immunodeficiency virus (HIV) serology testing, if any available.
8) Supine systolic blood pressure < 100 mmHg or supine diastolic blood pressure < 50 mmHg at screening (Visit 1) and baseline (Visit 2), or documented medical history of orthostatic hypotension.
9) Renal insufficiency (estimated creatinine clearance < 50 mL/min, or serum creatinine exceeding laboratory ULN at screening).
10) Females who are pregnant or lactating or plan to become pregnant during the course of this study.
11) Substance or alcohol abuse or dependence, within 12 months prior to screening (Visit 1).
12) Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to screening (Visit 1).
13) Treatment with cytochrome P450 3A4 (CYP3A4) inducers, such as rifabutin, rifampin, rifapentin, carbamazepine and derivates, phenobarbital, phenytoin, St. John's wort within 3 weeks prior to screening (Visit 1)
14) Treatment with strong CYP3A4 inhibitors such as ketoconazole, itroconazole, nefazodone, chloramphenicol, clarithromycin, telithromycin, ritonavir, indinavir, nelfinvar, and saquinavir within 2 weeks prior to screening (Visit 1).
15) Known hypersensitivity to endothelin receptor antagonists, or any of the excipients of macitentan tablets.
16) Prior chemotherapy for recurrent GBM with nitrosourea compounds including GliadelŪ (carmustine) wafers or bevacizumab.
17) Prior focal radiotherapy (stereotactic radiotherapy or Gamma Knife).
18) Planned treatment, or treatment with any investigational drug within 4 weeks prior to screening (Visit 1).
19) Severe, active co-morbidity, including: Cardiac disease - congestive heart failure class III/IV New York Heart Association (NYHA); unstable angina or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening; chronic hepatitis B or C infection; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening; hematological and bone marrow diseases. Severe malabsorption (defined as > 15% unintentional loss of body weight in the last 6 months prior to study enrollment).
20) Any condition that prevents compliance with the protocol or adherence to therapy.