A Study to Compare the Macitentan-tadalafil Fixed Dose Combination Tablet Relative to the Concomitant Administration of the Reference Tablets of Macitentan and Tadalafil in Healthy Subjects

Key Inclusion Criteria:

• Signed informed consent
• Male and female subjects aged between 18 and 55 years (inclusive) at screening
• Healthy on the basis of the physical examination, vital signs, 12-lead ECG, and laboratory tests performed at screening
• Women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day-1 or must be of non-childbearing potential.
• Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at screening
• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 bpm (inclusive)

Key Exclusion Criteria:

• Known hypersensitivity to any active substance or drugs of the same class, or any excipients of the drug formulation(s)
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study treatment(s)
• Values of hepatic aminotransferase (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) > 3 X upper limit of normal at screening
• Loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy
• Known hereditary degenerative retinal disorders, including retinitis pigmentosa
• Priapism and anatomical deformation of the penis
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
• Treatment with another investigational drug within 3 months prior to screening or participation in more than 4 investigational drug studies within 1 year prior to screening
• Excessive caffeine consumption, defined as > or = 800 mg per day at screening.
• Nicotine intake (e.g., smoking, nicotine patch, nicotine chewing gum, or electronic cigarettes) within 3 months prior to screening and inability to refrain from nicotine intake from screening until end-of-study (EOS; washout period included)
• Previous treatment with any prescribed medications (including vaccines) or over the counter (OTC) medications within 3 weeks prior to first study treatment administration.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.