Effect of BIA 5-1058 400 mg on the Steady State Pharmacokinetics of Bosentan

Exclusion criteria

• ✕. Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue disease or disorders within 5 years before the first IMP administration.
• ✕. Documented coronary artery disease (any of prior myocardial infarction, positive stress test, positive nuclear perfusion study, prior coronary artery bypass graft \[CABG\] surgery or percutaneous coronary intervention, angiogram showing at least 75% stenosis in a major coronary artery), acute coronary syndrome or current symptoms of myocardial ischemia and angina.
• ✕. Clinically relevant surgical history involving the stomach and/or intestinal system, potentially affecting absorption of IMPs.
• ✕. Any clinically relevant findings in the laboratory tests, particularly any abnormality in the coagulation tests or the liver function tests, as judged by the Principal Investigator, at the Screening Visit and on admission to each treatment period. If a laboratory assessment was outside of the reference range at the local laboratory at the Screening Visit or baseline, the assessment could have been repeated once as soon as possible and in any cases before enrollment to rule out laboratory error.
• ✕. Subjects with alanine aminotransferase (ALT) \> 1.0 x the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) \> 1.0 x ULN and/or total bilirubin \> 1.0 x ULN (isolated bilirubin \> 1.0 x ULN and 1.5 x ULN was acceptable if bilirubin was fractionated and direct bilirubin \< 35%), as confirmed by subsequent repeat assessment, at the Screening Visit and on admission to each treatment period.
• ✕. History of relevant atopy or drug hypersensitivity.
• ✕. History of alcoholism or drug abuse.
• ✕. History of drinking \> 24 g (males) and \> 12 g (females) of pure alcohol per day (10 g pure alcohol = 250 mL of beer \[5%\] or 35 mL of spirits \[35%\] or 100 mL of wine \[12%\]) within 3 months before first admission to the clinical unit.