Table 2.
Main exclusion criteria applicable to both studies
| Exclusion criteria applicable to all individuals |
|---|
| History of medical disorders or conditions that could impair an individual’s ability to participate in or complete the study |
| Febrile illness in the week before the study |
| History of severe allergies and nonallergic drug reactions |
| Pathological changes in the electrocardiogram, such as a second- or third-degree atrioventricular block, prolongation of the QRS complex to more than 120 ms, or prolongation of the QT/QTc interval to more than 450 ms |
| Participation in another clinical study in the previous 3 months |
| Donation of more than 100 mL of blood in the preceding 4 weeks or 500 mL in the preceding 3 months |
| Pregnant women and women of childbearing age not using double-barrier contraception |
| Exclusion criteria applicable to patients with liver cirrhosis and hepatic impairment |
| Concurrent diagnosis of severe cerebrovascular or cardiac disorders, renal failure with a CLCR of 40 mL/min or lower (according to the Cockcroft-Gault formula),22 grade III or IV hepatic encephalopathy, or failure of any organ system other than the liver |
| Primary and secondary biliary cirrhosis |
| Sclerosing cholangitis |
| Diagnosis of malignancy within the previous 5 years |
| Severe infection or any clinically significant illness in the 4 weeks before drug administration |
| Percutaneous transluminal coronary angioplasty or coronary artery bypass graft less than 6 months before riociguat administration |
| Concomitant thrombotic disorders |
| Platelet count less than 50 × 109/L |
| Diabetes mellitus with a fasting blood glucose level higher than 220 mg/dL or glycosylated hemoglobin levels of more than 10% |
| History of bleeding in the past 3 months |
| Ascites of more than 6 L (estimated by ultrasound) |
| Prothrombin time (Quick test) below 40% |
| Alkaline phosphatase level at least three times the ULN |
| Elevated AST or ALT in conjunction with a GGT level at least three times the ULN (an isolated elevation of GGT ≥3 times the ULN did not result in exclusion from the study) |
| Cholinesterase lower than 1,800 U/L |
| Total bilirubin higher than 102 μmol/L |
| Concomitant use of potent CYP3A4 inhibitors, phosphodiesterase 5 inhibitors, endothelin receptor antagonists, or prostacyclins or treatment with any medication (except those necessary for the treatment of liver disease or related complications) |
| Change in chronic medication less than 4 weeks before dosing |
Note
ALT: alanine aminotransferase; AST: aspartate aminotransferase; CLCR: creatinine clearance; GGT: glutamyl transpeptidase; ULN: upper limit of normal.