Procedures
orthostatic, Spleen stiffness, cirrhosis, Liver stiffness
ADVERSE EVENT, LIVER, CIRRHOSIS
Treatment was administered to patients on site after an overnight fast on days 1, 4–5, 10–11, 16–17, and 27–28. Treatment administered at home (days 6–9, 12–15, and 17–26) was taken with a glass of water immediately before or during breakfast (and dinner if BID) at approximately the same time each day; for BID dosing, there was an interval of ≥ 10 hours between doses. On days 5, 11, and 17, the morning dose was administered on site, and the second dose was administered at home.Assessments of PK, vital signs, BP, heart rate (HR), 12-lead ECG, orthostatic tests, safety laboratory tests, and CP status were carried out on site (days 1, 4, 10, 16, 28, and 31 for all; PK was assessed on days 2 and 3; PK and vital signs were assessed on days 27–31 inclusive). Liver stiffness (transient elastography) and fat content (controlled attenuation parameter) were assessed by FibroScan (any available model; Echosens, Paris, France) in a fasted state on days 1, 16, and 27. Spleen stiffness (transient elastography) was assessed by FibroScan Expert 630 Professional (Echosens) in compensated patients with CP-A cirrhosis on days 1, 16, 17, 27, and 28, also in a fasted state. Liver function was assessed by the HepQuant SHUNT test (HepQuant, Denver, CO, USA) in patients with CP-A cirrhosis at screening and on days 11 and 27, with 6 blood samples (each 3 mL) taken per test (ie, predose, and at 5, 20, 45, 60, and 90 min postdose). Adverse events (AEs) were assessed daily.Treatment was administered to HVs on site after an overnight fast on day 1. PK were assessed on days 1–4; vital signs were assessed on days 1, 2, and 4; 12-lead ECG, physical examinations, and orthostatic tests were assessed on days 1 and 4; and AEs were assessed daily from screening to the end of observation (day 8).