End points
liver stiffness, treatment-emergent adverse, cirrhosis, NAFLD fibrosis
DISEASE, CIRRHOSIS, LIVER FIBROSIS, CHRONIC LIVER DISEASE
The primary end point was the number of patients with drug-related AEs across different dose regimens over each dose escalation. Secondary safety end points were assessed after 28 days of treatment as the change from baseline in seated systolic BP, seated diastolic BP, HR, and bodyweight. Further safety end points were assessed based on treatment-emergent adverse events (TEAEs), safety laboratory parameters, vital signs, and 12-lead ECG.Secondary PK end points were AUC from time 0 to the last quantifiable data point (AUCExploratory efficacy end points in patients with CP-A and CP-B cirrhosis were the change from baseline in liver stiffness measured by FibroScan (any available model; Echosens) on days 16 and 27, and in patients with CP-A cirrhosis only, the change from baseline in spleen stiffness measured by FibroScan (Expert 630 Professional; Echosens) on days 16, 17, 27, and 28, and the change from baseline in liver function measured by the disease severity index, d4-cholate at 60 minutes (HepQuant STAT), and SHUNT using the HepQuant SHUNT test (HepQuant) on days 11 and 27. Additional exploratory end points included total serum levels of cytokeratin 18 (M65), caspase-cleaved cytokeratin 18 (M30), Pro-C3, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase, bilirubin and C-reactive protein, and composite scores (enhanced liver fibrosis test, NAFLD fibrosis, fibrosis-4, aspartate aminotransferase-to-platelet ratio index, and MELD. The changes from baseline after 27 days of treatment in patient-reported outcomes (EQ-5D-5L and chronic liver disease questionnaires) were defined as other end points.