Safety
cirrhosis, TEAEs, Decreases in systolic and diastolic BP, hypotension, orthostatic intolerance
CIRRHOSIS
In this Phase Ib trial, BI 685509 was generally well tolerated, with 2 AEs leading to treatment discontinuation and 3 serious AEs, restricted to patients with CP-B cirrhosis and assessed as not drug-related. The frequency of TEAEs and drug-related AEs was higher in patients with CP-B cirrhosis (32.0% and 20.0%, respectively) compared with patients with CP-A cirrhosis (12.5% and 8.3%, respectively), with orthostatic intolerance being the most frequently reported drug-related AE (n = 1 each per CP-A 3 mg BID, CP-B 2 mg BID, and CP-B 3 mg BID). Decreases in systolic and diastolic BP and an increase in HR were seen in patients receiving BI 685509 compared with placebo; however, no dose relationship was observed in either patient group. This could be a benefit of the mechanism of action of this therapy compared with NSBBs, with which hypotension often occurs in patients with CP-B cirrhosis.