Study participants and compliance
delirium, ascites, cirrhosis, encephalopathy, hematemesis, liver stiffness, variceal bleeding
AUTOIMMUNE HEPATITIS, ASCITES, HEMOCHROMATOSIS, EVENTS, CIRRHOSIS, GASTROINTESTINAL BLEEDING, LIVER DISEASE, ENCEPHALOPATHY, ADVERSE EVENT, ALD, DISEASE CHARACTERISTIC
In total, 96 participants were screened (CP-A, n = 41; CP-B, n = 35; HVs, n = 20; March 8, 2019, to February 3, 2021); of these, 24 patients with CP-A cirrhosis (n = 6 each per dose group and placebo), 25 patients with CP-B cirrhosis (n = 6 each per 1 mg BID and 2 mg BID; n = 7, 3 mg BID; n = 6, placebo), and 15 HVs (n = 12, BI 685509 0.5 mg once daily; n = 3, placebo) were treated (Figure Participant disposition. (A) Child–Pugh class A and B patients; (B) healthy volunteers. *One CP-B patient in the 2 mg BID group was removed from the trial due to a serious AE of delirium. Abbreviations: AE, adverse event; BID, twice daily; CP, Child–Pugh.Patient demographics, disease characteristics, and biomarkersOther etiologies: CP-A 3 mg BID, hemochromatosis; CP-B 2 mg BID, autoimmune hepatitis.Abbreviations: ALD, alcohol-associated liver disease; BID, twice daily; CP, Child–Pugh; LSM, liver stiffness measurement; QD, once daily.In patients with CP-A cirrhosis, prior decompensating events were ascites (n = 1, placebo), encephalopathy (n = 2, 1 mg BID; n = 1, placebo), variceal bleeding (n = 1 each per 3 mg BID and placebo), gastrointestinal bleeding (n=1, 3 mg BID), and elevated bilirubin (n = 1, placebo). In patients with CP-B cirrhosis, prior decompensating events were ascites (n = 1, 1 mg BID; n = 5 each per 2 mg BID and 3 mg BID; n = 4, placebo), encephalopathy (n = 1, 1 mg BID; n = 2, 2 mg BID; n = 3, placebo), and variceal bleeding (n = 4, 1 mg BID; n = 1 each per 2 mg BID, 3 mg BID, and placebo). Baseline liver stiffness values were >20 kPa for 83.3% and 72.0% of patients with CP-A and CP-B cirrhosis, respectively, and were >25 kPa for 58.3% and 64.0% of patients with CP-A and CP-B cirrhosis, respectively.During the trial, 1 patient with CP-A cirrhosis (4.2%, placebo) and 3 patients with CP-B cirrhosis (12.0%; n = 1 each per 2 mg BID, 3 mg BID, and placebo) discontinued trial medication: 2 due to an AE (CP-B, n = 1 each per 3 mg BID [delirium] and placebo [hematemesis, non-variceal]) and 2 due to withdrawal by participant (CP-A: n = 1, placebo; CP-B: n = 1, 3 mg BID). All treated patients with CP-A and CP-B cirrhosis and matched HVs were included in the biomarker set and the ECG plasma concentration set, and all patients with CP-A and CP-B cirrhosis and HVs on active treatment were included in the PK parameter analysis.Important protocol deviations were reported for 4 patients with CP-A cirrhosis, 8 patients with CP-B cirrhosis, and 1 HV but did not lead to patient exclusion from the analysis sets. Good compliance with trial medication (80–120%) was recorded for most patients, with exceptions for 2 patients with CP-A cirrhosis (n = 1, 1 mg BID [67.0% on days 1 and 4–9]; n = 1, placebo [50.0% on days 1 and 4–9]) and 2 patients with CP-B cirrhosis (n = 1, 2 mg BID [50% on days 10–15]; n = 1, placebo [75.0% on days 10–15]).