Outcomes {12}
liver stiffness, syncope, hypotension
ADVERSE EVENT, EVENTS, SECONDARY, INSULIN RESISTANCE
The primary endpoint for each trial is the percentage change in HVPG from baseline after 24 weeks (1366.0021) or 8 weeks (1366.0029) of treatment. Secondary endpoints are the percentage change in HVPG from baseline after 8 weeks (1366.0021 trial only); response defined as a >10% reduction in HVPG from baseline; occurrence of Common Terminology Criteria for Adverse Events grade ≥ 3 hypotension or syncope or discontinuation due to hypotension or syncope; and the occurrence of one or more decompensation events. Each secondary endpoint will be assessed after 8 weeks in both trials and after 24 weeks in the 1366.0021 trial.Further endpoints in both trials include (but are not limited to) change from baseline in spleen stiffness, liver fat content and liver stiffness by transient elastography, hepatic function (measured by prothrombin time/international normalised ratio, activated partial prothrombin time, bilirubin, liver enzymes [alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase and alkaline phosphatase] and albumin), renal function (measured by eGFR) and disease-specific and mode-of-action exploratory biomarkers.In the 1366.0021 trial, the change from baseline in further endpoints will be assessed at the main time points (8 and 24 weeks) and will be measured at additional time points as defined in Table In the 1366.0029 trial, all further endpoints will be assessed after 8 weeks of treatment. This trial will also assess the change from baseline in metabolic function (measured by HbA1c, serum glucose and Homeostatic Model Assessment for Insulin Resistance), bodyweight and hepatic function (measured by systemic hepatic filtration rate and portal hepatic filtration rate).Plasma concentrations of BI 685509 and, if feasible, further PK endpoints will be determined in both trials: maximum concentration (C