The rationale and study design of two phase II trials examining the effects of BI 685509, a soluble guanylyl cyclase activator, on clinically significant portal hypertension in patients with compensated cirrhosis

Table 3 Safety and key exploratory biomarkers

Parameter	Specific measure
Safety laboratory measurements of liver function	PT/INR aPTT Bilirubin (direct and indirect) Liver enzymes (ALT, AST, γGT and alkaline phosphatase) Albumin Ferritin
Composite scores of advanced liver disease	Fibrosis-4 index FibroScan®-AST score FibroScan®-based scores for advanced fibrosis (agile 3 +) and indicative of liver cirrhosis (agile 4)* MELD MELD-Na ELF score NIS4™ score
Cardiac and renal biomarkers	BNP* Troponin I eGFR Creatinine
Fibrosis markers	Hyaluronic acid Procollagen III amino-terminal peptide TIMP1 Pro-C3 Pro-C6*
Inflammation and cell death biomarkers	hs-CRP Alpha 2 macroglobulin CK18 M30 CK18 M65 CK19 fragment CYFRA21-1
Metabolic function biomarkers	Apolipoprotein A1 HbA1c* Serum glucose HOMA-IR*
Alcohol abuse biomarker^§	Phosphatidylethanol
Bile acid panel	AbsoluteIDQ® bile acids kit (Biocrates) covering 20 bile acids
miRNA profiling	RNA sequencing from plasma
Pharmacogenetics	Known genetic variants such as rs738409 (in PNPLA3) and rs58542926 (in TM6SF2)

^*Assessed in the 1366.0029 trial only
^§Assessed in the 1366.0021 trial only
γGT gamma-glutamyl transferase, ALT alanine aminotransferase, aPTT activated partial thromboplastin time, AST aspartate aminotransferase, BNP brain natriuretic peptide, CK18 M30 caspase-cleaved cytokeratin 18, CK18 M65 total cytokeratin 18, CK19 cytokeratin 19, eGFR estimated glomerular filtration rate, ELF enhanced liver fibrosis, HOMA-IR Homeostatic Model Assessment for Insulin Resistance, hs-CRP high-sensitivity C-reactive protein, MELD Model for End-Stage Liver Disease, MELD-Na Model for End-Stage Liver Disease-sodium, Pro-C3 amino-terminal propeptide of type III collagen, Pro-C6 propeptide of type VI collagen, PT/INR prothrombin time/international internalised ratio, TIMP1 tissue inhibitor of metalloproteinase 1

ISSN: 1745-6215