Table. 3.

Laboratory parameters—normal ranges/clinically acceptable ranges

First-in-human trials

•Relevant hepatic parameter not to exceed ULN: ALT, AST, bilirubin (except in case of Gilbert’s disease*) *In case of Gilbert’s disease, elevated bilirubin not clinically relevant, yet may hamper interpretation of potential drug effects • Relevant renal parameters not to exceed ULN: creatinine, estimated GFR according to suitable formulae • Amylase and lipase to be interpreted in clinical context • Protocol to present rationale whether additional laboratory parameters required not to exceed reference ranges

Trials with ‘clinically established IMPs’ (e.g. bioequivalence trials for generic medicines applications)

• Slight elevation acceptable for hepatic parameters if no indication of apparent disease: 10% above ULN for ALT, 20% above ULN for AST or bilirubin (except in case of Gilbert’s disease*) *In case of Gilbert’s disease, see above • Slight elevation (10%) acceptable for renal parameters (except for creatinine**) if no indication of apparent disease **As creatinine especially in healthy male subjects also may reflect physical activity, protein intake by food, body height and muscle mass, some authors deem a slight elevation of creatinine up to 0.1 mg/dL above ULN as acceptable • Protocol to present rationale why these abnormal laboratory parameters seem acceptable

IMP investigational medicinal product, ALT alanine aminotransferase, AST aspartate aminotransferase, AP alkaline phosphatase, GGT gamma-glutamyltransferase, ULN upper limit of normal, GFR glomerular filtration rate