Plasma, urine and skin PK
Serial venous blood
SKIN
Serial venous blood sampling (6 ml) and 24-h urine collections for quantification of KT-474 were performed on intensive PK sampling days. Skin biopsy samples were collected in MAD and open-label portions of the study and used for the quantification of KT-474 concentrations. Concentrations of KT-474 in plasma and urine were measured using validated liquid chromatography with tandem mass spectrometry (LC–MS/MS) assays with a lower limit of quantification (LLOQ) of 0.150 ng mlPK parameters for KT-474 were estimated from plasma and urine concentration data via non-compartmental analysis using Phoenix WinNonlin (version 8.3.2, Certara).