gdc-0068 and Liver-Failure

Ipatasertib is a highly selective small-molecule pan-Akt inhibitor in clinical development. Ipatasertib is predominantly eliminated by the liver, and therefore, the effect of hepatic impairment on ipatasertib pharmacokinetics (PK) was evaluated. In this phase 1 open-label, parallel group study, the PK of ipatasertib were evaluated in subjects with hepatic impairment based on both the Child-Pugh and the National Cancer Institute Organ Dysfunction Working Group classification for hepatic impairment. A single dose of ipatasertib at 100 mg was administered and the PK was characterized in healthy subjects with normal hepatic function or mild, moderate, and severe hepatic impairment. Based on Child-Pugh classification, subjects with moderate and severe hepatic impairment had an ≈2- and 3-fold increase in systemic exposure (area under the plasma concentration-time curve from time 0 to infinity [AUC

Topics: Adult; Aged; Antineoplastic Agents; Area Under Curve; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Liver Failure; Male; Metabolic Clearance Rate; Middle Aged; Patient Acuity; Piperazines; Pyrimidines