Evacetrapib
Severe hepatic impairment, but not severe renal impairment, raises evacetrapib exposure and prolongs its half-life (Eur J Clin Pharmacol 2016)
Original title: Effect of hepatic or renal impairment on the pharmacokinetics of evacetrapib
Two open-label, parallel-design studies tested how hepatic or renal impairment affects the pharmacokinetics of a single 130 mg evacetrapib dose, comparing normal function to Child-Pugh mild, moderate, or severe hepatic impairment, or to severe renal impairment. Pharmacokinetic parameters were comparable between controls and mildly hepatically impaired subjects, but AUC was greater, half-life longer, and Cmax lower with moderate and severe hepatic impairment, with apparent clearance unchanged in mild impairment but reduced in moderate and severe impairment; Spearman correlation showed no relationship between clearance and Child-Pugh score. In the renal study, AUC and half-life were similar across groups while Cmax was 15% lower with severe impairment, and clearance in severely renally impaired subjects differed by less than 6% from controls, with no relationship to creatinine clearance or glomerular filtration rate. Neither study found clinically significant laboratory changes, and adverse events were low and mild-to-moderate, showing evacetrapib exposure rises progressively with worsening hepatic impairment but is unaffected by severe renal impairment.
Original abstract
Purpose: The aim of this study is to investigate the effect of hepatic or renal impairment on the pharmacokinetics of a single 130-mg evacetrapib dose.
Methods: Two open-label, parallel-design studies in males and females with normal hepatic function or Child-Pugh mild, moderate, or severe hepatic impairment, or with normal renal function or severe renal impairment. Non-compartmental pharmacokinetic parameters were estimated from plasma concentration-time data. Evacetrapib safety and tolerability were assessed.
Results: Pharmacokinetic parameter estimates were comparable between controls and mildly hepatically impaired subjects. Geometric mean area under the concentration-time curve (AUC) was greater, half-life (t1/2) was longer, and maximum concentration (Cmax) was lower in subjects with moderate and severe hepatic impairment than in controls. Apparent clearance (CL/F) did not differ between controls and those with mild hepatic impairment, but CL/F decreased for moderate and severe impairment. Spearman correlation coefficient showed no relationship between CL/F and Child-Pugh score. In the renal study, AUC and t1/2 were similar between groups, while Cmax was 15 % lower in subjects with severe impairment. CL/F in severely renally impaired subjects differed by <6 % from that in controls. Spearman correlation coefficient showed no apparent relationship between CL/F and estimated creatinine clearance or glomerular filtration rate. Neither study noted changes in clinical laboratory parameters or clinically significant findings. Adverse event incidence was low, and all were mild or moderate in severity.
Conclusion: Evacetrapib exposure did not differ between mild hepatic impairment and normal hepatic function, but increased along the progression from mild to moderate to severe hepatic impairment. Severe renal impairment did not affect evacetrapib exposure.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.