Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment

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• 作者：E Lefebvre ; M Gottwald ; K Lasseter ; W Chang ; M Willett ; PF Smith ; A Somasunderam and NS Utay
• 刊名：Clinical and Translational Science
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：9
• 期：3
• 页码：139-148
• 全文大小：646K
• ISSN：1752-8062

文摘

Cenicriviroc, a dual CCR2/CCR5 antagonist, is being evaluated for treatment of nonalcoholic steatohepatitis and liver fibrosis (CENTAUR; NCT02217475). As it is metabolized by the liver, cenicriviroc was investigated in hepatic-impaired participants for pharmacokinetic changes. Participants with mild-to-moderate hepatic impairment (HI) (Child–Pugh class A (N = 7) or B (N = 8)) and matched controls (N = 15) received cenicriviroc 150 mg once daily for 14 days. Serial blood samples were obtained on Days 1 and 14. Safety, tolerability, and effects on CCR2/CCR5 ligands, cytokines, and bacterial translocation biomarkers were evaluated. Cenicriviroc exposures were increased by moderate HI (AUC_0-τ 55%, C_max 29% higher) but were not with mild HI (AUC_0-τ 38%, C_max 40% lower). Cenicriviroc was well tolerated. Rapid and potent CCR2/CCR5 blockade was observed, not associated with increases in hepatic inflammation or bacterial translocation biomarkers. Study findings suggest that cenicriviroc 150 mg can be used in patients with mild-to-moderate HI.