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

E. Lefebvre, M. Gottwald, K. Lasseter, W. Chang, M. Willett, P. F. Smith, A. Somasunderam, N. S. Utay

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 (AUC0-τ55%, Cmax 29% higher) but were not with mild HI (AUC0-τ 38%, Cmax 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.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalClinical and Translational Science
Volume9
Issue number3
DOIs
StatePublished - Jun 1 2016

Fingerprint

Pharmacokinetics
Safety
Liver
Bacterial Translocation
Biomarkers
TAK-652
Liver Cirrhosis
Blood
Cytokines
Ligands
Inflammation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment. / Lefebvre, E.; Gottwald, M.; Lasseter, K.; Chang, W.; Willett, M.; Smith, P. F.; Somasunderam, A.; Utay, N. S.

In: Clinical and Translational Science, Vol. 9, No. 3, 01.06.2016, p. 139-148.

Research output: Contribution to journalArticle

Lefebvre, E, Gottwald, M, Lasseter, K, Chang, W, Willett, M, Smith, PF, Somasunderam, A & Utay, NS 2016, 'Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment', Clinical and Translational Science, vol. 9, no. 3, pp. 139-148. https://doi.org/10.1111/cts.12397
Lefebvre, E. ; Gottwald, M. ; Lasseter, K. ; Chang, W. ; Willett, M. ; Smith, P. F. ; Somasunderam, A. ; Utay, N. S. / Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment. In: Clinical and Translational Science. 2016 ; Vol. 9, No. 3. pp. 139-148.
@article{14e1034066a140c6a67a4e8b2a8f49b4,
title = "Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment",
abstract = "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 (AUC0-τ55{\%}, Cmax 29{\%} higher) but were not with mild HI (AUC0-τ 38{\%}, Cmax 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.",
author = "E. Lefebvre and M. Gottwald and K. Lasseter and W. Chang and M. Willett and Smith, {P. F.} and A. Somasunderam and Utay, {N. S.}",
year = "2016",
month = "6",
day = "1",
doi = "10.1111/cts.12397",
language = "English (US)",
volume = "9",
pages = "139--148",
journal = "Clinical and Translational Science",
issn = "1752-8054",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment

AU - Lefebvre, E.

AU - Gottwald, M.

AU - Lasseter, K.

AU - Chang, W.

AU - Willett, M.

AU - Smith, P. F.

AU - Somasunderam, A.

AU - Utay, N. S.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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 (AUC0-τ55%, Cmax 29% higher) but were not with mild HI (AUC0-τ 38%, Cmax 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.

AB - 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 (AUC0-τ55%, Cmax 29% higher) but were not with mild HI (AUC0-τ 38%, Cmax 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.

UR - http://www.scopus.com/inward/record.url?scp=85027920092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027920092&partnerID=8YFLogxK

U2 - 10.1111/cts.12397

DO - 10.1111/cts.12397

M3 - Article

VL - 9

SP - 139

EP - 148

JO - Clinical and Translational Science

JF - Clinical and Translational Science

SN - 1752-8054

IS - 3

ER -