Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment

Kimberly K. Adkison, Jianjun Gan, Lucinda Elko-Simms, Stephen Gardner, Etienne Dumont, Lori S. Jones, Joanne Saunders, Thomas Marbury, William Smith, Jolene Berg, Christopher Galloway, Patrick J. Stump

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

JNJ-56914845 (GSK2336805) is a hepatitis C virus nonstructural protein 5A inhibitor under development for the treatment of chronic hepatitis C (CHC) infection. This open-label, parallel-group, 2-part study evaluated the pharmacokinetics and safety of a single oral 60 mg dose of JNJ-56914845 in 4 cohorts: healthy, mild, moderate, and severe hepatic impairment (n=8/cohort). Severity of hepatic impairment was categorized using Child-Pugh score, and the healthy subjects were matched for age, sex, body mass index, and smoking status to the moderate hepatic impairment cohort. JNJ-56914845 plasma AUC0- was 26%, 52%, and 45% lower in subjects with mild, moderate, and severe hepatic impairment, respectively, relative to healthy subjects with no difference in half-life among the groups. The apparent oral clearance and volume of distribution were higher in subjects with hepatic impairment. The lower plasma concentrations were largely explained by decreased plasma protein binding in hepatically impaired subjects. One subject with severe hepatic impairment had 2 non-drug-related serious adverse events: an esophageal bleed requiring hospitalization, encephalopathy. Although hepatically impaired subjects have lower exposures than healthy matched controls, they had similar or slightly higher exposures than those observed in past studies of noncirrhotic, CHC patients, suggesting that no dose adjustments for hepatic impairment will be needed.

Original languageEnglish (US)
Pages (from-to)1042-1050
Number of pages9
JournalJournal of clinical pharmacology
Volume55
Issue number9
DOIs
StatePublished - Sep 1 2015

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Hepacivirus
Pharmacokinetics
Liver
Chronic Hepatitis C
Healthy Volunteers
Brain Diseases
GSK2336805
Protein Binding
Half-Life
Blood Proteins
Hospitalization
Body Mass Index
Smoking
Safety
Infection

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Adkison, K. K., Gan, J., Elko-Simms, L., Gardner, S., Dumont, E., Jones, L. S., ... Stump, P. J. (2015). Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment. Journal of clinical pharmacology, 55(9), 1042-1050. https://doi.org/10.1002/jcph.512

Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment. / Adkison, Kimberly K.; Gan, Jianjun; Elko-Simms, Lucinda; Gardner, Stephen; Dumont, Etienne; Jones, Lori S.; Saunders, Joanne; Marbury, Thomas; Smith, William; Berg, Jolene; Galloway, Christopher; Stump, Patrick J.

In: Journal of clinical pharmacology, Vol. 55, No. 9, 01.09.2015, p. 1042-1050.

Research output: Contribution to journalArticle

Adkison, KK, Gan, J, Elko-Simms, L, Gardner, S, Dumont, E, Jones, LS, Saunders, J, Marbury, T, Smith, W, Berg, J, Galloway, C & Stump, PJ 2015, 'Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment', Journal of clinical pharmacology, vol. 55, no. 9, pp. 1042-1050. https://doi.org/10.1002/jcph.512
Adkison, Kimberly K. ; Gan, Jianjun ; Elko-Simms, Lucinda ; Gardner, Stephen ; Dumont, Etienne ; Jones, Lori S. ; Saunders, Joanne ; Marbury, Thomas ; Smith, William ; Berg, Jolene ; Galloway, Christopher ; Stump, Patrick J. / Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment. In: Journal of clinical pharmacology. 2015 ; Vol. 55, No. 9. pp. 1042-1050.
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