Background: The combination of elbasvir and grazoprevir is approved for the treatment of hepatitis C virus genotype 1 or 4 infection. Objective: To evaluate the pharmacokinetics and safety of single-dose elbasvir 50 mg in participants with hepatic impairment. Methods: Participants with mild, moderate, or severe hepatic impairment and age-, sex-, and weight-matched healthy controls were enrolled in a 3-part, open-label, sequential-panel, single-dose pharmacokinetic study. Blood samples were collected to assess pharmacokinetics. Safety and tolerability were assessed throughout the study. Results: Thirty-four participants were enrolled: eight with mild hepatic impairment, 11 with moderate hepatic impairment, seven with severe hepatic impairment, and eight healthy matched controls. Participants with mild, moderate, and severe hepatic impairment demonstrated a numeric, but not statistically significant, decrease in elbasvir exposure compared with controls, with a mean 39, 28, and 12% decrease in area under the concentration–time curve from time 0 extrapolated to infinity, as well as a 42, 31, and 42% decrease in maximum plasma concentration (Cmax), respectively. The observed median time to Cmax was similar in participants with hepatic impairment and controls. Single-dose administration of elbasvir was well tolerated. Conclusions: The pharmacokinetics of elbasvir after a single, oral 50-mg dose were not clinically meaningfully altered in non–HCV-infected participants with mild, moderate, or severe hepatic dysfunction. However, since elbasvir is currently available only as part of a fixed-dose combination with grazoprevir, the fixed-dose combination should not be administered to patients with moderate or severe hepatic impairment, due to the significantly increased plasma grazoprevir exposures in those populations.
|Original language||English (US)|
|Number of pages||9|
|Journal||European Journal of Drug Metabolism and Pharmacokinetics|
|State||Accepted/In press - Dec 15 2017|
ASJC Scopus subject areas
- Pharmacology (medical)