Author information
1
Merck & Co., Inc., 8000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
2
Merck & Co., Inc., 8000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. hwa-ping.feng@merck.com.
3
Clinical Pharmacology of Miami, 550 West 84th Street, Miami, FL, 33014, USA.
4
Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
5
Orlando Clinical Research Center, 5055 South Orange Avenue, Orlando, FL, 32809, USA.
Abstract
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 (C max), respectively. The observed median time to C max 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.