Merck & Co., Inc., 8000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
Merck & Co., Inc., 8000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. firstname.lastname@example.org.
Clinical Pharmacology of Miami, 550 West 84th Street, Miami, FL, 33014, USA.
Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
Orlando Clinical Research Center, 5055 South Orange Avenue, Orlando, FL, 32809, USA.
The combination of elbasvir and grazoprevir is approved for the treatment of hepatitis C virus genotype 1 or 4 infection.
To evaluate the pharmacokinetics and safety of single-dose elbasvir 50 mg in participants with hepatic impairment.
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.
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.
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.