Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infections and Compensated Liver Disease

Clin Infect Dis. 2019 Oct 30;69(10):1657-1664. doi: 10.1093/cid/ciz022.

Abstract

Background: Untreated, chronic hepatitis C virus (HCV) infection may lead to progressive liver damage, which can be mitigated by successful treatment. This integrated analysis reports the safety, efficacy, and pharmacokinetics (PK) of the ribavirin-free, direct-acting, antiviral, fixed-dose combination of glecaprevir/pibrentasvir (G/P) in patients with chronic HCV genotype 1-6 infections and compensated liver disease, including patients with chronic kidney disease stages 4 or 5 (CKD 4/5).

Methods: Data from 9 Phase II and III clinical trials, assessing the efficacy and safety of G/P treatment for 8-16 weeks, were included. The presence of cirrhosis was determined at screening using a liver biopsy, transient elastography, or serum biomarkers. The objectives were to evaluate safety, the rate of sustained virologic response at post-treatment week 12 (SVR12), and steady-state PK by cirrhosis status.

Results: Among 2369 patients, 308 (13%) were Child-Pugh Class A, including 20 with CKD 4/5. Overall, <1% of patients experienced an adverse event (AE) that led to G/P discontinuation or G/P-related serious AEs (SAEs). The most common AEs were headache and fatigue, occurring at similar frequencies with and without cirrhosis. SAEs were more common in patients with CKD 4/5, but all were unrelated to G/P. There were no cases of drug-induced liver injury or clinically relevant hepatic decompensation. SVR12 rates were 96.4% (297/308) with compensated cirrhosis and 97.5% (2010/2061) without cirrhosis. PK analysis demonstrated a 2.2-fold increase in glecaprevir exposure, but not pibrentasvir exposure, in patients with compensated cirrhosis.

Conclusions: G/P was safe and efficacious in patients with compensated liver disease, including those with CKD 4/5.

Clinical trials registration: NCT02243280, NCT02243293, NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, and NCT02446717.

Keywords: HCV; adverse event; chronic kidney disease; compensated cirrhosis; glecaprevir/pibrentasvir.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / pharmacokinetics*
  • Data Interpretation, Statistical
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver Cirrhosis / drug therapy
  • Liver Diseases / drug therapy*
  • Liver Diseases / virology
  • Male
  • Quinoxalines / adverse effects
  • Quinoxalines / pharmacokinetics*
  • Sulfonamides / adverse effects
  • Sulfonamides / pharmacokinetics*
  • Sustained Virologic Response

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Quinoxalines
  • Sulfonamides
  • pibrentasvir
  • glecaprevir

Associated data

  • ClinicalTrials.gov/NCT02243280
  • ClinicalTrials.gov/NCT02243293
  • ClinicalTrials.gov/NCT02604017
  • ClinicalTrials.gov/NCT02640482
  • ClinicalTrials.gov/NCT02640157
  • ClinicalTrials.gov/NCT02636595
  • ClinicalTrials.gov/NCT02642432
  • ClinicalTrials.gov/NCT02651194
  • ClinicalTrials.gov/NCT02446717