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

Edward Gane, Fred Poordad, Neddie Zadeikis, Joaquin Valdes, Chih Wei Lin, Wei Liu, Armen Asatryan, Stanley Wang, Catherine Stedman, Susan Greenbloom, Tuan Nguyen, Magdy Elkhashab, Marcus Alexander Wörns, Albert Tran, Jean Pierre Mulkay, Carolyn Setze, Yao Yu, Tami Pilot-Matias, Ariel Porcalla, Federico J. Mensa

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)1657-1664
Number of pages8
JournalClinical Infectious Diseases
Volume69
Issue number10
DOIs
StatePublished - Nov 15 2019

Keywords

  • HCV
  • adverse event
  • chronic kidney disease
  • compensated cirrhosis
  • glecaprevir/pibrentasvir

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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