Background and Objective
Glecaprevir and pibrentasvir are pangenotypic direct-acting antiviral agents for the treatment of chronic hepatitis C virus infection. The aim of the present study was to evaluate the drug–drug interaction and safety of glecaprevir and pibrentasvir coadministration in healthy volunteers.
In this open-label, randomized, multiple-dose, Phase 1 study in 72 subjects, glecaprevir (100–1200 mg once daily) and pibrentasvir (40–200 mg once daily) were administered alone for 7 days and then in combination for another 7 days. Intensive blood sampling was performed on Days 1, 7, 8, and 14, and pharmacokinetic interactions were assessed using a repeated measures analysis of glecaprevir and pibrentasvir maximum plasma concentration (C max) and area under the curve (AUC).
Coadministration of glecaprevir 400 mg increased pibrentasvir 120 and 40 mg steady-state C max and AUC values to 2.9–6.3-fold, and coadministration of glecaprevir 700 mg increased pibrentasvir 160 mg steady-state C max and AUC24 values to up to sevenfold of the values when pibrentasvir was administered alone. Glecaprevir C max and AUC values during coadministration were less than 1.5-fold of the values when glecaprevir was administered alone. The combination of glecaprevir and pibrentasvir at doses up to 400 mg was well tolerated by the healthy subjects in this study. High glecaprevir exposures at 700 and 1200 mg were associated with grade 2/3 elevations in alanine aminotransferase, aspartate aminotransferase, and/or bilirubin.
Coadministration of pibrentasvir 120 mg with glecaprevir doses up to 400 mg resulted in increases in pibrentasvir exposures without significant changes in glecaprevir exposures in the absence of any clinically significant laboratory abnormalities.
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The study was sponsored by AbbVie. AbbVie contributed to the study design, research, and interpretation of data, and the writing, reviewing, and approving of the publication. The authors thank the clinical sites and investigators and the AbbVie study team members for assistance in the conduct of the study, and the AbbVie Drug Analysis Department for supporting drug assay development and drug analysis. Medical writing support was provided by Allison Kitten, PhD, and Amy Rohrlack, BS, employees of AbbVie.
The study was sponsored by AbbVie. AbbVie contributed to the study design, research, and interpretation of data, and the writing, reviewing, and approving of the publication.
Conflict of interest
CL, WZ, AA, AC, and WL are employees of AbbVie and may hold AbbVie stock or stock options. SD is a former employee of AbbVie and may hold AbbVie stock or stock options. Medical writing support was provided by Allison Kitten and Amy Rohrlack, employees of AbbVie.
Research involving human participants
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was approved by the institutional review board (Vista Medical Center East Institutional Review Board, Waukegan, IL, USA).
Informed consent was obtained from all individual participants included in the study.
Sandeep Dutta is a former employee of AbbVie, Inc.
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Lin, C., Dutta, S., Zhao, W. et al. Pharmacokinetic Interactions and Safety of Coadministration of Glecaprevir and Pibrentasvir in Healthy Volunteers. Eur J Drug Metab Pharmacokinet 43, 81–90 (2018). https://doi.org/10.1007/s13318-017-0428-8