Bioequivalence Study of Crushed Elbasvir/Grazoprevir Compared to the Whole Tablet
Status:
Completed
Trial end date:
2019-07-30
Target enrollment:
Participant gender:
Summary
Elbasvir/grazoprevir (Zepatier®) is a once-daily tablet for the treatment of chronic
hepatitis C virus (HCV) GT1a, 1b or 4 infection containing the NS5A inhibitor elbasvir (ELB)
50 mg and the NS3/4A protease inhibitor grazoprevir (GZR) 100 mg.
For patients with swallowing difficulties, administration of whole tablets can be
problematic. In addition, HCV patients that are hospitalized (at intensive care units) due to
severe illness (co-infections/ liver failure) might not be able to swallow medication.
Therefore it is useful to know whether it is possible to administer ELB/GZR through a
different route, like a feeding tube.
In daily practice, information about the safety and efficacy of crushed tablets is lacking
which might result in noncompliance, interruption or discontinuation of expensive HCV
therapy. However, it is not recommended to interrupt treatment because there is no evidence
about the efficacy of the therapy after discontinuation (and restarting).
Currently, patients and healthcare professionals are crushing tablets without information
about efficacy and safety. Depending on the biopharmaceutical characteristics of a drug
formulation, crushing tablets can lead to altered pharmacokinetics of drugs.
It is important to know whether pharmacokinetic parameters are influenced by crushing of
tablets; both a decrease and an increase in exposure may occur. A decrease of the plasma
concentrations of ELB and/or GZR potentially reduces the therapeutic effect of the drugs.
Higher doses or switching to other HCV-drugs might be needed. In contrast, in case a higher
Cmax and/or AUC occurs there might be an increased risk of toxicity.
As a result, crushing the drug is a contra-indication based on the available data. Therefore
this study will be conducted to investigate whether a crushed ELB/GZR tablet is bioequivalent
to ELB/GZR as a whole tablet.