EVG/COBI/FTC/TAF Bioequivalence Comparing Whole Tablets with Tablets Dissolved in Tap Water

Adriana Andrade, Edward J. Fuchs, Mark A. Marzinke, Sandra Abdul Massih, Jennifer Breakey, Sasha Beselman, Ian McNicholl, Craig W. Hendrix

Research output: Contribution to journalArticlepeer-review

Abstract

Medication adherence can be challenging for persons with difficulty swallowing tablets. We investigated the bioequivalence of a dissolved tablet when compared with that of a whole tablet of the fixed-dose combination elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir (TFV) alafenamide fumarate (TAF). A within-subject fixed-order two-period open-label study was conducted in 12 HIV-negative research participants after obtaining informed consent. Participants took a single dose each of the whole tablet and dissolved tablet under direct observation, separated by a 14-day washout period. The dissolved tablet was prepared by adding one whole EVG/COBI/FTC/TAF tablet to 120 mL tap water and stirring. Both dosage types were taken with a standardized meal. Plasma samples were obtained for 72 h postdose. Plasma EVG, FTC, TAF, and TFV were analyzed with liquid chromatographic-Tandem mass spectrometric methods. Peak plasma concentration (Cmax) and the area under the concentration-Time curve extrapolated to infinity (AUC0-∞) were estimated using WinNonlin software (v.8.3). The primary outcome was bioequivalence consistent with FDA guidance using the 90% confidence interval or the geometric mean ratio. Of 12 participants, 7 were black (58%) and 5 were white (42%), 4 were women (33%), 8 were men (67%), and the mean age was 43.6 years (23-54). There were no complaints about taste with the dissolved tablet. Bioequivalence was established only for FTC. EVG Cmax and AUC0-∞ were higher by 18% and 12%, respectively, when taking the dissolved compared with the whole tablet. TAF AUC0-∞ and Cmax were both 8% lower, whereas TFV Cmax and AUC0-∞ were 8% and 5% lower, respectively, when taken after dissolution. EVG/COBI/FTC/TAF dissolved rapidly in water and had no unpleasant taste. Increases in EVG and decreases in TAF and TFV concentrations were observed when taking dissolved EVG/COBI/FTC/TAF. These changes were judged to be clinically insignificant. Dissolving EVG/COBI/FTC/TAF in water may be suitable for those with pill swallowing challenges. The trial was registered on (//clinicaltrials.gov NCT03717129).

Original languageEnglish (US)
Pages (from-to)38-43
Number of pages6
JournalAIDS research and human retroviruses
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2023

Keywords

  • HIV treatment
  • antiretroviral
  • bioequivalence
  • elvitegravir
  • emtricitabine
  • tenofovir

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology
  • Immunology

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