Pharmacokinetics and tolerability of ABX464, a novel first-in-class compound to treat HIV infection, in healthy HIV-uninfected subjects

Didier Scherrer, Regine Rouzier, P. Noel Barrett, Jean Marc Steens, Paul Gineste, Robert L. Murphy, Jamal Tazi, Hartmut J. Ehrlich

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Background: An anti-HIV compound (ABX464) has been developed with a novel mechanism of activity in that it blocks viral gene expression in cells that are already infected. Objectives: A first-in-man study was conducted to determine the pharmacokinetic and safety profiles of ABX464. This was carried out as an open label, parallel group, single ascending dose, exploratory study. Methods: Twenty-four male subjects in good health without HIV infection, aged from 18 to 55 years old, with BMIs of 18-27 kg/m2 were included. A single oral dose of ABX464 (50, 100, 150 or 200 mg) was administered on the morning of day 0 after overnight fasting, with follow-up for 45 days. Safety assessments consisted of vital signs, electrocardiogram, physical examination, laboratory tests and urinalysis. Pharmacokinetic parameters were calculated for ABX464 and its main metabolite ABX-464-N-glucuronide (ABX464-NGlc). The study was registered at https://www.clinicaltrials (trial number NCT02792686). Results: ABX464 was well tolerated; the most frequent related treatment-emergent adverse events were headaches, nausea and vomiting; they were not considered as treatment-limiting effects. ABX464's Cmax was observed approximately 2 h after administration in all groups. ABX464 was rapidly and substantially metabolized into ABX464-NGlc. The Cmax of ABX464-NGlc was observed approximately 4 h post-dose and was about 160-fold higher than that of the parent with a much longer t1/2 (90-110 h). The ratio of metabolite to parent drug was consistent across the complete dose range. Conclusions: These studies confirmed that ABX464 is well tolerated and rapidly and substantially metabolized into ABX464-NGlc in human subjects.

Original languageEnglish (US)
Pages (from-to)820-828
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Issue number3
StatePublished - Mar 1 2017

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)


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