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

J Antimicrob Chemother. 2017 Mar 1;72(3):820-828. doi: 10.1093/jac/dkw458.


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/m 2 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 C max was observed approximately 2 h after administration in all groups. ABX464 was rapidly and substantially metabolized into ABX464-NGlc. The C max 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 t 1/2 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Quinolines / adverse effects*
  • Quinolines / pharmacokinetics*
  • Urinalysis


  • ABX464
  • Anti-HIV Agents
  • Quinolines

Associated data