title: Pharmacokinetics and tolerability of ABX464, a novel first-in-class compound to treat HIV infection, in healthy HIV-uninfected subjects.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  These studies confirmed that ABX464 is well tolerated and rapidly and substantially metabolized into ABX464-NGlc in human subjects.
authors.affiliation: ABIVAX, 5 Rue de la Baume, 75008 Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Scherrer
authors.affiliation: Centre Cap Montpellier, 9 avenue Charles Flahault, 34094 Montpellier, France.
authors.forename: Regine
authors.initials: R
authors.lastname: Rouzier
authors.affiliation: Independent Consultant c/o ABIVAX, 5 Rue de la Baume, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Noel Barrett
authors.affiliation: ABIVAX, 5 Rue de la Baume, 75008 Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Steens
authors.affiliation: ABIVAX, 5 Rue de la Baume, 75008 Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Gineste
authors.affiliation: Northwestern University Feinberg School of Medicine, 645 N Michigan Avenue, Suite 1058, Chicago, IL 60611, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.affiliation: Institut de Génétique Moléculaire, University of Montpellier, 1919 Route de Mende, 34293 Montpellier, France.
authors.forename: Jamal
authors.initials: J
authors.lastname: Tazi
authors.affiliation: ABIVAX, 5 Rue de la Baume, 75008 Paris, France.
authors.forename: Hartmut J
authors.initials: HJ
authors.lastname: Ehrlich
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000009:adverse effects* / Q000493:pharmacokinetics*; D016482:Urinalysis
chemical_list: C000623073:ABX464; D019380:Anti-HIV Agents; D011804:Quinolines