1ABIVAX, 5 Rue de la Baume, 75008 Paris, France2Centre Cap Montpellier, 9 avenue Charles Flahault, 34094 Montpellier, France3Independent Consultant c/o ABIVAX, 5 Rue de la Baume, Paris, France4Northwestern University Feinberg School of Medicine, 645 N Michigan Avenue, Suite 1058, Chicago, IL 60611, USA5Institut de Génétique Moléculaire, University of Montpellier, 1919 Route de Mende, 34293 Montpellier, France
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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.