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

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

Author information

1
ABIVAX, 5 Rue de la Baume, 75008 Paris, France.
2
Centre Cap Montpellier, 9 avenue Charles Flahault, 34094 Montpellier, France.
3
Independent Consultant c/o ABIVAX, 5 Rue de la Baume, Paris, France.
4
Northwestern University Feinberg School of Medicine, 645 N Michigan Avenue, Suite 1058, Chicago, IL 60611, USA.
5
Institut de Génétique Moléculaire, University of Montpellier, 1919 Route de Mende, 34293 Montpellier, France.

Abstract

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.

PMID:
27999038
DOI:
10.1093/jac/dkw458
[Indexed for MEDLINE]

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