title: Randomized Trial of Food Effect on Pharmacokinetic Parameters of ABX464 Administered Orally to Healthy Male Subjects.
abstract: ABX464 is an antiviral that provides a novel approach to the reduction and control of HIV infection. Investigation of food influence is important in the optimization of treatment. An open-label, food effect, randomized study which included 2 groups of 24 subjects each was carried out to assess the bioavailability and safety of single (group 1) and repeated (group 2) oral doses of ABX464 (50 mg) under fed or fasted conditions. The maximum concentration (Cmax) and the area under the concentration-time curve from time zero to infinity (AUC0-∞) of ABX464 were demonstrated to increase with food after a single dose of ABX464 (219% and 188%, respectively). The apparent terminal elimination half-lives (t1/2s) under fed and fasted conditions were comparable, at about 0.80 h. The median time to maximum concentration (Tmax) was delayed from 1.5 to 2.8 h, and the ratio of the AUC0-∞obtained under fed conditions to the AUC0-∞obtained under fasted conditions (Frel) was 2.69. Comparable results were obtained on day 1 and day 10 in group 2. The increases in Cmaxand AUC0-∞of the metabolite ABX464-N-glucuronide (ABX464-NGlc) were, however, much more limited when ABX464 was given with food. The t1/2s were also comparable under the two conditions (around 100 h). Between day 1 and day 10, the Cmaxincreased by 5% under the fasted condition and by 25% under the fed condition. The most common related treatment-emergent adverse events were headaches, vomiting, and nausea. It was concluded that food has a significant impact on the levels of ABX464 in plasma with a delay in absorption and increased relative bioavailability, with a lesser impact on its biotransformation into ABX464-NGlc. ABX464 was well tolerated under both fasted and fed conditions. (This study has been registered at ClinicalTrials.gov under registration no. NCT02731885.).
authors: Abivax, Paris, France.
authors: Didier
authors: D
authors: Scherrer
authors: CAP Research, Phoenix, Mauritius.
authors: Regine
authors: R
authors: Rouzier
authors: CAP Research, Phoenix, Mauritius.
authors: Marine
authors: M
authors: Cardona
authors: Independent Consultant, Paris, France.
authors: P Noel
authors: PN
authors: Barrett
authors: Abivax, Paris, France.
authors: Jean-Marc
authors: JM
authors: Steens
authors: Abivax, Paris, France paul.gineste@abivax.com.
authors: Paul
authors: P
authors: Gineste
authors: Northwestern University, Chicago, Illinois, USA.
authors: Robert L
authors: RL
authors: Murphy
authors: Institut de Génétique Moléculaire, University of Montpellier, Montpellier, France.
authors: Jamal
authors: J
authors: Tazi
authors: Abivax, Paris, France.
authors: Hartmut J
authors: HJ
authors: Ehrlich
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D015992:Body Mass Index; D018565:Food-Drug Interactions; D020719:Glucuronides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D020719:Glucuronides
keywords: ABX464; HIV; food effect; human immunodeficiency virus; pharmacokinetics; safety