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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 Cmax and 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 Cmax increased 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.).

SUBMITTER: Scherrer D

PROVIDER: S-EPMC5192114 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Randomized Trial of Food Effect on Pharmacokinetic Parameters of ABX464 Administered Orally to Healthy Male Subjects.

Scherrer Didier D Rouzier Regine R Cardona Marine M Barrett P Noel PN Steens Jean-Marc JM Gineste Paul P Murphy Robert L RL Tazi Jamal J Ehrlich Hartmut J HJ

Antimicrobial agents and chemotherapy 20161227 1

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 (C<sub>max</sub>) and the area under the con ...[more]

PMID: 27799203

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Project description:Background and objectiveRosuvastatin and ezetimibe are commonly applied in lipid-lowering pharmacotherapy. However, the pharmacokinetic (PK) interaction was not clear by the coadministration of rosuvastatin and ezetimibe. This study investigated the pharmacodynamic (PD) and PK interactions between rosuvastatin and ezetimibe through a crossover clinical trial.Subjects and methodsA randomized, open-label, multiple-dose, two-treatment, two-period, two-sequence crossover study with two treatment parts was conducted in healthy male subjects. Study part A involved rosuvastatin, and study part B involved ezetimibe. A total of 25 subjects in both parts completed the PK and PD evaluations. Rosuvastatin (20 mg) or ezetimibe (10 mg) was administered once daily for 7 days as monotherapy or co-therapy. The plasma concentrations of rosuvastatin, total ezetimibe and free ezetimibe were measured for 72 h after day 7. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) were investigated for the PD assessments on day 1 (pretreatment) and day 8.ResultsRosuvastatin and ezetimibe presented multiple peaks. The 90% confidence intervals (CIs) of the geometric mean ratios for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve during the dosing interval at steady state (AUCτ,ss) of rosuvastatin and total ezetimibe were within the range 0.8-1.25. However, the coadministration increased the systemic exposure of free ezetimibe. In the PD assessments, rosuvastatin and ezetimibe monotherapy reduced the LDL-C and TC levels effectively. In addition, the lipid-lowering effects of the coadministration corresponded to an approximate summation of the effects of rosuvastatin and ezetimibe monotherapy. However, no significant changes in HDL-C were observed with rosuvastatin or ezetimibe treatment. No significant safety issue was noted.ConclusionThe coadministration of rosuvastatin and ezetimibe revealed a bioequivalent PK interaction. Additional lipid-lowering effects, including decreased LDL-C and TC, were observed as expected in combination therapy without significant safety concern.

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Randomized Trial of Food Effect on Pharmacokinetic Parameters of ABX464 Administered Orally to Healthy Male Subjects.

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Randomized Trial of Food Effect on Pharmacokinetic Parameters of ABX464 Administered Orally to Healthy Male Subjects.

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