Effects of food and ethnicity on the pharmacokinetics of venadaparib, a next-generation PARP inhibitor, in healthy Korean, Caucasian, and Chinese male subjects

TL;DR

This study found that food and ethnicity do not significantly affect the absorption and safety of venadaparib, a new cancer drug, in healthy men from different ethnic backgrounds.

Contribution

The study provides new evidence on the pharmacokinetic consistency of venadaparib across ethnicities and food states.

Findings

Venadaparib's systemic exposure was not significantly affected by a high-fat meal.

Pharmacokinetic profiles were comparable among Korean, Caucasian, and Chinese subjects.

Venadaparib was safe and well-tolerated in both fasted and fed states.

Abstract

Venadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Caucasian, and Chinese male subjects.

In this randomized, open-label, single-dose, two-sequence, two-period, and crossover study, Korean and Caucasian subjects received venadaparib 80 mg in each period (fasted or fed state) with a seven-day washout. In an open-label, single-dose study, Chinese subjects received venadaparib 80 mg only in the fasted state. Serial blood samples were collected up to 72 h post-dosing.

Twelve subjects from each ethnic group completed the study. The geometric mean ratios (90% confidence intervals) of the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the last measurable time point (AUClast) of venadaparib for the fed to fasted state were 0.82 (0.7457–0.9094) and 1.02 (0.9088–1.1339) in Koreans, and 0.77 (0.6871–0.8609) and 0.96 (0.9017–1.0186) in Caucasians, respectively. No statistically significant differences were observed in Cmax (P-value = 0.45) or AUClast (P-value = 0.30) among the three ethnic groups. A single venadaparib dose was well-tolerated.

The overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased Cmax in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states.

The online version contains supplementary material available at 10.1007/s10637-023-01405-z.

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