Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours

Ruth Plummer*, Helen Swaisland, Karin Leunen, Carla M. L. van Herpen, Guy Jerusalem, Jacques De Greve, Martijn P. Lolkema, Patricia Soetekouw, Morten Mau-Sorensen, Dorte Nielsen, James Spicer, Anitra Fielding, Karen So, Wendy Bannister, L. Rhoda Molife

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

36 Citations (Web of Science)

Abstract

The oral PARP inhibitor olaparib has shown efficacy in patients with BRCA-mutated cancer. This Phase I, open-label, three-part study (Parts A-C) in patients with advanced solid tumours evaluated the effect of food on the pharmacokinetics (PK) of olaparib when administered in tablet formulation. PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed. In Part B, patients received olaparib tablets (300 mg bid) for 5 days under fasting conditions; in Part C, patients were allowed continued access to olaparib. Safety was assessed throughout, with data reported for Parts A and B. A total of 60 and 56 patients were evaluable for safety and PK analyses, respectively; 57 patients entered Part B. Rate of olaparib absorption was slower in the presence of food (t (max) delayed by 2.5 h), resulting in a statistically significant similar to 21 % decrease in peak plasma exposure (C (max)) [ratio of geometric means (90 % CI), 0.79 (0.72, 0.86)] but only a marginal increase in olaparib absorption (AUC(0-a)) [ratio of geometric means (90 % CI), 1.08 (1.01, 1.16)]. The point estimate and 90 % CI for the AUC(0-a) treatment ratio were within pre-defined bioequivalence limits (0.80-1.25). Adverse event data were consistent with the known safety profile of olaparib. Results of this study showed that a high-fat meal decreases the rate of absorption and peak exposure to olaparib 300 mg tablets, although in the absence of an effect on the extent of olaparib absorption.
Original languageEnglish
Pages (from-to)723-729
JournalCancer Chemotherapy and Pharmacology
Volume76
Issue number4
DOIs
Publication statusPublished - Oct 2015

Keywords

  • Olaparib
  • Food effect
  • Tablet
  • PARP inhibition
  • PK

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