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 language | English |
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Pages (from-to) | 723-729 |
Journal | Cancer Chemotherapy and Pharmacology |
Volume | 76 |
Issue number | 4 |
DOIs | |
Publication status | Published - Oct 2015 |
Keywords
- Olaparib
- Food effect
- Tablet
- PARP inhibition
- PK