Published in:
01-10-2015 | Original Article
Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours
Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015
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Background
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.
Methods
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.
Results
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 ~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 (AUC0–∞) [ratio of geometric means (90 % CI), 1.08 (1.01, 1.16)]. The point estimate and 90 % CI for the AUC0–∞ treatment ratio were within pre-defined bioequivalence limits (0.80–1.25). Adverse event data were consistent with the known safety profile of olaparib.
Conclusions
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.