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

Cancer Chemother Pharmacol. 2015 Oct;76(4):723-9. doi: 10.1007/s00280-015-2836-2. Epub 2015 Aug 5.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01921140.

Keywords: Food effect; Olaparib; PARP inhibition; PK; Tablet.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Chemistry, Pharmaceutical
  • Cross-Over Studies
  • Diet, High-Fat / adverse effects
  • Drug Administration Schedule
  • Female
  • Food-Drug Interactions*
  • Half-Life
  • Humans
  • Intestinal Absorption
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Phthalazines / adverse effects
  • Phthalazines / chemistry
  • Phthalazines / pharmacokinetics*
  • Phthalazines / therapeutic use
  • Piperazines / adverse effects
  • Piperazines / chemistry
  • Piperazines / pharmacokinetics*
  • Piperazines / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects
  • Poly(ADP-ribose) Polymerase Inhibitors / chemistry
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacokinetics*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Tablets

Substances

  • Antineoplastic Agents
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Tablets
  • olaparib

Associated data

  • ClinicalTrials.gov/NCT01921140