Ruth Plummer1, Helen Swaisland2, Karin Leunen3, Carla M L van Herpen4, Guy Jerusalem5, Jacques De Grève6, Martijn P Lolkema7, Patricia Soetekouw8, Morten Mau-Sørensen9, Dorte Nielsen10, James Spicer11, Anitra Fielding12, Karen So12, Wendy Bannister13, L Rhoda Molife14. 1. Northern Centre for Cancer Care, Newcastle upon Tyne, UK. ruth.plummer@ncl.ac.uk. 2. Therakin Consulting, Sandbach, UK. 3. UZ Leuven, Leuven, Belgium. 4. Radboud University Medical Center, Nijmegen, The Netherlands. 5. CHU Sart-Tilman, Liege, Belgium. 6. Universitair Ziekenhuis Brussel, Brussels, Belgium. 7. University Medical Center Utrecht, Utrecht, The Netherlands. 8. Maastricht University Medical Center, Maastricht, The Netherlands. 9. Rigshospitalet, Copenhagen, Denmark. 10. Herlev Hospital, Herlev, Denmark. 11. King's College London at Guy's Hospital, London, UK. 12. AstraZeneca, Macclesfield, UK. 13. PHASTAR, London, UK. 14. Drug Development Unit, The Royal Marsden/Institute of Cancer Research, Sutton, UK.
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 enteredPart 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.
RCT Entities:
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.
Authors: Cody J Peer; Jung-Min Lee; Jeffrey Roth; Louis Rodgers; Jeffers Nguyen; Christina M Annunziata; Lori Minasian; Elise C Kohn; William D Figg Journal: Cancer Chemother Pharmacol Date: 2017-06-02 Impact factor: 3.333
Authors: Jung-Min Lee; Ashley Cimino-Mathews; Cody J Peer; Alexandra Zimmer; Stanley Lipkowitz; Christina M Annunziata; Liang Cao; Maria I Harrell; Elizabeth M Swisher; Nicole Houston; Dana-Adriana Botesteanu; Janis M Taube; Elizabeth Thompson; Aleksandra Ogurtsova; Haiying Xu; Jeffers Nguyen; Tony W Ho; William D Figg; Elise C Kohn Journal: J Clin Oncol Date: 2017-05-04 Impact factor: 44.544
Authors: Jung-Min Lee; Cody J Peer; Minshu Yu; Lauren Amable; Nicolas Gordon; Christina M Annunziata; Nicole Houston; Andrew K L Goey; Tristan M Sissung; Bernard Parker; Lori Minasian; Victoria L Chiou; Robert F Murphy; Brigitte C Widemann; William D Figg; Elise C Kohn Journal: Clin Cancer Res Date: 2016-09-23 Impact factor: 12.531