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372 TABLET: food effect study of niraparib tablets in patients with advanced solid tumours
  1. Debra L Richardson1,
  2. Gerald Falchook2,
  3. R Donald Harvey3,
  4. Manish Sharma4,
  5. Navid Hafez5,
  6. Erika Hamilton6,
  7. Amita Patnaik7,
  8. Sarina A Piha-Pau8,
  9. Minal Barve9,
  10. Trisha Wise-Draper10,
  11. Manish R Patel11,
  12. Afshin Dowlati12,
  13. Joseph Pascuzzo13,
  14. Shou-Ching Tang14,
  15. Christina Faltermeier15,
  16. Izabela A Malinowska16,
  17. Luda Shtessel16,
  18. Alina Striha17 and
  19. Elizabeth Potocka18
  1. 1Gynecologic Oncology, Stephenson Cancer Center/University of Oklahoma Health Sciences Center and Sarah Cannon Research Institute, Oklahoma City, Ok, United States
  2. 2Drug Development Unit, Sarah Cannon Research Institute at HealthONE, Denver, Co, United States
  3. 3Hematology and Medical Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, Ga, United States
  4. 4Medical Oncology, START Midwest, Grand Rapids, Mi, United States
  5. 5Medical Oncology, Yale Cancer Center, New Haven, Ct, United States
  6. 6Medical Oncology, Sarah Cannon Research Institute at Tennessee Oncology, Nashville, Tn, United States
  7. 7START San Antonio, San Antonio, San Antonio, Tx, United States
  8. 8Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Tx, United States
  9. 9Medical Oncology, Mary Crowley Cancer Research Center, Dallas, Tx, United States
  10. 10Medical Oncology, University of Cincinnati Cancer Center, Cincinnati, Oh, United States
  11. 11Drug Development, Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, Fl, United States
  12. 12Hematology and Oncology, University Hospitals Seidman Cancer Center and Case Western Reserve University Cleveland, Cleveland, Oh, United States
  13. 13Medical Oncology, California Cancer Associates for Research and Excellence, San Diego, Ca, United States
  14. 14Cancer Center and Research Institute, University of Mississippi Medical Center, Cancer Center and Research Institute, Jackson, Ms, United States
  15. 15Pharmacokinetics, IQVIA, Leawood, Ks, United States
  16. 16Oncology Clinical Development, GSK, Waltham, Ma, United States
  17. 17Plus-Project Partnership Ltd, Knutsford, England, UK
  18. 18Clinical Pharmacology Modeling and Simulation, GSK, Waltham, Ma, United States

Abstract

Introduction/Background Niraparib is a poly(ADP-ribose) polymerase inhibitor approved in ovarian cancer with a starting dose of 200 or 300 mg/day via 100 mg capsules and is under investigation in other solid tumours. In Stage 2 of the TABLET study, the tablet (1×300 mg) and capsule (3×100 mg) formulations were found to be bioequivalent. We report Stage 3, which assessed the impact of a high-fat meal on niraparib pharmacokinetics (PK) when given as a tablet.

Methodology This was a US, open-label, multicentre, single-crossover, randomised-sequence study. Eligible patients were ≥18 years, had histologically/cytologically confirmed advanced solid tumours (metastatic/local), disease progression despite standard therapy, and ECOG PS 0–2. In PK Period 1, patients received 1×300 mg niraparib tablet in a fasted (10-hour fast) or fed (high-fat meal) state, followed by a 7-day PK sampling and 7–11-day washout period. In PK Period 2, patients crossed over to the alternative scenario. FDA guidance for food effect (FE) studies was followed. Single-dose safety was assessed throughout. PK parameters included maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) and extrapolated to infinity (AUC0–∞). 90% confidence intervals (CIs) for fed-to-fasted-state ratios of geometric least-squares means (GLSM) were determined for each parameter; a FE was defined when 90% CIs fell outside 0.8–1.25 equivalence limits.

Results In total, 19 FE-evaluable patients were included. Niraparib Cmax, AUC0-t, and AUC0–∞ were 11%, 32% and 28% higher in the fed versus fasted state; 90% CIs of GLSM ratio fell outside predefined limits (Table). tmax was not statistically different. Inter-patient variability was greater than the observed FE magnitude; therefore, FE was not considered clinically meaningful.

Conclusion A modest FE was observed on niraparib tablet exposure. No new safety signals were reported.

Funding: GSK213362; NCT03329001.

Disclosures Please see the attached disclosures for each author.

Medical writing support was provided by Claire Kelly, PhD, at Fishawack Indicia, UK, part of Avalere Health, and funded by GSK.

Abstract 372 Table 1

Statistical analyses of PK parameters

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