372 TABLET: food effect study of niraparib tablets in patients with advanced solid tumours

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.