The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer.

ABSTRACT

PURPOSE: Niraparib is a highly selective inhibitor of PARP-1 and PARP-2 approved in the United States for maintenance treatment of adult patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. In this open-label crossover study, we evaluated the effects of food on niraparib pharmacokinetics (PK) and safety. METHODS: Patients received a single 300-mg dose of niraparib either after a high-fat meal or under fasting conditions. After a 7-day PK assessment, all patients received a second 300-mg dose of niraparib under the opposite condition, followed by 7-day PK assessment. Blood samples for PK analyses were collected at baseline (on days 1 and 8) and up to 168 h post-dose. Bioequivalence between conditions was defined by the 90% confidence intervals (CIs) for area under the plasma concentration-time curve (AUC) from 0 to last measurable concentration (AUC0-last) and from 0 to infinity (AUC0-∞) being within the 80-125% range. RESULTS: The high-fat meal/fasting ratios of geometric least-squares means for AUC0-last and AUC0-∞ were 106.8 (90% CI 97.8-116.6) and 110.1 (90% CI 99.7-121.6), respectively, indicating bioequivalence between conditions. Mean half-life, maximum plasma concentration (Cmax), and time to Cmax after the high-fat meal were similar to, 27% smaller than, and 128% greater than after fasting, respectively. Adverse events were similar between conditions. CONCLUSIONS: A high-fat meal did not impact the PK profile of niraparib, indicating that niraparib can be taken with or without food. Niraparib was safe and well-tolerated.