Phase I Pharmacokinetic Study of Niraparib in Chinese Patients with Epithelial Ovarian Cancer

[摘要] Background. This randomized, open-label, single-arm, phase I study was designed to investigate the pharmacokinetics (PK) and safety of niraparib in Chinese patients with epithelial ovarian cancer. Methods. Eligible patients were randomized in a 1:1:1 ratio to receive 100, 200, or 300 mg of niraparib once daily. PK parameters were analyzed after single and multiple dose administrations. Results. Thirty-six Chinese patients were enrolled in total. Niraparib was rapidly absorbed after administration, and median time-to-peak (Tmax) was 3 hours. The long terminal elimination half-life (T1/2~35 hours) supports once-daily dosing regimen. The exposure to niraparib showed linear and dose-proportional pharmacokinetics, whereas other PK parameters such as Tmax, T1/2, and accumulation ratio were dose independent. Population PK analysis indicated that there was no effect of race on niraparib PK parameters, whereas baseline body weight had a modest impact on niraparib exposure. Grade 3/4 treatmentemergent adverse events (TEAEs; reported in ≥10% of patients) included platelet count decreased (a total of five patients who were all from the 300-mg group) and neutrophil count decreased. The TEAEs were manageable after dose modification. Conclusion. The PK profile of niraparib in Chinese patients is consistent with that in white patients. Niraparib is safe and well tolerated in Chinese patients with ovarian cancer.

[学科分类] 地质学