Evaluation of Olaparib Tablet Safety and Pharmacokinetics in Healthy Chinese Male Subjects

Ruihua Dong,1,* Jingcheng Chen,1,* Nini Guo,2 Yingying Yang,2 Jingxuan Wu,1 Xiaoru Wang,2 Yuqin Song,1 Xueyuan Zhang2 1Phase I Clinical Trial Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Department, CSPC Zhongqi Pharmaceutical Technology (SJZ) Co., LTD., Shijiazhuang, Hebei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueyuan Zhang, Clinical Department, CSPC Zhongqi Pharmaceutical Technology (SJZ) Co., LTD., Shijiazhuang, Hebei Province, 050035, People’s Republic of China, Tel +86-311-69085585, Email [email protected]: To evaluate the safety and pharmacokinetics of olaparib tablet test formulation (T) and reference formulation (R) in healthy Chinese male subjects.Subjects and Methods: This was a single-dose, randomized-sequence, two-way crossover study including three parts: part A: a safety exploration design in lower dose (n = 14, 100 mg), part B: a pivotal comparative pharmacokinetic (PK) trial under fast condition (n = 44, 150 mg) and part C: a pivotal comparative PK trial under food condition (n = 44, 150 mg). Blood samples were collected for 72 hours and the PK parameters of Cmax, AUC0-t, and AUC0-∞ were used to evaluate PK differences.Results: PK analysis of the two olaparib formulations showed that the Geometric Least Squares Mean (GLSM) ratio 90% confidence intervals for pivotal fasting Cmax, AUC0-t, and AUC0-∞ were 94.82– 108.97%, 92.94– 104.28%, and 92.81– 103.85%, respectively, and pivotal fed Cmax, AUC0-t, and AUC0-∞ were 82.78– 100.97%, 91.59– 104.67%, and 92.17– 104.76%, respectively. The 90% confidence interval of the two preparations, Cmax, AUC0-t, and AUC0-∞, all fall within the equivalent range of 80– 125%. Both olaparib tablet formulations were well tolerated, with no serious adverse events (SAE) or adverse events (AE) causing withdrawal occurred.Conclusion: Two types of olaparib tablets were bioequivalent under both fasting and fed condition, and were generally well tolerated in healthy Chinese male subjects.Keywords: olaparib, safety, pharmacokinetics, bioequivalence, healthy Chinese male subjects