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

Purpose: 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 C max , AUC 0-t, and AUC0-infinity 0-infinity 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 C max , AUC0-t,and 0-t, and AUC0-infinity 0-infinity were 94.82-108.97%, 92.94-104.28%, and 92.81-103.85%, respectively, and pivotal fed C max , AUC0-t, 0-t , and AUC0-infinity 0-infinity were 82.78-100.97%, 91.59-104.67%, and 92.17-104.76%, respectively. The 90% confidence interval of the two preparations, C max , AUC0-t, 0-t , and AUC0-infinity, 0-infinity , 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.