Bioequivalence study of BH009 and Winthrop (docetaxel) injection (an authorized generic drug of Taxotere) in patients with advanced solid tumor: An open-label, randomized, single-dose, two-way crossover evaluation.

Abstract

e13002 Background: Taxotere (docetaxel injection) clinically used to treat solid tumors (e.g., breast, prostate, gastric, lung, and head and neck cancer) is associated with hypersensitivity reactions attributed to its excipient, polysorbate 80. BH009 is a novel polysorbate 80-free formulation of docetaxel injection that could reduce hypersensitivity reactions associated with polysorbate 80 and preclude the need for dexamethasone premedication. Methods: This multicenter, randomized, open-label, two-way crossover study compared the pharmacokinetics and safety of BH009 and Taxotere (Winthrop (docetaxel) injection). Patients received single-dose of 75 mg/m2 BH009 or Taxotere IV over 60 min, with ≥21-day washout between doses. Primary endpoints were to evaluate pharmacokinetics and establish the bioequivalence of BH009 relative to Taxotere. Blood samples were evaluated for pharmacokinetics and bioequivalence, and safety evaluation included treatment-emergent adverse events (TEAEs) and serious adverse events. A total of 46 subjects were randomized, and 41 subjects have completed the study. Results: The ratio of geometric means for AUC0-t, AUC0-∞ and Cmax following administration of BH009 (Test product (T)) and Taxotere (Winthrop (docetaxel) injection) (Reference product (R)), were 0.99 (90% CI, 91.89% - 107.18%) , 0.98 (90% CI, 91.10% - 106.04%) and 1.00 (90% CI, 92.18% - 108.00%), respectively. Statistical analyses reveal that 90% confidence interval for geometric least square mean ratio of (T/R) is within the acceptance range of 80.00% to 125.00% for primary pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞ required for concluding bioequivalence between the test and reference product. The test and reference product were well tolerated by the patients, and the safety profile of the test product complies with the known safety profile of the reference product. A total of 198 TEAEs were reported during the course of the study. 94 TEAEs were reported after administration of Test product (T). 104 TEAEs were reported after administration of reference product (R). No serious adverse events or deaths occurred during the course of the study. Conclusions: This study established the bioequivalence of BH009 to Taxotere. BH009 is the first polysorbate 80-free formulation of docetaxel injection which is bioequivalent to Taxotere and may provide a safer alternative to Taxotere. Clinical trial information: NCT04889599 .