Bioequivalence of a Single Dose of Two Palbociclib Formulations in Healthy Chinese Subjects Under Fasting Conditions: A Two-Period Crossover Study with Rabeprazole Pre-treatment

Wanjun Bai¹Shuo Shi^1,2Deliang Yin³Caihui Guo¹Haojing Song¹Yiting Hu¹Jin Gao¹Bo Qiu¹Xueyuan Zhang⁴Lusha Bi⁵Huizhen Wu^1*Zhanjun Dong^1*

• ¹Hebei General Hospital Affiliated to Hebei Medicine University, Shijiazhuang, China
• ²Hebei Medical University, Shijiazhuang, China
• ³Beijing Kangchuanglian Biopharmaceutical Technology Research Co Ltd, Beijing, China
• ⁴Shanghai Innovstone Therapeutics Limited, Shanghai, China
• ⁵CSPC Ouyi Pharmaceutical Co., Shijiazhuang, China

Objectives: This study assessed the pharmacokinetics, safety, and bioequivalence of generic and original palbociclib tablets in healthy Chinese subjects under fasting conditions with rabeprazole pretreatment. Methods: This was a single-dose, randomized, open-label, two-period crossover bioequivalence study conducted under fasting conditions with rabeprazole pre-treatment. In each trial, healthy Chinese subjects received 40 mg oral rabeprazole enteric-coated tablets once daily before breakfast for six days. Following an overnight fast of at least 10 hours, they took the seventh dose of rabeprazole and maintained fasting. They then received a single 125 mg oral dose of either the test or reference palbociclib tablet, followed by a 14-day washout interval between periods. Blood samples were collected from 0 to 96 hours post-dose in each period, and palbociclib plasma concentrations were determined using a validated method. The primary pharmacokinetic parameters were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals were acquired for bioequivalence analysis. The safety of both formulations was also evaluated. Results: The 90% confidence intervals for the primary pharmacokinetic parameters of Cmax (84.53-91.72%), AUC0-t (87.81-92.49%), and AUC0-∞(87.59-92.03%) all fell within the 80.00-125.00% bioequivalence range. No serious adverse events occurred during the study. This is a provisional file, not the final typeset article Conclusion: The trial confirmed that the pharmacokinetic parameters of the generic and original palbociclib tablets were bioequivalent in healthy Chinese subjects under fasting conditions with rabeprazole pre-treatment. Both formulations were safe and well tolerated. Clinical Trial Registration: The study was registered on the Drug Clinical Trial Registration and Information Disclosure Platform [http://www.chinadrugtrials.org.cn] (number: CTR20232617, date: August 23, 2023) and retrospectively registered on the Chinese Clinical Trial Registry [https://www.chictr.org.cn] (number: ChiCTR2400084355, date: May 15, 2024).