Pharmacokinetics and bioequivalence of two formulations of mifepristone tablets in healthy Chinese subjects under fasting conditions: a single-center, open, randomized, single-dose, double-period, two-sequence, crossover trial

Objective: A bioequivalence (BE) study was performed to evaluate the pharmacokinetics, safety, and bioequivalence of two formulations of mifepristone tablets in healthy Chinese volunteers under fasting conditions.

Methods: A single-center, open, randomized, single-dose, double-period, two-sequence, crossover study in healthy subjects under fasting conditions was performed. The subjects received a single fasting dose of mifepristone (10 mg/tablet) during the first and second periods, followed by a 14-day washout period, during which frequent pharmacokinetic (PK) sampling occurred up to 120 h. The pharmacokinetic parameters of mifepristone were calculated based on the plasma drug concentration-time profile. Primary endpoints were the BE of major pharmacokinetic parameters (AUC_0-t and AUC_0-∞) and the maximum observed serum concentration (C_max). Secondary endpoints were safety parameters.

Results: Forty subjects (34 male and 6 female subjects) were randomly assigned to treatment, with 39 completing the two-period study. After the single administration of mifepristone tablets (test preparation vs. reference preparation) under fasting conditions, the geometric mean ratios (GMRs) of C_max, AUC_0-t, and AUC_0-∞ were 98.76%, 104.28%, and 104.83%, respectively. The primary metabolites of mifepristone (RU42633 and RU42698),the GMRs of C_max, AUC_0-t, AUC_0-∞ were 102.33% and 100.97%, 103.17% and 103.71%, 104.02% and 103.84%, respectively. Similarly, for another metabolite of mifepristone (RU42698), the GMRs of C_max, AUC_0-t, and AUC_0-∞ were 100.97%, 103.71%, and 103.84%, respectively. All 90% confidence intervals (CIs) for the test/reference AUC ratio and C_max ratio were within the acceptable range (80%-125%) for BE, which met the requirements of bioequivalence. No serious adverse events (AEs) occurred, and all AEs were classified as level 1 or 2.

Conclusion: The PK parameters of mifepristone and its metabolites (RU42633 and RU42698) were measured using the (GMRs) of AUC_0-t, AUC_0-∞, and C_max and were similar between the test and reference drug. The two formulations of mifepristone showed good tolerability and a similar safety profile.

Clinical trial registration: chinadrugtrials.org.cn, identifier CTR20182413.