Pharmacokinetics and bioequivalence of rasagiline mesylate tablets in healthy Chinese subjects under fasting and fed conditions: an open, randomized, single-dose, four-period crossover clinical trial

This clinical trial evaluated the pharmacokinetic profiles and bioequivalence of a generic rasagiline mesylate tablet versus the branded reference product in healthy Chinese subjects under fasting and fed conditions to support an abbreviated new drug application. Safety and tolerability were monitored throughout the study. We conducted a single-center, randomized, open-label, four-period, two-sequence crossover trial in healthy Chinese participants. In each period, subjects received a single 1 mg oral dose of either formulation; plasma rasagiline concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were derived by non‑compartmental analysis. Bioequivalence was assessed using either the reference-scaled average bioequivalence (RSABE) or the standard average bioequivalence (ABE), depending on the within‑subject standard deviation (S WR ) of the reference formulation. A total of 64 subjects were enrolled and randomized (30 fasting, 34 fed). For peak plasma concentrations (C max ), which exhibited high variability (S WR > 0.294), RSABE was used, while ABE was applied for AUC 0−t and AUC 0−∞ . Under fasting conditions, the geometric mean ratio (GMR) of test/reference for C max was 109.80%; under fed conditions, it was 111.60%. The 95% upper confidence bounds for both conditions were less than zero. The 90% confidence intervals for AUC 0−t and AUC 0−∞ GMRs were 98.82%-107.11% and 98.96%-107.11% (fasting), and 96.92%-102.34% and 97.15%-102.64% (fed), all falling within the 80–125% acceptance range. No serious adverse events were reported. The test formulation met the bioequivalence criteria under both prandial states and was well tolerated, with a safety profile similar to that of the reference product. The trial was first registered at chinadrugtrials.org.cn (CTR20230947, date: March 29, 2023) and subsequently retrospectively registered at chictr.org.cn (ChiCTR 2500099491, March 25, 2025).