Bioequivalence evaluation of risedronate sodium in healthy Chinese participants under fasting conditions: a randomized, open-label, single-dose, three-period, partial replicate crossover study.

Risedronate sodium is a widely used bisphosphonate for the treatment of osteoporosis and other metabolic bone disorders. This study aimed to evaluate the bioequivalence and safety of a test formulation of risedronate sodium 35 mg tablets compared with the reference formulation in healthy Chinese participants under fasting conditions. A randomized, open-label, single-dose, three-period, partial replicate crossover study was conducted in healthy participants. Forty-five participants were enrolled and 38 completed the study. Plasma concentrations of risedronic acid were measured using a validated liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters were calculated using non-compartmental analysis. Bioequivalence was assessed using the reference-scaled average bioequivalence approach. The geometric mean values of Cmax, AUC0-t, and AUC0-∞ for the test formulation were 28.50 ng/mL, 115.40 h.ng/mL, and 129.60 h.ng/mL, respectively, compared with 26.67 ng/mL, 107.01 h.ng/mL, and 119.03 h.ng/mL for the reference formulation. The geometric mean ratios for Cmax, AUC0-t, and AUC0-∞ were 1.1077, 1.0894, and 1.0897, respectively, all within the predefined acceptance range. For the primary pharmacokinetic parameters, the point estimate of the test/reference mean ratios were within 0.80-1.25 and the upper bounds of the one-sided 95% confidence intervals for the RSABE criteria were below zero. Both formulations were generally well tolerated, and no serious adverse events were reported. These findings demonstrate that the test and reference formulations of risedronate sodium 35 mg tablets are bioequivalent under fasting conditions and exhibit comparable safety profiles. Clinical Trial Registration: CTR20201946.