Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax^® 70 mg tablet.
Materials and methods: A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg). Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reference-scaled average bioequivalence (RSABE) methods.
Results: The average maximum concentrations (C _max) of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC_0–t ) were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h·ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (s_WR ) for C _max and AUC_0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for C _max and AUC_0–t , respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for C _max and AUC_0–t were 90.35%–129.04% and 85.31%–117.15%, respectively, which were within the limits of the EMA for the bioequivalence of 69.84%–143.19% and 80.00%–125.00%.
Conclusion: The generic product was bioequivalent to the reference product in terms of the rate and extent of alendronate absorption after a single 70 mg oral dose under fasting conditions.
Keywords: alendronate sodium, pharmacokinetics, highly variable drug, reference-scaled average bioequivalence