Bioequivalence Comparison of Two Formulations of Fixed Dose Combination Sitagliptin/Metformin (50/1000 mg) Immediate Release (IR) Tablets in Fed Condition

Background: This study aimed to evaluate the bioequivalence of the Fixed-Dose Combination (FDC) sitagliptin 50 mg/metformin 1000 mg tablets compared to Janumet® (sitagliptin 50 mg/metformin 1000 mg tablets) in healthy male volunteers under fed conditions.

Methods: This was a randomized, single-dose, open-label, two-period, twosequence, crossover and single-dose study to compare the Bioequivalence (BE) profile of two FDC of sitagliptin 50 mg/metformin 1000 mg Immediate Release (IR) in 26 adult healthy subjects. The Pharmacokinetic (PK) parameters C_max and AUC_0-t were calculated based on the plasma drug concentration-time profile measured by Liquid Chromatography-Mass Spectrometry (LC-MS/MS). The safety was assessed throughout the study. Bioequivalence was evaluated using 90% Confidence Intervals (CIs) for the ratio test/reference of log Area Under the Concentration- Time Curve (AUC) from time 0 to the last quantifiable concentration and log peak concentration. The two formulations Test (T) and Reference (R) were considered bioequivalent if 90% Confidence Interval (CI) were within BE acceptance range of 80.00%-125.00% for C_max and AUC_0-t.

Results: All 26 subjects completed both study periods. The 90% Confidence Intervals (CIs) of the test/reference ratio were C_max: 110.46% (103.26%-118.15%) and AUC_0-t 104.82% (99.81%-110.08%) of sitagliptin and C_max: 99.85% (93.61%- 106.52%) AUC_0-t: 102.51 (96.57%-108.82%) to metformin. PK parameters were within the accepted bioequivalence criteria. The results show that no significant differences were observed between the pharmacokinetic profiles of the T and R formulations. No serious adverse events were reported in this study.

Conclusion: The two formulations of sitagliptin 50 mg/metformin 1000 mg IR (FDC) were bioequivalent in healthy subjects under fed conditions. The geometric mean ratio and 90% CI for primary PK parameters, C_max and AUC_0-t, of T and R formulation were within the range 80% to 125%.

Author(s): Evelyn Pena

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