Bioequivalence study of a fixed-dose combination of Dapagliflozin/ Vildagliptin Sustained Release tablets in healthy adult male subjects: A Randomized, Open-Label, Crossover Study
A fixed-dose combination (FDC) of Dapagliflozin and Vildagliptin sustained release (SR) was developed, and its bioequivalence with coadministration of the individual tablets was evaluated in an open-label, randomized, two-treatment, two sequences, two-period, cross-over single-dose study. The study's primary objective was to compare and assess the rate and extent of absorption of Dapagliflozin 10 mg /Vildagliptin SR 100 mg FDC with individual drugs. Twenty-four healthy subjects were randomized, and 23 completed the study. For both Dapagliflozin and Vildagliptin SR, the 90% confidence intervals (CIs) for the ratio (Test product: Reference product) of geometric means of peak plasma concentration (Cmax), the area under the curve from 0 hours to the last measurable concentration (AUC0-t), and AUC-time curve up to infinity (AUC0-∞), were within acceptance criteria for bioequivalence, i.e., 80% to 125%. Overall, both reference and test products were safe and well tolerated.
Keywords: Bioequivalence, Dapagliflozin, Fixed-dose combination, Pharmacokinetic, Sustained release, Vildagliptin, Type 2 diabetes
2. Chadha M, Das AK, Deb P, Gangopadhyay KK, Joshi S, Kesavadev J, Kovil R, Kumar S, Misra A, Mohan V. Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting. Diabetes Ther. 2022 May; 13(5):1097-1114. https://doi.org/10.1007/s13300-022-01219-x
3. Vakkalagadda B, Vetter ML, Rana J, Smith CH, Huang J, Karkas J, Boulton DW, LaCreta F. Bioequivalence of saxagliptin/Dapagliflozin fixed-dose combination tablets compared with coadministration of the individual tablets to healthy subjects. Pharmacol Res Perspect. 2016 Jan 12; 3(6):e00201. https://doi.org/10.1002/prp2.201
4. Ahrén B. Vildagliptin: a DPP-4 inhibitor for the treatment of Type 2 diabetes. Diabetes Management. 2012 Sep 1; 2(5):453. https://doi.org/10.2217/dmt.12.40
6. Dhillon S. Dapagliflozin: A Review in Type 2 Diabetes. Drugs. 2019 Jul; 79(10):1135-1146. https://doi.org/10.1007/s40265-019-01148-3
8. Fioretto P, Giaccari A, Sesti G. Efficacy and safety of Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in diabetes mellitus. Cardiovasc Diabetol. 2015 Oct 17; 14:142. https://doi.org/10.1186/s12933-015-0297-x
9. Profit L, Chrisp P, Nadin C. Vildagliptin: the evidence for its place in the treatment of type 2 diabetes mellitus. Core Evid. 2008 Jun; 3(1):13-30.
10. Min SH, Yoon JH, Moon SJ, Hahn S, Cho YM. Combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes: a systematic review with meta-analysis. Sci Rep. 2018 Mar 13; 8(1):4466. https://doi.org/10.1038/s41598-018-22658-2
11. Kalra S, Bhattacharya S. Bioequivalence study of two different dapagliflozin tablet formulations in healthy adult Indian volunteers. Journal of Diabetology. 2022 Jul 1; 13(3):235
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