Pharmacokinetic and Pharmacodynamics Study of Multiple Oral Doses of Vildagliptin Sustained Release 100 Mg Tablets under the Fed State in Healthy Volunteers
This study evaluated the pharmacokinetic and pharmacodynamic profile of the vildagliptin 100 mg sustained release (SR) administered once daily compared to vildagliptin 50 mg immediate release (IR) administered twice daily in healthy, adult human subjects under fed conditions.
This was a randomized, balanced, open-label, two-treatment, two-period, two-sequence, crossover multiple oral dose study in healthy adult subjects under fed conditions. The subjects were randomized to receive either a test product, i.e., vildagliptin SR 100 mg once daily, or a reference product, i.e., vildagliptin 50 mg twice daily. The duration of the study was 25 days. The primary pharmacokinetic parameter evaluated was the area under the concentration-time curve for one dosing interval at steady-state (AUC0-τ, ss). Bioequivalence was determined by assessing whether the 90% confidence intervals (CIs) for the geometric mean ratio of test to reference drug fell within predefined margins of 80% −125% for AUC0-τ, ss. The pharmacodynamics parameters evaluated were percent dipeptidyl-peptidase-4 (DPP-4) inhibition and weighted average percent DPP-4 inhibition.
Forty healthy adult males completed the study. There was no significant difference between the pharmacokinetic and pharmacodynamic profiles in reference and test products. The mean ± standard deviation (SD) values of AUC0-τ, ss for test and reference product was 2689.06 ± 835.47 2875.57 ± 703.85 ng. hr/mL, respectively. The 90% CIs of geometric least-square means of test/reference ratio for AUC0-τ, ss with vildagliptin SR 100 mg tablet was 86.32-97.26% within the bioequivalence acceptance range. The test and reference product showed over 90% inhibition of DPP-4 activity with multiple doses. The weighted average percent of DPP-4 inhibition (0-24 hrs) was 92.66% with the test product and 93.26% with the reference product. Both products were well tolerated during the entire study period. No serious or life-threatening adverse events (AEs) were reported during the study.
The two formulations of vildagliptin, i.e., vildagliptin SR 100 mg once daily and vildagliptin 50 mg twice daily, demonstrated similar pharmacokinetic and pharmacodynamic profiles under fed conditions in healthy adult males. Both formulations were bioequivalent and well tolerated.
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