Bioequivalence Comparison of Two Formulations of Fixed-Dose Combination Glimepiride/Metformin (2/500 mg)Tablets in Healthy Volunteers

Abstract

Glimepiride/metformin(2/500mg) is an oral antihyperglycemic agent for the treatment of type 2 diabetes. A generic glimepiride/metformin(2/500mg) fixed-dose combination(FDC) tablet was developed recently. This study was designed to collect data for submission to Korean regulatory authorities to allow the marketing of the test formulation. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy male adult volunteers. This single-dose, randomized, double-blind, two-way crossover trial was conducted at Bestian Medical Center in Bucheon, Korea. In total, 40male Korean volunteers were enrolled. The subjects were randomized to receive an FDC tablet containing the glimepiride/metformin(2/500mg) test or reference formulation, and pharmacokinetic (PK) parameters were measured. After a 1-week washout period, the other formulation was administered and the PK parameters were measured again. The Cmax and AUC∞ were determined from blood samples obtained at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, and 24h after drug administration. Bioequivalence was considered established if the 90%CIs of the geometric mean ratios(GMRs) of the test-to-reference formulations for Cmax and AUC∞ were within the predetermined regulatory range of 80-125%. In total, 40 healthy male subjects were enrolled and completed the study(mean[SD]age, 23.2[2.26]years[range, 19-30years]; weight, 68.95[8.30]kg[range, 52.0-87.0kg]; and height, 175.4[5.34]cm[range, 164-189cm]). The GMRs(90% CI) of the glimepiride Cmax and AUC∞ were 1.006 (0.947-1.069) and 1.010 (0.953-1.071), respectively. For metformin, the values were 1.019 (0.959-1.083) and 1.035 (0.989-1.084), respectively. The two formulations had similar PK parameters. The test formulation of glimepiride/metformin(2/500mg) FDC tablets met the Korean regulatory criteria for bioequivalence.