Treatment A (Reference) Treatment B (Test) Test/Reference STUDY 1 Parameter 100 mg CANA + 2 X 500 mg MET IR (n=58) 2 X (50 mg CANA/500 mg MET)IR FDC (n=58) Estimated Ratio, % (90% CI) (Test/Ref.) Cmax (ng/mL) 722.50 679.01 93.98(86.10-102.58) AUClast 8523.60 8561.16 100.44(98.27-102.66) AUC∞ (ng.h/mL)a 8815.54 8808.21 99.92(97.68-102.20) tmax(h) 3.00 (0.98 – 12.00)b 3.00 (1.00 – 16.00)c   t1/2 (h) 13.7 (2.75)d 13.7 (2.84)e   STUDY 2 Parameter 100 mg CANA + 2 X 850 mg MET IR (n=62) 2 X (50 mg CANA/850 mg MET) IR FDC (n=62) Estimated Ratio, % (90% CI) (Test/Ref.) Cmax (ng/mL) 705.28 740.96 105.06 (97.89 - 112.76) AUClast 8370.97 8487.99 101.40 (99.73 – 103.10) AUC∞ (ng.h/mL) 8632.52 8748.88 101.35 (99.62 – 103.10) tmax(h) 3.52 (1.00-10.00)f 3.00 (1.00-10.00)g   t1/2 (h) 14.4 (3.14)f 14.5 (2.89)g   STUDY 3 Parameter 100 mg CANA + 2 X 1000 mg MET IR (n=57) 2 X (50 mg CANA/1000 mg MET) IR FDC (n=57) Estimated Ratio, % (90% CI) (Test/Ref.) Cmax (ng/mL) 803.00 775.90 96.62(89.12-104.77) AUClast 8609.25 8752.70 101.67(99.33-104.06) AUC∞ (ng.h/mL)a 8904.71 9078.94 101.96(99.57-104.40) tmax(h) 4.00 (1.00-10.00) 3.00 (1.00-10.00)h   t1/2 (h) 13.92 (2.96)i 14.47 (3.45)c   STUDY 4 Parameter 300 mg CANA + 2 X 500 mg MET IR (n=60) 2 X (150 mg CANA/500 mg MET) IR FDC (n=60) Estimated Ratio, % (90% CI) Cmax (ng/mL) 2558.49 2673.78 104.51 (98.47-110.92) AUClast 27679.43 28125.42 101.61 (99.94-103.31) AUC∞ (ng.h/mL)c 28262.76 28707.97 101.58 (99.84-103.34) tmax(h) 4.00 (1.00-12.00)j 3.00 (1.50-10.03)b   t1/2 (h) 13.9 (2.49)j 14.1 (2.79)d   STUDY 5 Parameter 300 mg CANA + 2 X 850 mg MET IR (n=61) 2 X (150 mg CANA/850 mg MET) IR FDC (n=61) Estimated Ratio, % (90% CI) (Test/Ref.) Cmax (ng/mL) 2527.63 2606.24 103.11(95.91 – 110.86) AUClast 30037.82 30344.32 101.02(99.60 – 102.47) AUC∞ (ng.h/mL)h 30852.23 31148.41 100.96(99.44 – 102.50) tmax(h) 3.00 (1.50-12.02)b 3.00 (1.00-12.00)d   t1/2 (h) 14.80 (3.08)d 14.89 (3.45)d   STUDY 6 Parameter 300 mg CANA + 2 X 1000 mg MET IR (n=62) 2 X (150 mg CANA/1000 mg MET) IR FDC (n=62) Estimated Ratio, % (90% CI) (Test/Ref.) Cmax (ng/mL) 2099.09 2225.02 106.00(97.90-114.77) AUClast 26960.48 27560.10 102.22(100.00-104.50) AUC∞ (ng.h/mL)j 27561.67 28234.55 102.44(100.21-104.72) tmax(h) 4.00 (0.98-24.00)g 3.00 (0.98-16.00)g   t1/2 (h) 14.29 (2.68)k 14.47 (2.88)k   Note: metformin IR tablets supplied as Glucophage® IR tablets.an=55; bn=63; cn=59; dn=62; en=57; fn=66; gn=68; hn=60; in=56; jn=61; kn=67; AUClast, area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration; AUC∞, area under the plasma concentration-time curve from time 0 to infinite time; CI: confidence interval; Cmax, maximum observed plasma concentration; n: total number of participants; Ref=reference; t1/2 (h), terminal elimination half-time and represented by arithmetic mean (SD); tmax (h), time to reach the maximum plasma concentration and reported as median (range).

Table 3: Summary statistics for geometric means and ratio of geometric means with corresponding 90% confidence intervals for canagliflozin pharmacokinetic parameters following administration of 2 IR FDC tablets (50 or 100 mg canagliflozin/500, 850, or 1,000 mg metformin) compared to coadministration of individual IR canagliflozin (100 or 300 mg) and 2 metformin (500, 850, and 1,000 mg) tablets at equivalent doses.

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