Bioequivalence of Fixed-Dose Dapagliflozin-Pioglitazone in Healthy Indian Adults: Results From the Randomized Crossover PRO-4 Study

Objective The study assessed the bioequivalence of a fixed-dose combination (FDC) of dapagliflozin 10 mg/pioglitazone 15 mg co-administered with the reference products Forxiga® 10 mg: AstraZeneca Pharmaceuticals LP, Indiana, USA and Pioglit® 15 mg: Sun Pharma Laboratories Ltd., Assam, India in healthy adult participants under fasting conditions. Materials and methods A randomized, open-label, single-dose, two-period, crossover design was used in the study. Eligible participants were randomly assigned to receive either the test FDC or the respective reference products during the first period, followed by the administration of the alternate treatment after a 7-day washout interval. The primary pharmacokinetic parameters included maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to last measurable concentration (AUC0-t), while secondary parameters were area under the curve extrapolated to infinity (AUC0-∞), time to reach maximum plasma concentration (Tmax), and elimination half-life (t½). Results Forty-two healthy male volunteers were randomized; 39 completed both study periods. For dapagliflozin, the geometric mean of the test-to-reference ratios were 94.22% for Cmax (90% CI: 86.54%-102.58%) and 98.04% for AUC0-t (90% CI: 96.01%-100.11%). For pioglitazone, the corresponding values were 102.35% for Cmax (90% CI: 88.12%-118.87%) and 107.39% for AUC0-t (90% CI: 92.97%-124.05%). All results were within the acceptable bioequivalence range of 80.00-125.00%. Two mild adverse events were observed, with no serious or clinically significant safety issues reported. Conclusion The FDC of dapagliflozin and pioglitazone was bioequivalent to the individual reference products in fasting, healthy male subjects and was well-tolerated.