title: Bioequivalence of saxagliptin/dapagliflozin fixed-dose combination tablets compared with coadministration of the individual tablets to healthy subjects.
abstract: Saxagliptin and dapagliflozin are individually indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The bioequivalence of saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg fixed-dose combination (FDC) tablets compared with coadministration of the individual tablets and the food effect on both strengths of saxagliptin/dapagliflozin FDCs were evaluated in this open-label, randomized, single-dose crossover study. Healthy subjects were randomized to saxagliptin 2.5 mg + dapagliflozin 5 mg fasted, 2.5/5 mg FDC fasted, 2.5/5 mg FDC fed (Cohort 1) or saxagliptin 5 mg + dapagliflozin 10 mg fasted, 5/10 mg FDC fasted, 5/10 mg FDC fed (Cohort 2). Serial blood samples for pharmacokinetics of saxagliptin and dapagliflozin were obtained predose and up to 60 h postdose. Bioequivalence of FDC tablets versus individual components was concluded if the 90% CIs for FDC to individual component geometric mean ratios of C max, AUC 0-T, and AUC inf of both analytes were between 0.80 and 1.25. Seventy-two subjects were randomized; 71 (98.6%) completed the study. Saxagliptin/dapagliflozin 2.5/5 mg and 5/10 mg FDC tablets were bioequivalent to the individual tablets administered concomitantly. Food had no clinically meaningful effect on saxagliptin or dapagliflozin overall systemic exposure. Saxagliptin/dapagliflozin FDC tablets were bioequivalent to coadministration of the individual components in healthy subjects under fasted conditions and food had no clinically meaningful effect on bioavailability.
authors.affiliation: Bristol-Myers Squibb Princeton New Jersey.
authors.forename: Blisse
authors.initials: B
authors.lastname: Vakkalagadda
authors.affiliation: Bristol-Myers Squibb Princeton New Jersey.
authors.forename: Marion L
authors.initials: ML
authors.lastname: Vetter
authors.affiliation: Bristol-Myers Squibb Princeton New Jersey.
authors.forename: Jignasa
authors.initials: J
authors.lastname: Rana
authors.affiliation: PPD Wilmington North Carolina.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Smith
authors.affiliation: PPD Wilmington North Carolina.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Bristol-Myers Squibb Princeton New Jersey.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Karkas
authors.affiliation: AstraZeneca Gaithersburg Maryland.
authors.forename: David W
authors.initials: DW
authors.lastname: Boulton
authors.affiliation: Bristol-Myers Squibb Princeton New Jersey.
authors.forename: Frank
authors.initials: F
authors.lastname: LaCreta
keywords: Bioequivalence; dapagliflozin; dipeptidyl peptidase‐4 inhibitor; fixed‐dose combination; saxagliptin; sodium‐glucose cotransporter 2 inhibitor