title: Lack of a Pharmacokinetic Interaction Between Saxagliptin and Dapagliflozin in Healthy Subjects: A Randomized Crossover Study.
abstract: This single-dose, open-label, randomized, 3-period, 3-treatment crossover drug-drug interaction study was conducted to evaluate differences in the pharmacokinetic properties of saxagliptin and dapagliflozin when coadministered.
  
  
  
  Healthy subjects (N = 42) were randomized to receive saxagliptin 5 mg alone, dapagliflozin 10 mg alone, or saxagliptin 5 mg plus dapagliflozin 10 mg coadministered; there was a washout period of ≥6 days between treatments. Serial blood samples for determining saxagliptin, 5-hydroxy saxagliptin (5-OH saxagliptin; major active metabolite) and dapagliflozin plasma concentrations and pharmacokinetic parameters were collected before and up to 60 hours after the dose. No interaction was to be concluded if the 90% CIs for the geometric mean ratios of the combination compared with each drug given alone for Cmax and AUCinf were within 0.80 to 1.25.
  
  
  
  The results indicated that dapagliflozin had no effect on the pharmacokinetic properties of saxagliptin, 5-OH saxagliptin, or saxagliptin total active moiety and vice versa. The 90% CIs for Cmax and AUCinf for all comparisons were contained entirely within the 0.80 to 1.25 equivalence intervals. Other pharmacokinetic parameters (apparent oral clearance or half-life) of saxagliptin or dapagliflozin were similar when each medicine was administered alone or when coadministered. No safety profile or tolerability findings of concern were observed during the study. All adverse events were mild, and no serious adverse events were reported.
  
  
  
  These data indicate that coadministration of saxagliptin and dapagliflozin exhibits no pharmacokinetic interaction and is well tolerated. ClinicalTrials.gov identifier: NCT01662999.
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: Susan
authors.initials: S
authors.lastname: Lubin
authors.affiliation: ICON Development Solutions, LLC, Hanover, Maryland.
authors.forename: Laurie
authors.initials: L
authors.lastname: Reynolds
authors.affiliation: ICON Development Solutions, LLC, Hanover, Maryland.
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
authors.affiliation: ICON Development Solutions, LLC, Hanover, Maryland.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Marion
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Frank
authors.initials: F
authors.lastname: LaCreta
authors.affiliation: AstraZeneca, Gaithersburg, Maryland. Electronic address: david.boulton2@astrazeneca.com.
authors.forename: David W
authors.initials: DW
authors.lastname: Boulton
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004151:Dipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: C558749:5-hydroxysaxagliptin; D001559:Benzhydryl Compounds; D004151:Dipeptides; D005960:Glucosides; C529054:dapagliflozin; C502994:saxagliptin; D000218:Adamantane
keywords: dapagliflozin; dipeptidyl peptidase-4 (DPP-4) inhibitor; drug interaction; saxagliptin; sodium-glucose cotransporter 2 (SGLT-2) inhibitor