title: Bioequivalence of saxagliptin/metformin immediate release (IR) fixed-dose combination tablets and single-component saxagliptin and metformin IR tablets in healthy adult subjects.
abstract: BACKGROUND
  As compared with individual tablets, saxagliptin/metformin immediate release (IR) fixed-dose combination (FDC) tablets offer the potential for increased convenience, compliance, and adherence for patients requiring combination therapy.
  
  
  OBJECTIVE
  Two bioequivalence studies assessed the fed-state and the fasted-state bioequivalence of saxagliptin/metformin IR 2.5 mg/500 mg FDC (study 1) and saxagliptin/metformin IR 2.5 mg/1,000 mg FDC (study 2) relative to the same dosage strengths of the individual component tablets [saxagliptin (Onglyza™) and metformin IR (Glucophage(®))] administered concurrently.
  
  
  METHODS
  These were randomized, open-label, single-dose, four-period, four-treatment, crossover studies in healthy subjects (n = 24 in each study). The treatments in study 1 were a saxagliptin/metformin IR 2.5 mg/500 mg FDC tablet in the fed and fasted states on separate occasions, and saxagliptin 2.5 mg and metformin IR 500 mg tablets co-administered in the fed state and fasted states on separate occasions. The treatments in study 2 were a saxagliptin/metformin IR 2.5 mg/1,000 mg FDC tablet in the fed and fasted states on separate occasions, and saxagliptin 2.5 mg and metformin IR 1,000 mg co-administered in the fed state and fasted states on separate occasions. The pharmacokinetics, safety, and tolerability of each treatment were evaluated.
  
  
  RESULTS
  For both studies, saxagliptin and metformin in the FDCs were bioequivalent to the individual components in both the fed and the fasted states as the limits of the 90 % confidence interval of the ratio of adjusted geometric means for all key pharmacokinetic parameters were contained within the predefined 0.800 to 1.250 bioequivalence criteria. Co-administration of saxagliptin and metformin IR was generally safe and well tolerated as the FDCs or as individual tablets.
  
  
  CONCLUSIONS
  Saxagliptin/metformin IR 2.5 mg/500 mg and saxagliptin/metformin IR 2.5 mg/1,000 mg FDCs were bioequivalent to individual tablets of saxagliptin and metformin of the same strengths in both the fed and the fasted states. No unexpected safety findings were observed with saxagliptin/metformin IR administration. The tolerability of the FDC of saxagliptin/metformin IR was comparable to that of the co-administered individual components. These results indicate that the safety and efficacy profile of co-administration of saxagliptin and metformin can be extended to the saxagliptin/metformin IR FDC tablets.
authors.affiliation: Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb Company (BMS), Princeton, NJ 08543, USA.
authors.forename: Vijay V
authors.initials: VV
authors.lastname: Upreti
authors.forename: Chi-Fung
authors.initials: CF
authors.lastname: Keung
authors.forename: David W
authors.initials: DW
authors.lastname: Boulton
authors.forename: Ming
authors.initials: M
authors.lastname: Chang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Angela
authors.initials: A
authors.lastname: Tang
authors.forename: Bonnie C
authors.initials: BC
authors.lastname: Hsiang
authors.forename: Donette
authors.initials: D
authors.lastname: Quamina-Edghill
authors.forename: Ernst U
authors.initials: EU
authors.lastname: Frevert
authors.forename: Frank P
authors.initials: FP
authors.lastname: Lacreta
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004151:Dipeptides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005215:Fasting / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009515:New Jersey; D019518:Postprandial Period; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D013607:Tablets; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane
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