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Clinical Drug Investigation

, Volume 34, Issue 11, pp 763–772 | Cite as

Bioequivalence of Saxagliptin/Metformin Extended-Release (XR) Fixed-Dose Combination Tablets and Single-Component Saxagliptin and Metformin XR Tablets in Healthy Adult Chinese Subjects

  • Anders Gummesson
  • Haiyan Li
  • Michael Gillen
  • John Xu
  • Mohammad Niazi
  • Boaz Hirshberg
Original Research Article

Abstract

Background and Objectives

As compared with individual tablets, saxagliptin/metformin extended-release (XR) fixed-dose combination (FDC) tablets offer the potential for increased patient compliance with the convenience of once daily dosing. The aim of the present study was to show that the FDC of saxagliptin and metformin XR is bioequivalent to co-administration of the individual components when given to Chinese subjects residing in China.

Methods

This was a randomized, open-label, single-dose, two-period, cross-over pharmacokinetic study in two cohorts of healthy adult Chinese male subjects (n = 32 in each cohort) under fed conditions. In cohort 1, the pharmacokinetic properties of a saxagliptin/metformin XR 5/500 mg FDC tablet were compared with those of co-administration of a 5 mg saxagliptin tablet and a 500 mg metformin XR tablet. In cohort 2, the pharmacokinetic properties of a saxagliptin/metformin XR 5/1,000 mg FDC tablet were compared with those of co-administration of a 5 mg saxagliptin tablet and 2 × 500 mg metformin XR tablets. The two cohorts were independent of each other with respect to treatment and results. The pharmacokinetic properties of the active metabolite of saxagliptin (5-hydroxy-saxagliptin), as well as the safety and tolerability of each treatment, were also evaluated.

Results

For both cohorts, saxagliptin and metformin in the FDCs were bioequivalent to the individual components, as the limits of the 90 % confidence intervals of the geometric least squares mean ratios were contained within the 80–125 % bioequivalence limits for the area under the plasma concentration–time curve parameters and within the 70–143 % bioequivalence limits for the maximum plasma concentration. Similar exposures of 5-hydroxy-saxagliptin were observed with the two treatment regimens within each cohort. Co-administration of saxagliptin and metformin XR was generally safe and well tolerated as the FDCs or as individual tablets.

Conclusion

Saxagliptin/metformin XR 5/500 mg and saxagliptin/metformin XR 5/1,000 mg FDCs were bioequivalent to individual tablets of saxagliptin and metformin XR of the same strengths and were generally well tolerated. These results in healthy Chinese subjects are consistent with those of previous assessments of saxagliptin/metformin XR FDC in the saxagliptin clinical development programme.

Keywords

Metformin Saxagliptin Acute Tonsillitis Metformin Hydrochloride Healthy Chinese Subject 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors wish to thank the staff and subjects of the Phase I Unit at Peking University Third Hospital in Beijing, China, for their contributions to these studies. The design, funding and publication support for this study was provided by AstraZeneca and the Bristol-Myers Squibb Company. All authors contributed to the conduct of the study and the data analysis/interpretation, and independently drafted, critically revised and approved the final manuscript. Haiyan Li is a current employee of Peking University Third Hospital. Anders Gummesson, Michael Gillen, John Xu, Mohammad Niazi and Boaz Hirshberg were employees of AstraZeneca at the time of this research. Editorial assistance was provided by Kevin Schofield and Janet E. Matsuura of Complete Healthcare Communications, Inc. (Chadds Ford, PA, USA) and was funded by AstraZeneca and the Bristol-Myers Squibb Company.

Ethical Standards

This study was performed in accordance with the Declaration of Helsinki and in compliance with the International Conference on Harmonisation/Good Clinical Practice and applicable regulatory requirements. The final clinical study protocol, including the information and consent forms, was approved by the Peking University Third Hospital Medical Science Research Ethics Committee before any subjects were enrolled. All subjects provided written informed consent prior to initiation of the study.

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Anders Gummesson
    • 1
  • Haiyan Li
    • 2
  • Michael Gillen
    • 3
  • John Xu
    • 3
  • Mohammad Niazi
    • 1
    • 4
  • Boaz Hirshberg
    • 3
  1. 1.AstraZeneca Global Medicines DevelopmentMölndalSweden
  2. 2.Peking University Third Hospital (PU3H)BeijingPeople’s Republic of China
  3. 3.AstraZeneca Global Medicines DevelopmentWilmingtonUSA
  4. 4.AstraZeneca Early Clinical DevelopmentMölndalSweden

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