Bioequivalence study of Combination Tablets of Saxagliptin / Dapagliflozin / Metformin XR (Extended-release) and Dapagliflozin / Metformin XR Relative to Individual Components in Healthy Subjects

Exclusion Criteria

• -Subjects will not enter the study if any of the following exclusion criteria
• are fulfilled:
• 1. History of any clinically significant disease or disorder which, in the
• opinion of the PI, may either put the volunteer at risk because of
• participation in the study, or influence the results or the volunteer's
• ability to participate in the study.
• 2. Current or recent (within 3 months of first IMP dosing)
• gastrointestinal disease that may impact drug absorption and affect the
• PK of the study drugs. Additionally, any gastrointestinal surgery (e.g.,
• partial gastrectomy, pyloroplasty) including cholecystectomy that may
• impact drug absorption.
• 3. Any major surgery, as determined by the investigator, within 4 weeks
• of first IMP dosing.
• 4. Donation of > 400 mL of blood within 8 weeks or donation of plasma
• (except at the Screening Visit) within 4 weeks of first IMP dosing.
• 5. Blood transfusion within 4 weeks of first IMP dosing.
• 6. Inability to tolerate oral medication.
• 7. Inability to tolerate venipuncture or inadequate venous access as
• determined by the investigator.
• 8. Recent (within 6 months of first IMP dosing) drug or alcohol abuse as
• defined in the Diagnostic and Statistical Manual of Mental Disorders,
• Fourth Edition (DSM-IV), Diagnostic Criteria for Drug and Alcohol Abuse.
• 9. Subjects who drink more than 3 cups of coffee or other caffeinecontaining
• products a day, or 5 cups of tea a day.
• 10. Use of tobacco-containing or nicotine-containing products (including
• but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine
• patches, nicotine lozenges, or nicotine gum) within 6 months prior to
• first check-in (Day -1, Treatment Period 1), or a positive nicotine test
• (i.e., cotinine) at Screening and/or check-in.
• 11. History of diabetes mellitus.
• 12. History of heart failure.
• 13. History of chronic or recurrent urinary tract infection (defined as 3
• occurrences per year)
• 14. Recent vulvovaginal mycotic infection (within 2 months prior to first
• IMP dosing).
• 15. Any other sound medical, psychiatric and/or social reason as
• determined by the investigator.
• 16. Any clinically significant illness, medical/surgical procedure, or
• trauma within 4 weeks of Screening.
• 17. Any positive result on screening for serum hepatitis B surface
• antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)
• antibody.
• 18. Has received another new chemical entity (defined as a compound
• which has not been approved for marketing) within 3 months of the first
• administration of IMP in this study. The period of exclusion begins 3
• months after the final dose or one month after the last visit whichever is
• the longest. Note: subjects consented and screened, but not randomized
• in this study or a previous Phase1 study, are not excluded.
• 19. History of severe allergy/hypersensitivity or ongoing
• allergy/hypersensitivity, as judged by the PI or history of
• hypersensitivity to drugs with a similar chemical structure or class to
• saxagliptin, dapagliflozin and metformin.
• 20. Positive screen for drugs of abuse or cotinine at Screening or on first
• admission to the study center or positive screen for alcohol on first
• admission to the study center
• 21. Use of saxagliptin, dapagliflozin and/or metformin within 3 months
• prior to the first administration of IMP.
• 22. Use of any prescription drugs or OTC acid controllers within 4 weeks
• prior to the first administration of IMP except medication cleared by the
• medical monitor.
• 23. Use of drugs with enzyme-inducing properties such as St John's Wort
• within 3 weeks prior to the first administration of IMP.
• 24. Use of any prescribed or non-prescribed medication including
• analgesics (other than paracetamol/acetaminophen), herbal remedies,
• megadose vitamins (intake of 20 to 600 times the recommended daily
• dose) and minerals during the 2 weeks prior to the first administration
• of IMP or longer if the medication has a long half-life. Note: Hormonal
• replacement therapy is not allowed.
• 25. Involvement of any AstraZeneca, PAREXEL or study site employee or
• their close relatives.
• 26. Vulnerable subjects, e.g., kept in detention, protected adults under
• guardianship, trusteeship, or committed to an institution by
• governmental or juridical order.