A Study to Assess the Bioequivalence of Dapagliflozin/Metformin XR Fixed-dose Combination Tablets in Healthy Subjects
Condition: Bioequivalence; Fixed Dose Combination Tablets; Healthy Male and Female Subjects
Intervention: dapagliflozin/metformin XR 5/500 mg test drug (Mount Vernon); dapagliflozin/metformin XR 5/500 mg reference drug (Humacao); dapagliflozin/metformin XR 10/1000 mg test drug (Mount Vernon); dapagliflozin/metformin XR 10/1000 mg reference drug (Humacao)
Intervention description: single fixed-combination dose tablets; single fixed-dose combination tablets; single fixed-dose combination tablets; single fixed-dose combination tablets
Intervention MeSH terms: Metformin; Dapagliflozin
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: dapagliflozin/metformin XR 5/500 mg; dapagliflozin/metformin XR10/1000 mg; bioequivalence; fixed dose combination tablets; pharmacokinetic; type 2 Diabetes Mellitus (T2DM); safety

Summary:

      This is a bioequivalence study to compare 2 fixed-dose combination tablets of
      dapagliflozin/metformin XR manufactured at 2 different plants in healthy subjects under
      fasting and fed conditions
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed and dated, written informed consent prior to any study specific
             procedures

          2. Healthy male and female subjects aged 18 - 55 years with suitable veins for
             cannulation or repeated venipuncture

          3. Females must have a negative serum pregnancy test at screening and on admission to the
             unit, must not be lactating and must be of non-childbearing potential, confirmed at
             screening by fulfilling 1 of the following criteria:

               -  Post-menopausal defined as amenorrhea for at least 12 months or more following
                  cessation of all exogenous hormonal treatments and follicle-stimulating hormone
                  (FSH) levels in the post-menopausal range

               -  Documentation of irreversible surgical sterilization by hysterectomy, bilateral
                  oophorectomy or bilateral salpingectomy, but not tubal ligation

          4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50
             kg and no more than 100 kg inclusive at screening

        Exclusion Criteria:

          1. History of any clinically significant disease or disorder which, in the opinion of the
             Investigator, may either put the subject at risk because of participation in the
             study, or influence the results or the subject's ability to participate in the study

          2. History or presence of gastrointestinal, hepatic or renal disease, or any other
             condition known to interfere with absorption, distribution, metabolism, or excretion
             of drugs

          3. Any clinically significant illness, medical/surgical procedure, or trauma within 4
             weeks of the first administration of investigational medicinal product

          4. Any clinically significant abnormalities in clinical chemistry, hematology, or
             urinalysis results, as judged by the investigator

          5. Any clinically significant abnormal findings in vital signs, as judged by the
             investigator

          6. Any clinically significant abnormalities on 12-lead ECG as judged by the investigator

          7. Any positive result on screening for serum hepatitis B surface antigen (HBsAg),
             hepatitis C antibody and human immunodeficiency virus (HIV) antibody

          8. Known or suspected history of drug abuse, as judged by the investigator

          9. 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.

         10. Plasma donation within 1 month of screening or any blood donation/loss more than 500
             mL during the 3 months prior to screening

         11. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as
             judged by the investigator or history of hypersensitivity to drugs with a similar
             chemical structure or class to dapagliflozin/metformin XR.

         12. Current smokers or those who have smoked or used nicotine products within the 3 months
             prior to screening

         13. Positive screen for drugs of abuse, cotinine or alcohol at screening or on each
             admission to the study center

         14. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks
             prior to the first administration of IMP

         15. Use of any prescribed or non-prescribed medication including antacids, analgesics
             (other than paracetamol/acetaminophen), herbal remedies, vitamins and minerals during
             the 2 weeks prior to the first administration of IMP or longer if the medication has a
             long half-life

         16. Known or suspected history of alcohol abuse or excessive intake of alcohol as judged
             by the investigator

         17. Involvement of any AstraZeneca or study site employee or their close relatives

         18. Judgment by the investigator that the subject should not participate in the study if
             they have any ongoing or recent (i.e., during the screening period) minor medical
             complaints that may interfere with the interpretation of study data or are considered
             unlikely to comply with study procedures, restrictions and requirements

         19. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship,
             trusteeship, or committed to an institution by governmental or juridical order