Bioequivalence Study Coadministered to Healthy Subjects in the Fasted State
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Saxagliptin; Dapagliflozin
Intervention MeSH terms: Dapagliflozin; Saxagliptin
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 19 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to demonstrate bioequivalence of coadministered drugs on healthy
      subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed Informed Consent Form

               -  Signed written informed consent must be obtained from the subjects in accordance
                  with requirements of the study center's IRB or IEC before the initiation of any
                  protocol-required procedures.

          2. Target Population

               -  Healthy subjects as determined by no clinically significant deviation from normal
                  in medical history, psychiatric history, physical examination findings, vital
                  sign measurements, 12-lead ECG measurements, physical measurements, and clinical
                  laboratory test results.

          3. Age and Reproductive Status

               -  Males and females, ages 19 to 55 years, inclusive. To extent possible, the
                  distribution of men and women between the sequences will be balanced

               -  Women of childbearing potential (WOCBP) must have a negative serum or urine
                  pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24
                  hours prior to the start of study drug.

               -  Women must not be breastfeeding. d) WOCBP must agree to follow instructions for
                  method(s) of contraception for the duration of treatment with study drugs
                  saxagliptin and dapagliflozin plus 5 half lives of study drug dapagliflozin (the
                  longer half life between the 2 drugs; 3 days) for a total of 3 days following
                  treatment completion.

                  e) Men who are sexually active with WOCBP must agree to follow instructions for
                  method(s) of contraception for the duration of treatment with study drugs
                  saxagliptin and dapagliflozin plus 5 half lives of dapagliflozin (the longer half
                  life between the 2 drugs; 3 days) for a total of 3 days following treatment
                  completion.

                  f) Azoospermic males and WOCBP who are continuously not heterosexually active are
                  exempt from contraceptive requirements. However, they must still undergo
                  pregnancy testing as described in this section

             Exclusion Criteria:

               -  Any significant acute or chronic medical illness.

               -  Current or recent (within 3 months of study drug administration) gastrointestinal
                  disease that could impact upon the absorption of study drug

               -  Any other sound medical, psychiatric, and/or social reason as determined by the
                  investigator

               -  Any major surgery within 4 weeks of study drug administration.

               -  Any prior GI surgery including cholecystectomy (remote history of appendectomy
                  will not be exclusionary).

               -  Current, recent (within 3 months of study drug administration), or remote history
                  of pancreatitis.

               -  Donation of blood or plasma to a blood bank or in a clinical study (except at
                  screening visit) within 4 weeks before study drug administration.

               -  Blood transfusion within 4 weeks of study drug administration. h) Inability to
                  tolerate oral medication.

               -  Inability to be venipunctured performed and/or tolerate venous access.

               -  Use of tobacco- or nicotine-containing products (including, but not limited to,
                  cigarettes, pipes, e-cigarettes, cigars, chewing tobacco, nicotine patches,
                  nicotine lozenges, or nicotine gum) within 6 months before check-in.

               -  Drug or alcohol abuse (within 2 years of study drug administration) as defined in
                  the Diagnostic and Statistical Manual of Mental Disorders - 4th Edition,
                  Diagnostic Criteria for Drug and Alcohol Abuse History of glucose intolerance or
                  diabetes mellitus.

               -  For females, history of chronic or recurrent urinary tract infection (UTI)
                  (defined as 3 occurrences per year) or UTI in the past 3 months. For males, any
                  UTI within the previous 5 years that has not been thoroughly evaluated and for
                  which an explanation is not clear.

               -  History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal
                  mycotic infections.

               -  Any other sound medical, psychiatric, and/or social reason as determined by the
                  investigator.

             Physical and Laboratory Test Findings

               1. Evidence of organ dysfunction or any clinically significant deviation from normal
                  in physical examination, vital signs, ECGs, or clinical laboratory determinations
                  beyond what is consistent with the target population.

               2. Abnormal urinalysis at screening (may repeat once). If the urinalysis is abnormal
                  on Day -1 of Period 1, continuation in the study is up to the investigator's
                  discretion. The CRO medical monitor should be consulted.

               3. Glucosuria or hematoria at screening or Day -1 of Period 1, repeat is not
                  permitted. d) A positive nicotine test (ie, cotinine).

             e) Abnormal liver function tests (alanine or aspartate aminotransferase [ALT or AST,
             respectively], or total bilirubin).

             f) Any of the following on 12-lead ECG prior to study drug administration, confirmed
             by repeat.

             i) PR ≥ 210 ms ii) QRS ≥ 120 ms iii) QT ≥ 500 ms iv) QTcF ≥ 450 ms g) Positive urine
             screen for drugs of abuse. h) Positive urine alcohol test. i) Positive blood screen
             for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human
             immunodeficiency virus (HIV)-1 or HIV-2 antibodies at screening.

          4. Allergies and Adverse Drug Reaction

               1. History of allergy or adverse reactions to DPP4 or SGLT inhibitors or related
                  compounds.

               2. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).

          5. Other Exclusion Criteria

               1. Prisoners or subjects who are involuntarily incarcerated.

               2. Subjects who are compulsorily detained for treatment of either a psychiatric or
                  physical (eg, infectious disease) illness.

               3. Inability to comply with restrictions and prohibited activities/treatments