Bexagliflozin Drug/Drug Interaction Study With Exenatide Injection
Condition: Type2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Bexagliflozin; Exenatide Injection
Intervention description: Bexagliflozin tablets, 20 mg; Byetta® (Exenatide), 10 ug, bid, subcutaneous injection
Intervention MeSH terms: Exenatide; Bexagliflozin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to examine the drug-drug interaction when given the study drug,
      bexagliflozin, with one of the most commonly prescribed glucagon-like peptide 1 receptor
      agonist (GLP-1 RA) exenatide. The study will also evaluate how safe the study drug is and how
      well the study drug is tolerated when administered with exenatide injection.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects who were between the ages of 18 and 65 years, inclusive, in
             good health based on medical history, physical examination, electrocardiogram and
             routine laboratory tests.

          2. Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2, inclusive.

          3. Subjects who were non-smokers for at least 3 months prior to screening.

          4. Subjects with adequate venous access at multiple sites in both arms.

          5. Subjects who were willing and able to be confined to the clinical research facility as
             required by the protocol.

          6. Subjects who had the ability to comprehend and who were willing to provide written
             informed consent in accordance with institutional and regulatory guidelines.

        Exclusion Criteria:

          1. Subjects who were determined by the investigator or sub-investigator to be unsuitable
             for participation in the study based on medical conditions or factors that would have
             influenced adherence to study activities.

          2. Subjects with a clinically significant history of allergy to drugs or latex.

          3. Subjects with a history of hypoglycemia.

          4. Subjects with a history of alcohol or drug dependence in the last 12 months.

          5. Subjects who donated 400 mL of whole blood within 56 days, 200 mL of whole blood
             within one month, or donated blood components within 14 days of screening.

          6. Subjects who used prescription or over-the-counter (OTC) drugs within 14 days prior to
             the first dose.

          7. Subjects who used vitamin preparations or supplements (including St. John's Wort and
             ginseng) within 14 days prior to the first dose .

          8. Subjects who were not willing to refrain from smoking, alcohol, grapefruit, grapefruit
             juice or related products, caffeine consumption (including chocolate), and strenuous
             exercise within 72 h prior to Day 1 and through the end of the PK study.

          9. Male subjects who did not agree to refrain from donating sperm and use appropriate
             birth control methods including condoms with spermicide, female partner's use of
             diaphragm with spermicide, or stable oral, implanted, or injected contraceptive
             hormones, or with an intrauterine device, or female partner is surgically sterile
             (i.e. have undergone partial or full hysterectomy, or bilateral oophorectomy) or
             postmenopausal (absence of menses greater than 12 months and age >45 years), for a
             period of 30 days after discharge from the clinic.

         10. Female subjects of childbearing potential who were not willing to use an adequate
             method of contraception including bilateral tubal ligation, intrauterine device,
             diaphragm with spermicide and male partner's use of male condom with spermicide, and
             to not become pregnant for the duration of the study. Female subjects who were
             surgically sterile (partial or full hysterectomy, or bilateral oophorectomy) or
             postmenopausal (absence of menses greater than 12 months and age >45 years) were
             eligible if they tested negative on the pregnancy test.

         11. Subjects who had been treated with an investigational drug within 30 days or 7
             half-lives of the investigational drug, whichever is longer, prior to the first dose
             of study drug in this trial.

         12. Subjects who had previously received exenatide, or any other GLP-1 RAs within three
             months from the screening or subjects who had had any GLP-1 RA and suffered an adverse
             reaction due to the medication.

         13. Subjects who had previously received bexagliflozin, or any other SGLT2 inhibitors
             within 3 months from the screening.

         14. Subjects whose screening ECG demonstrates any one of the following: heart rate >100
             bpm, QRS >120 msec, QTc >470 msec (corrected by Fridericia's formula), PR >220 msec (a
             subject with PR >220 msec was generally to be excluded but exceptions may have been
             allowed at the discretion of the investigator), or any clinically significant
             arrhythmia.

         15. Subjects whose sitting blood pressure was above 140/90 mmHg at screening. If the
             sitting blood pressure at screening was above 140/90 mmHg, one repeat measurement was
             allowed and the subject may have been randomized if the blood pressure was 140/90 +/-5
             mm Hg at the discretion of the Investigator.

         16. Subjects who had a positive result of hepatitis B surface antigen (HBsAg), hepatitis C
             virus (HCV) antibody, urinary drug or urinary cotinine test.

         17. Subjects with human immunodeficiency virus (HIV) infection.

         18. Subjects who had had a febrile illness within 5 days prior to the first dose of study
             medication.

         19. Subjects vaccinated within 30 days (with the exception of the flu vaccine) prior to
             the first dose of investigational drug.

         20. Subjects with a history of acute or chronic pancreatitis or gall stones.

         21. Positive urine glucose at screening.

         22. Subjects with estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 or a
             history of kidney transplant.

         23. Subjects with digestion problems, including gastroesophageal reflux disease, irritable
             bowel syndrome, gastroparesis, and any other disorder deemed by the investigator to be
             clinically significant.