Study to Evaluate Effects of Probenecid, Rifampin and Verapamil on Bexagliflozin in Healthy Subjects
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Bexagliflozin; Probenecid; Rifampin; Verapamil
Intervention description: Bexagliflozin 20 mg, tablet; qd; Probenecid tablets, 500 mg; bid; Rifampin, 600 mg (2 x 300 mg capsules); qd; Verapamil hydrochloride tablet, 120 mg; qd
Intervention MeSH terms: Bexagliflozin; Rifampin; Probenecid; Verapamil
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 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 three commonly prescribed medications, probenecid, verapamil or rifampin.
      The study is to evaluate how safe the study drug is and how well the study drug is tolerated
      when taken with probenecid, verapamil or rifampin.
    

Eligibility criteria:

        Subjects meeting the following Criteria were included::

          1. Between 18 and 55 years of age at screening, inclusive, and in good health based on
             medical history, physical examination, electrocardiogram and routine laboratory tests.

          2. Had a body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2 at screening, inclusive.

          3. Abstained from tobacco consumption for at least 3 months prior to screening.

          4. Had adequate venous access at multiple sites in both arms.

          5. Willing and able to be confined to the clinical research facility as required by the
             protocol.

          6. Able to comprehend the explanation of the informed consent and willing to provide
             written informed consent in accordance with institutional and regulatory guidelines.

        Subjects who met any of the following criteria were excluded from the study:

          1. A clinically significant history of allergy to drugs or latex (at the Investigator's
             discretion.)

          2. A history of alcohol or drug dependence in the last 12 months.

          3. A history of donation of 400 mL of whole blood within two months, 200 mL of whole
             blood within one month, or blood components within 14 days prior to the first dose.

          4. A history of prescription or over-the-counter (OTC) drug use within 14 days prior to
             the first dose.

          5. A history of vitamin preparation or supplement use (including St. John's Wort and
             ginseng) within 14 days prior to the first dose.

          6. A history of strenuous physical activity within 72 hours prior to dosing.

          7. A history of exposure to an investigational drug within 30 days or 7 half-lives of the
             investigational drug, whichever was longer, prior to the first dose of investigational
             drug in this trial.

          8. A history of prior exposure to EGT0001474 or bexagliflozin at any time, or of exposure
             to any other SGLT2 inhibitors within 3 months from screening or of participation in
             previous bexagliflozin clinical trials.

          9. A history of consumption of probenecid, rifampin, or verapamil within 3 months of
             screening.

         10. A screening ECG that demonstrated any one of the following: heart rate >100 bpm, QRS
             >120 msec, QTc >470 msec (corrected by Bazett'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.

         11. A sitting blood pressure that was above 140/90 mmHg at screening. If the sitting blood
             pressure at screening was above 140/90 mmHg, one repeat measurement could have been
             taken. Subjects were to be excluded if the repeated sitting blood pressure was above
             140/90 mmHg, but exceptions may have been allowed at the discretion of the
             Investigator.

         12. A positive result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV)
             antibody, or for urinary drug or cotinine tests.

         13. A history of human immunodeficiency virus (HIV) infection.

         14. A history of febrile illness within 5 days prior to the first dose of investigational
             drug.

         15. A history of vaccination (with the exception of the flu vaccine) within 30 days prior
             to the first dose of investigational drug.

         16. An estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2 or a history of
             kidney transplant.

         17. If male, who was not surgically sterile, unwilling to refrain from donating sperm,
             and/or unwilling to use appropriate birth control when engaging in sexual intercourse
             for a period of 30 days after discharge from the clinic.

         18. Female subjects who were surgically sterile (i.e., have undergone partial or full
             hysterectomy, or bilateral oophorectomy) or postmenopausal were eligible if they
             tested negative on a urine pregnancy test.

         19. Evidence of anemia if selected for probenecid study.

         20. Evidence of abnormal liver function tests (total bilirubin >1.5 x upper limit of
             normal [ULN]); or alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
             >2.5 x ULN.

         21. If selected for the rifampin study, unwilling to refrain from the use of soft contact
             lenses during the study.

         22. Unwilling to forgo consumption of alcohol 72 hours pre admission and throughout the
             study.

         23. Unwilling to forgo consumption of grapefruit and grapefruit products from 7 days prior
             to dosing through discharge from the clinic.

         24. A history of recurrent yeast or urinary tract infections or any such infections in the
             6 months prior to first dose.

         25. A history of gout, glucose-6-phosphate dehydrogenase deficiency, or nephrolithiasis if
             a candidate for the probenecid study.