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.

In this study, a total of 48 healthy subjects were enrolled and assigned to one of three groups of 16 subjects. Each group participated in an open-label, non-randomized, fixed-sequence studies to assess potential interaction of bexagliflozin tablets, 20 mg with probenecid, rifampin or verapamil.

Sequence 1: Bexagliflozin/probenecid Sixteen healthy subjects were dosed with bexagliflozin, qd and/or probenecid tablets, 500 mg, bid, in sequential order as follows: on Day 1 subjects took bexagliflozin; on Days 3 and 4 subjects took probenecid, bid; on Day 5 subjects took one bexagliflozin, and probenecid, bid; and on Day 6 subjects took probenecid tablets, 500 mg, bid.

Sequence 2: Bexagliflozin/rifampin Sixteen healthy subjects were dosed with bexagliflozin, qd and/or 600 mg of rifampin daily in sequential order as follows: on Day 1 subjects took one bexagliflozin tablet; on Days 3 to 5, subjects took rifampin once daily; on Day 6 subjects took one bexagliflozin tablet and rifampin; and on Day 7 subjects took rifampin.

Sequence 3: Bexagliflozin/verapamil Sixteen healthy subjects were dosed with bexagliflozin, and/or verapamil tablets, 120 mg in sequential order as follows: on Day 1 subjects took one bexagliflozin tablet, on Day 4 subjects took one verapamil tablet, 1 hour before taking a bexagliflozin tablet.

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.

The adverse event data were collected from Day 0 up to Day 7 for study 1, Day 0 up to Day 8 for study 2 and Day 0 up to Day 6 for study 3 after drug administration