Safety and Efficacy of Bexagliflozin Compared to Placebo as Add-on Therapy to Metformin in Type 2 Diabetes Subjects
Condition: Type2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Bexagliflozin tablets, 20 mg; Bexagliflozin tablets, placebo; Bexagliflozin tablets, 20 mg
Intervention description: Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.; Each subject will receive placebo (inactive tablet) once daily for the duration of the study.; Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.
Intervention MeSH terms: Bexagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 351.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to investigate the effect of bexagliflozin compared to placebo
      as an add-on therapy to metformin in lowering hemoglobin A1c (HbA1c) levels in subjects with
      type 2 diabetes mellitus (T2DM).
    

Eligibility criteria:

        The subjects were required to meet the following criteria at the time of enrollment to be
        eligible for the study:

          1. Had been age ≥ 20 years at screening. Women of childbearing potential were required to
             have tested negative for pregnancy and have agreed to abstinence or contraception for
             the duration of the study to avoid any possible pregnancy. Females who were surgically
             sterile (hysterectomy, oophorectomy) or postmenopausal (absence of menses greater than
             12 months) were eligible if they had tested negative for pregnancy at screening.

          2. a) Had a history of T2DM with an HbA1c level of ≥ 7.5% and ≤ 10.5% at screening, or b)
             Had a history of T2DM with an HbA1c level of >10.5% and ≤ 12.0% at screening

          3. Had been prescribed a stable dose of metformin (≥1500 mg per day in the US or ≥ 1000
             mg per day in Japan) as their sole anti-diabetic medication

          4. Had a body mass index (BMI) ≤ 45 kg m-2

          5. Had been able to comprehend and willing to provide written informed consent in
             accordance with institutional and regulatory guidelines

          6. Had no recent changes to their medications for hypertension or hyperlipidemia (if
             applicable)

          7. Had the ability to regularly self-administer medication, as evidenced by consumption
             of all, or at worst one less than all, doses of run-in medication prior to
             randomization

        Subjects who met any of the following criteria were to be excluded from the study:

          1. Had a diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young

          2. Were pregnant or breastfeeding

          3. Had one or more hemoglobin alleles that affect HbA1c measurement

          4. Had a history of genitourinary tract infection (e.g., UTI, GMI, vaginitis, balanitis)
             within 6 weeks of screening or a history of ≥ 3 genitourinary infections requiring
             treatment within 6 months of screening

          5. Had an estimated glomerular filtration rate (eGFR), as calculated by the modification
             of diet in renal disease study equation (MDRD), < 60 mL min-1 per 1.73 m2

          6. Had a sitting systolic blood pressure >180 mmHg or a sitting diastolic blood pressure
             > 110 mmHg at screening

          7. Had exposure to hypoglycemic agent(s) other than metformin during the 8 weeks prior to
             screening

          8. Had a history of illicit drug use or alcohol abuse in the past 2 years

          9. Had a life expectancy < 2 years

         10. Had a diagnosis of New York Heart Association (NYHA) Class IV heart failure within 3
             months of screening

         11. Had experienced an MI, unstable angina, stroke, or hospitalization for heart failure
             within 3 months of screening

         12. Had exposure to an investigational drug within 30 days

         13. Had a previous exposure to bexagliflozin or EGT0001474

         14. Had a history of SGLT2 inhibitor treatment

         15. Were participating in another interventional trial

         16. Were not able to comply with the study scheduled visits

         17. Had any condition, disease, disorder, or clinically relevant abnormality that, in the
             opinion of the primary investigator, would jeopardize the subject's appropriate
             participation in this study or obscure the effects of treatment

         18. Had an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 × ULN
             or total bilirubin ≥ 1.5 × ULN at screening