Safety and Efficacy of Bexagliflozin as Monotherapy in Patients With Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Bexagliflozin; Placebo
Intervention description: tablets containing 20 mg bexagliflozin; tablets matching the appearance of bexagliflozin tablets
Intervention MeSH terms: Bexagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 210.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to investigate the effect of bexagliflozin in lowering
      hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM).
    

Eligibility criteria:

        The study population included:

          1. Male or female adult subjects ≥ 18 years of age at screening

          2. Subjects who were treatment naïve or receiving 1 OHA in combination with diet and
             exercise

          3. Subjects with a diagnosis of T2DM

          4. Subjects with HbA1c levels at screening between 7.0% and 10.5% (inclusive) if
             treatment-naïve or with HbA1c levels between 6.5 and 10.0% (inclusive) if on 1 oral
             anti diabetic agent

          5. Subjects with a BMI ≤ 45 kg/m2

          6. Subjects whose doses of medications for hypertension or hyperlipidemia (if applicable)
             had not changed for at least 30 days prior to screening

          7. Subjects who were willing and able to return for all clinic visits and to complete all
             study required procedures

          8. Female subjects of childbearing potential who were willing to use an adequate method
             of contraception and not become pregnant for the duration of the study.

          9. Subjects who maintained glycemic control throughout washout, if applicable.

         10. Subjects who had HbA1c levels between 7.0 and 10.5% prior to randomization

         11. Subjects who had been compliant in investigational product administration by missing
             no more than 1 dose of run-in medication

        Subjects who met any of the following criteria were excluded from the study:

          1. A diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young

          2. Use of injected therapy for treatment of diabetes (insulin or GLP-1 receptor agonist
             therapy) or thiazolidinedione class drugs at the time of screening

          3. Female subjects who were pregnant or breastfeeding

          4. Hemoglobinopathy or carrier status for hemoglobin alleles that affected HbA1c
             measurement

          5. Genitourinary tract infection (e.g., UTI, GMI, vaginitis, balanitis) within 6 weeks of
             screening or history of ≥ 3 genitourinary infections requiring treatment within 6
             months from screening

          6. Estimated glomerular filtration rate (eGFR), as calculated by the modification of diet
             in renal disease study equation (MDRD), < 60 mL/min/1.73 m2 at screening

          7. Uncontrolled hypertension defined as a sitting systolic blood pressure >160 mm Hg or
             diastolic blood pressure > 95 mm Hg at screening

          8. A positive result for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV)

          9. History of alcohol or illicit drug abuse in the past 2 years

         10. Known human immunodeficiency virus (HIV) positive based on medical history

         11. Life expectancy < 2 years

         12. New York Heart Association (NYHA) Class IV heart failure within 3 months of screening

         13. MI, unstable angina, stroke, or hospitalization for heart failure within 3 months of
             screening

         14. Treatment with an investigational drug within 30 days or within 7 half-lives of the
             investigational drug, whichever was longer

         15. Previous treatment with bexagliflozin or EGT0001474

         16. Use of any SGLT2 inhibitors, either at the time of screening or in the prior 3 months

         17. Currently participating in another interventional trial

         18. Not able to comply with the study scheduled visits

         19. 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

         20. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 x ULN or
             total bilirubin ≥ 1.5 x upper limit of normal (ULN) with the exception of isolated
             Gilbert's syndrome at screening

         21. Two or more consecutive FPG measures ≥ 250 mg/dL (13.9 mmol/L) prior to randomization
             or severe clinical signs or symptoms of hyperglycemia during the washout or run-in
             periods, including weight loss, blurred vision, increased thirst, or increased
             urination, or fatigue

         22. At last visit prior to randomization, FPG level ≥ 250 mg/dL

         23. Prior renal transplantation or evidence of nephrotic syndrome (defined as a urine
             albumin-to-creatinine ratio (UACR) > 2000 mg/g at screening).