A Dose Range Finding Study to Evaluate the Effect of Bexagliflozin Tablets in Subjects With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Bexagliflozin tablets; Bexagliflozin tablets, placebo
Intervention description: Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.; Bexagliflozin tablets, placebo, are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.
Intervention MeSH terms: Bexagliflozin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 292.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      The purpose of this study was to investigate the effect of bexagliflozin in lowering
      hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). Bexagliflozin
      is an orally administered drug for the treatment of T2DM and is classified as a Sodium
      Glucose co-Transporter 2 (SGLT2) Inhibitor. This study was to enroll both treatment naive and
      those subjects previously treated with one oral hypoglycemic agent (OHA). Approximately 320
      subjects eligible for randomization was to receive bexagliflozin tablets, 5, 10, 20 mg or
      placebo, once daily for 12 weeks in an outpatient setting.
    

Eligibility criteria:

        The following subjects were eligible for randomization:

          1. men or women ≥ 20 years of age at screening. Women of childbearing potential must test
             negative by urine pregnancy test.

          2. were treatment naïve or taking one oral anti-diabetic medication in combination with
             diet and exercise

          3. were diagnosed with T2DM with HbA1c levels at screening between 7.0% and 8.5%
             (inclusive) if treatment naïve or with HbA1c levels between 6.5 and 8.5% (inclusive)
             if on one oral anti-diabetic medication

          4. had a body mass index (BMI) ≤ 40 kg/m2

          5. were taking stable doses of medication for hypertension or hyperlipidemia that has not
             changed for at least 30 days prior to screening (if applicable)

          6. were able to comprehend the study participation requirements and willing to provide
             written informed consent in accordance with institutional and regulatory guidelines

          7. were able to maintain adequate glycemic control at the run-in visit (for subjects who
             complete the washout)

          8. had an HbA1c between 7.0 and 8.5% (inclusive) prior to randomization (day -3 to -5)

          9. were capable of adhering to the investigational product administration requirements as
             evidenced by omission of no more than one dose of run-in medication

        Subjects who exhibited any of the following characteristics were to be ineligible for
        randomization:

          1. Diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young

          2. Used parenteral therapy for treatment of diabetes

          3. Pregnancy or current breastfeeding status

          4. Hemoglobinopathy or carrier status for hemoglobin alleles that affect HbA1c
             measurement

          5. Genitourinary tract infection within 6 weeks of screening or history of ≥3
             genitourinary infections requiring treatment within 6 months of screening

          6. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at screening.

          7. Uncontrolled hypertension at screening

          8. A positive result on hepatitis B surface antigen, hepatitis C, or positive result from
             screen for drugs of abuse

          9. History of human immunodeficiency virus infection

         10. Life expectancy < 2 years

         11. History of New York Heart Association Class 4 heart failure within 3 months of
             screening

         12. History of myocardial infarction, unstable angina, stroke, or hospitalization for
             heart failure within 3 months of screening

         13. History of treatment with an investigational drug within 30 days or within 7 half
             lives of the investigational drug, whichever is longer

         14. Previous treatment with bexagliflozin

         15. Had taken or within 6 months of taking any Sodium Glucose Transporter 2 (SGLT2)
             inhibitors prior to screening

         16. Participation of another interventional trial

         17. Not able to comply with the study scheduled visits

         18. Affected by any condition, disease, disorder, or clinically relevant abnormality that,
             in the opinion of the investigator, would jeopardize the subject's appropriate
             participation in this study.

         19. Liver function tests resulting in Alanine transaminase (ALT) or aspartate transaminase
             (AST) ≥ 2.5 x upper limit of normal (ULN) or total bilirubin ≥ 1.5 x ULN, with the
             exception of isolated Gilbert's syndrome ,at screening

         20. Exhibited fasting plasma glucose ≥ 250 mg/dL (13.9 mmol/L) on two or more consecutive
             days prior to randomization or exhibited 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

         21. Fasting Plasma Glucose ≥ 250 mg/dL at randomization

         22. Prior renal transplantation or evidence of nephrotic syndrome, defined as a urine
             albumin-to-creatinine ratio (UACR) > 2000 mg/g at screening