Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Bexagliflozin; Placebo
Intervention description: Bexagliflozin tablet, 20 mg; Placebo (inactive) tablet to match the active comparator
Intervention MeSH terms: Bexagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 312.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      This was a phase 3, multi-center, randomized, double-blind, placebo-controlled,
      parallel-group study to evaluate the efficacy and safety of oral administration of
      bexagliflozin at 20 mg versus placebo in subjects with T2DM, moderate renal impairment and
      inadequate glycemic control.
    

Eligibility criteria:

        Each subject was required to meet the following criteria at the time of enrollment to be
        eligible for the study:

          1. To have been male or non-pregnant female ≥ 20 years of age. Women of childbearing
             potential were required to agree to use contraception throughout the study to avoid
             any possible pregnancy. Females who were surgically sterile (hysterectomy,
             oophorectomy) or postmenopausal (absence of menses for greater than 12 months and age
             > 45 years) were eligible if they tested negative on the urine pregnancy test.

          2. To have had a diagnosis of T2DM with an HbA1c between 7.0 and 10.5% (inclusive) at the
             time of screening.

          3. To have been treatment naïve or to have been treated with a stable regimen of
             anti-diabetic medications. At the time of screening, the doses and frequency of all
             anti-diabetic medications were to have been stable for 8 weeks.

          4. To have had an eGFR ≥ 30 and < 60 mL min-1 per 1.73 m2 at 2 time points: screening
             (V1), and 1 additional time point between 1 and 12 months of screening (may be
             obtained from available medical records). The eGFR was calculated by the MDRD
             equation.

          5. To have had a body mass index (BMI) ≤ 45 kg per m2 (inclusive).

          6. To have been taking stable doses of medications for hypertension or hyperlipidemia (if
             applicable) for at least 30 days prior to randomization

          7. To have had stable eGFR between the historic value and day of screening (no more than
             20% change in eGFR between the most recent historical value and the value determined
             at the screening visit V1).

        9.3.2 Exclusion Criteria

        Potential participants who exhibited any of the following characteristics were excluded
        from the study:

          1. A diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young (MODY)

          2. A hemoglobinopathy that could affect HbA1c measurement

          3. Frequent symptomatic hypoglycemia (greater than one episode per week on average)

          4. A history of genitourinary tract infection within 6 weeks of screening or history of ≥
             3 genitourinary infections requiring treatment within the last 6 months

          5. A cancer, active or in remission for < 3 years (Non-melanoma skin cancer or basal cell
             carcinoma or carcinoma in situ of the cervix were not grounds for exclusion)

          6. A history of alcohol or illicit drug abuse in the past 2 years

          7. Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase >
             1.5 × upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome);
             or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULN

          8. A history of MI, stroke or hospitalization for heart failure, or hospitalization for
             unstable angina in the prior 3 months

          9. Evidence of NYHA class IV heart failure at screening or randomization

         10. A history of taking an SGLT2 inhibitor within 3 months of screening

         11. Any condition, disease, disorder, or clinically relevant laboratory abnormality that,
             in the opinion of the PI, would jeopardize the subject's appropriate participation in
             this study or obscure the effects of treatment

         12. A current status of pregnancy or breastfeeding

         13. A current status of renal replacement therapy (peritoneal or hemodialysis) or a
             history of renal transplantation

         14. A corrected serum calcium < 8 mg dL-1 at screening (V1) or randomization (V3)

         15. Uncontrolled hypertension (systolic blood pressure >170 mm Hg or diastolic blood
             pressure >110 mm Hg)

         16. Participation in another interventional trial or exposure to an investigational drug
             within 30 days or 7 half-lives of screening, whichever was longer

         17. Previous exposure to bexagliflozin or EGT0001474

         18. Evidence of having skipped dosing more than once during the run-in period

         19. A fasting blood glucose value during the run-in period ≥ 250 mg dL-1 (13.9 mmol L-1)
             associated with severe clinical signs or symptoms of hyperglycemia

         20. Any episode of symptomatic hypoglycemia during the run-in period in which symptoms
             were severe

         21. An inability to comprehend or unwillingness to provide written informed consent in
             accordance with institutional and regulatory guidelines