Bexagliflozin Efficacy and Safety Trial

Study Overview
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Brief Summary
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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) and increased risk of cardiovascular adverse events. The data from this study will be combined with the data from other bexagliflozin studies in a meta-analysis of CV safety outcomes.

Detailed Description
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Approximately 130 investigative sites globally are planned to participate in this study. An estimated 1650 subjects with inadequately controlled T2DM and an elevated risk of cardiovascular adverse events will be randomized to bexagliflozin tablets, 20 mg, or placebo in a ratio of 2:1 in addition to the background anti-diabetic medications. The study is an event-driven trial. The treatment period will end when the last randomized subject has completed at least 52 weeks of treatment and a total of at least 134 subjects have experienced a cardiac event.

Official Title
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A Double Blind Placebo Controlled Study to Evaluate the Effects of Bexagliflozin on Hemoglobin A1c in Patients With Type 2 Diabetes and Increased Risk of Cardiovascular Adverse Events

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Bexagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a diagnosis of T2DM Subjects who have had a stable treatment regimen for T2DM for the past 3 months Subjects who present with at least one of the following 3 histories: Group 1: A history of atherosclerotic vascular disease Group 2: A history of heart failure Group 3: Age ≥ 55 years with diabetes for ≥ 10 years, uncontrolled hypertension, currently smoking, reduced kidney function, or cholesterol problems Exclusion Criteria: Diagnosis of type 1 diabetes mellitus or maturity-onset/diabetes of the young History of genitourinary tract infections Evidence of abnormal liver function History of MI, stroke or hospitalization for heart failure in the past 3 months Prior kidney transplant or evidence of kidney problems Prior or planned pace maker implantation Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bexagliflozin tablets, 20 mg<br>Each subject will receive bexagliflozin 20 mg once daily for the duration of the study. | Drug: Bexagliflozin<br>* 20 mg, tablet<br>* Other names: EGT0001474;|
| Placebo Comparator: Placebo tablets<br>Each subject will receive placebo (inactive tablet) once daily for the duration of the study. | Drug: Placebo<br>* 20 mg tablet to match active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Week 24 | The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of treatment with 20 mg bexagliflozin tablets in type 2 diabetic subjects with increased risk of cardiovascular adverse events. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Week 24 for Subjects Who Have Been Prescribed Insulin | To evaluate the effect of 20 mg bexagliflozin on the change in HbA1c from baseline to week 24 in randomized subjects who have been prescribed insulin to control their diabetes | 24 weeks | 
| Change in Body Weight From Baseline to Week 48 | To evaluate the effect of 20 mg bexagliflozin on the change in body weight from baseline to week 48 in randomized subjects with a BMI ≥ 25 kg/m2 compared to placebo | 48 weeks | 
| Change in Systolic Blood Pressure From Baseline to Week 24 in Subjects Hypertensive at Baseline | To evaluate the effect of 20 mg bexagliflozin on the change in systolic blood pressure (SBP) from baseline to week 24 in subjects with baseline systolic blood pressure ≥ 140 mmHg compared to placebo | 24 weeks |