Bexagliflozin Efficacy and Safety Trial (BEST)

• ClinicalTrials.gov Identifier: NCT02558296
• Recruitment Status: Completed
• First Posted: September 23, 2015
• Results First Posted: July 7, 2021
• Last Update Posted: July 14, 2021
• Sponsor: Theracos
• Information provided by (Responsible Party): Theracos

Tracking Information

• First Submitted Date: September 22, 2015
• First Posted Date: September 23, 2015
• Results First Submitted Date: May 4, 2021
• Results First Posted Date: July 7, 2021
• Last Update Posted Date: July 14, 2021
• Actual Study Start Date: October 2015
• Actual Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 15, 2021)

Change in HbA1c From Baseline to Week 24 [ Time Frame: 24 weeks ]

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.

Original Primary Outcome Measures (submitted: September 22, 2015)

Change in HbA1c from baseline to week 24 [ Time Frame: 24 weeks ]

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.

Current Secondary Outcome Measures (submitted: June 15, 2021)

• Change From Baseline in HbA1c at Week 24 for Subjects Who Have Been Prescribed Insulin [ Time Frame: 24 weeks ]
  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
• Change in Body Weight From Baseline to Week 48 [ Time Frame: 48 weeks ]
  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
• Change in Systolic Blood Pressure From Baseline to Week 24 in Subjects Hypertensive at Baseline [ Time Frame: 24 weeks ]
  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

Original Secondary Outcome Measures (submitted: September 22, 2015)

• Change in body weight from baseline to week 48 [ Time Frame: 48 weeks ]
  To evaluate the effect of 20 mg bexagliflozin on the change in body weight from baseline to week 48in randomized subjects with a BMI ≥ 25 kg/m2 compared to placebo
• Change in systolic blood pressure from baseline to week 24 [ Time Frame: 24 weeks ]
  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

Current Other Pre-specified Outcome Measures (submitted: July 13, 2021)

• Change in HbA1c From Baseline Over Time [ Time Frame: Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168 ]
  To assess the effect of 20 mg bexagliflozin treatment on the change in HbA1c from baseline versus placebo over time up to 168 weeks
• Change in Fasting Plasma Glucose Over Time [ Time Frame: Baseline (week 0) and weeks 6, 12, 24, 36, 48, 72, 96, 120, 144 and 168 ]
  To evaluate the effect of bexagliflozin treatment on the change in fasting plasma glucose (FPG) versus placebo over time up to 168 weeks
• Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification [ Time Frame: 24 week ]
  To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period
• Proportion of Subjects Requiring an Intensification of Hypoglycemic Agent and Time to First Intensification [ Time Frame: Duration of study (168 weeks) ]
  To measure the proportion of subjects requiring an intensification of hypoglycemic agent in the bexagliflozin arm versus placebo during the entire study period
• Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent [ Time Frame: 24 weeks ]
  To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during 24 week period
• Proportion of Subjects Requiring a Relaxation of Hypoglycemic Agent [ Time Frame: Duration of study (168 weeks) ]
  To measure the proportion of subjects requiring a relaxation of hypoglycemic agent in the bexagliflozin arm versus placebo during the entire study
• Proportion of Participants With Incidence of Hospitalization for Heart Failure [ Time Frame: Duration of study (168 weeks) ]
  To measure the incidence of hospitalization for heart failure among all subjects and among subjects who have a history of heart failure at baseline

Original Other Pre-specified Outcome Measures (submitted: September 22, 2015)

• Change in HbA1c over time [ Time Frame: Duration of study ]
  To assess the effect of 20 mg bexagliflozin treatment on the change in HbA1c versus placebo over time
• Change in fasting plasma glucose over time [ Time Frame: Duration of study ]
  To evaluate the effect of bexagliflozin treatment on the change in fasting plasma glucose (FPG) versus placebo over time
• Proportion of subjects requiring an intensification of anti-diabetic regimen over time [ Time Frame: Duration of study ]
  To measure the proportion of subjects requiring an intensification of anti-diabetic regimen versus placebo over time
• Proportion of subjects requiring a relaxation of their anti-diabetic regimen over time [ Time Frame: Duration of study ]
  To measure the proportion of subjects requiring a relaxation of their anti-diabetic regimen versus placebo over time
• Incidence of hospitalization for heart failure [ Time Frame: Duration of study ]
  To measure the incidence of hospitalization for heart failure among all subjects and among subjects who have a history of heart failure at baseline
• Evaluation of the safety of exposure to bexagliflozin for a minimum of 52 weeks [ Time Frame: At least 52 weeks ]
  An additional safety objective will be to evaluate the safety of exposure to bexagliflozin for a minimum of 52 weeks in a treatment population that is at elevated risk for major adverse cardiovascular events.
• Bexagliflozin plasma concentration over time for population pharmacokinetics study [ Time Frame: 12 weeks ]
  As part of an additional pharmacokinetic study, measurement of bexagliflozin plasma concentration as a function of time from dosing (sparsely sampled) will be conducted at 30 sites and will include approximately 240 subjects.

Descriptive Information

• Brief Title: Bexagliflozin Efficacy and Safety Trial
• Official Title: 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

Brief 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) 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Type 2 Diabetes Mellitus

Intervention

• Drug: Bexagliflozin
  20 mg, tablet
  Other Names:

  • EGT0001442
  • EGT0001474
• Drug: Placebo
  20 mg tablet to match active comparator

Study Arms

• Active Comparator: Bexagliflozin tablets, 20 mg
  Each subject will receive bexagliflozin 20 mg once daily for the duration of the study.
  Intervention: Drug: Bexagliflozin
• Placebo Comparator: Placebo tablets
  Each subject will receive placebo (inactive tablet) once daily for the duration of the study.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 4, 2019): 1700
• Original Estimated Enrollment (submitted: September 22, 2015): 1650
• Actual Study Completion Date: October 23, 2019
• Actual Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Denmark, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Taiwan, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02558296
• Other Study ID Numbers: THR-1442-C-476
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Theracos
• Original Responsible Party: Same as current
• Current Study Sponsor: Theracos
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: J. Paul Lock, MD; Theracos

• PRS Account: Theracos
• Verification Date: July 2021