Safety and Efficacy of Bexagliflozin Compared to Glimepiride as Add-on Therapy to Metformin in Type 2 Diabetes Subjects

• ClinicalTrials.gov Identifier: NCT02769481
• Recruitment Status: Completed
• First Posted: May 11, 2016
• Results First Posted: May 27, 2021
• Last Update Posted: May 27, 2021
• Sponsor: Theracos
• Information provided by (Responsible Party): Theracos

Tracking Information

• First Submitted Date: May 3, 2016
• First Posted Date: May 11, 2016
• Results First Submitted Date: March 25, 2021
• Results First Posted Date: May 27, 2021
• Last Update Posted Date: May 27, 2021
• Actual Study Start Date: August 15, 2016
• Actual Primary Completion Date: June 14, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2021)

Change From Baseline in HbA1c at Week 60 [ Time Frame: Baseline and Week 60 ]

The primary objective is to demonstrate that bexagliflozin is non-inferior to glimepiride by evaluating the treatment effect on HbA1c reduction at week 60 in subjects whose T2DM is inadequately controlled by metformin. The least square mean (LSM) change from baseline to Week 60 was analyzed using a mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA).

• Original Primary Outcome Measures (submitted: May 9, 2016): Change in HbA1c from baseline to week 60 [ Time Frame: Baseline and 60 weeks ]

Current Secondary Outcome Measures (submitted: May 25, 2021)

• Change From Baseline in Body Weight at Week 60 for Subjects With Baseline BMI ≥ 25 kg/m2 [ Time Frame: Baseline and 60 weeks ]
  Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of body weight in subjects with baseline BMI ≥ 25 kg/m2 at week 60 is analyzed using ANCOVA.
• Change From Baseline in Systolic Blood Pressure (SBP) at Week 60 for Subjects With Baseline SBP ≥ 140 mmHg [ Time Frame: Baseline and 60 weeks ]
  Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of SBP in subjects with baseline SBP ≥ 140 mmHg at week 60 is analyzed using ANCOVA.
• Difference in Proportion of Subjects With ≥ 1 Severe or Documented Symptomatic Hypoglycemia Events Over 96 Weeks [ Time Frame: During the 96 week treatment period ]
  The difference in proportion of subjects with ≥ 1 severe or documented symptomatic hypoglycemia events in the bexagliflozin group compared with glimepiride group over 96 weeks is analyzed using a logistic regression model. The full model included region, baseline HbA1c value, background treatment status (metformin or metformin + OHA), eGFR at baseline ≥ 90 or < 90 mL min 1 per 1.73 m2), treatment as a fixed effect covariate.
• Superiority of Bexagliflozin Over Glimepiride in HbA1c Reduction at Week 60. [ Time Frame: Baseline to Week 60 ]
  Superiority of bexagliflozin over glimepiride in HbA1c reduction from baseline to week 60 will be declared if the upper bound of 95% CI is less than 0.

Original Secondary Outcome Measures (submitted: May 9, 2016)

• Change in body weight from baseline to week 60 in subjects with baseline body mass index (BMI) ≥ 25 kg/m2 [ Time Frame: Baseline and 60 weeks ]
• Change in systolic blood pressure (SBP) from baseline to week 60 in subjects with baseline SBP ≥ 140 mmHg [ Time Frame: Baseline and 60 weeks ]
• Difference in proportion of subjects with ≥ 1 severe or documented symptomatic hypoglycemia events over 96 weeks [ Time Frame: During the 96 week treatment period ]
• Change in HbA1c from baseline at week 60 [ Time Frame: During the 60 week treatment period ]

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: May 9, 2016)

• Safety of exposure to bexagliflozin for 96 weeks as assessed by analyzing treatment emergent adverse events, laboratory results, electrocardiogram parameters, physical examinations, vital signs and use of concomitant medications [ Time Frame: 96 weeks ]
• Effect of bexagliflozin on the incidence of adverse events of interest [ Time Frame: 96 weeks ]

Descriptive Information

• Brief Title: Safety and Efficacy of Bexagliflozin Compared to Glimepiride as Add-on Therapy to Metformin in Type 2 Diabetes Subjects
• Official Title: A Phase 3, Randomized, Double-blind, Active-controlled Study to Evaluate the Effects of Bexagliflozin Versus Glimepiride in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control by Metformin
• Brief Summary: The purpose of this study is to investigate the effect of bexagliflozin compared to glimepiride as an add-on therapy to metformin in lowering hemoglobin A1c (HbA1c) levels in subjects with type 2 diabetes mellitus (T2DM).
• Detailed Description: Approximately 420 subjects with inadequately controlled T2DM on metformin will be recruited from North America and Europe. Subjects will be randomly assigned to receive bexagliflozin tablets, 20 mg, or glimepiride capsules, 2, 4 or 6 mg, in a ratio of 1:1 once daily for 96 weeks. Subjects will continue to take metformin for the duration of the study.
• 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 Name: EGT0001442
• Drug: Placebo for Bexagliflozin
  inactive tablet to match active comparator bexagliflozin
• Drug: Glimepiride
  2, 4 or 6 mg, capsule
• Drug: Placebo for Glimepiride
  inactive capsules to match active comparator glimepiride

Study Arms

• Active Comparator: Bexagliflozin
  Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride daily for the duration of the study.
  Interventions:

  • Drug: Bexagliflozin
  • Drug: Placebo for Glimepiride
• Active Comparator: Glimepiride
  Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study.
  Interventions:

  • Drug: Placebo for Bexagliflozin
  • Drug: Glimepiride

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 25, 2021): 426
• Original Estimated Enrollment (submitted: May 9, 2016): 420
• Actual Study Completion Date: June 14, 2019
• Actual Primary Completion Date: June 14, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of T2DM
• Currently taking metformin or taking metformin and one additional oral medication for diabetes
• Body Mass Index (BMI) ≤ 45 kg/m2
• Stable dose of blood pressure or cholesterol medications (if applicable) for at least 30 days

Exclusion Criteria:

• Hypersensitivity or other contraindication to the safe use of sulfonylurea or glimepiride
• Diagnosis of type 1 diabetes mellitus or maturity-onset/diabetes of the young
• Current use of injected therapy for treatment of diabetes (insulin or GLP-1 receptor agonist therapy) or thiazolidinedione class drugs
• History of genitourinary tract infections
• Evidence of abnormal liver function
• Myocardial infarction, stroke or hospitalization for heart failure within 3 months of screening
• Prior kidney transplant or evidence of kidney problems
• Pregnant or nursing

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 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: Germany, Poland, Spain, United States

Administrative Information

• NCT Number: NCT02769481
• Other Study ID Numbers: THR-1442-C-480
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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 Sub, LLC

• PRS Account: Theracos
• Verification Date: May 2021