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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02769481
• Other study ID #: THR-1442-C-480
• Status: Completed
• Phase: Phase 3
• Start date: August 15, 2016
• Est. completion date: June 14, 2019

Study information

• Verified date: May 2021
• Source: Theracos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 426
• Est. completion date: June 14, 2019
• Est. primary completion date: June 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Bexagliflozin
20 mg, tablet
• Placebo for Bexagliflozin
inactive tablet to match active comparator bexagliflozin
• Glimepiride
2, 4 or 6 mg, capsule
• Placebo for Glimepiride
inactive capsules to match active comparator glimepiride

Locations

Country	Name	City	State
Germany	Research Site	Aschaffenburg
Germany	Research Site	Essen
Germany	Research Site 2	Essen
Germany	Research Site	Hamburg
Germany	Research Site 2	Hamburg
Germany	Research Site	Heidelberg
Germany	Research Site	Magdeburg
Germany	Research Site	Wangen
Poland	Research Site	Bochnia
Poland	Research Site	Bydgoszcz
Poland	Research Site	Kraków
Poland	Research Site 2	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site 2	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Poznan
Poland	Research Site	Pulawy
Poland	Research Site	Staszów
Poland	Research Site	Swarzedz
Poland	Research Site	Swidnik
Poland	Research Site	Torun
Poland	Research Site	Warszawa
Poland	Research Site	Zamosc
Spain	Research Site	Alicante
Spain	Research Site	Barcelona
Spain	Research Site 2	Barcelona
Spain	Research Site	Madrid
Spain	Research Site 2	Madrid
Spain	Research Site 3	Madrid
Spain	Research Site	Malaga
Spain	Research Site 2	Malaga
Spain	Research Site 2	Oviedo
Spain	Research Site	Valencia
United States	Research Site	Birmingham	Alabama
United States	Research Site	Calabash	North Carolina
United States	Research Site	Hialeah	Florida
United States	Research Site	Huntington Park	California
United States	Research Site	Los Angeles	California
United States	Research Site	Magnolia	Texas
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Morehead City	North Carolina
United States	Research Site	Orlando	Florida
United States	Research Site	San Carlos	California
United States	Research Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Theracos

Countries where clinical trial is conducted

United States,  Germany,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c at 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).	Baseline and Week 60
Secondary	Change From Baseline in Body Weight at Week 60 for Subjects With Baseline BMI = 25 kg/m2	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.	Baseline and 60 weeks
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) at Week 60 for Subjects With Baseline SBP = 140 mmHg	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.	Baseline and 60 weeks
Secondary	Difference in Proportion of Subjects With = 1 Severe or Documented Symptomatic Hypoglycemia Events Over 96 Weeks	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.	During the 96 week treatment period
Secondary	Superiority of Bexagliflozin Over Glimepiride in HbA1c Reduction at 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.	Baseline to Week 60