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

Registration Number
NCT03115112
Lead Sponsor
Theracos
Brief Summary

The purpose of this study is to investigate the effect of bexagliflozin compared to sitagliptin as an add-on therapy to metformin in lowering hemoglobin A1c (HbA1c) levels in subjects with type 2 diabetes mellitus (T2DM).

Detailed Description

This was a phase 3, multi-center, randomized, double-blind, parallel-group study to demonstrate that bexagliflozin was non-inferior to sitagliptin as add-on therapy in subjects whose T2DM was not adequately controlled by metformin treatment alone. The primary effectiveness endpoint was the change in HbA1c from baseline at week 24.

At the time of screening, all subjects were to have taken metformin at a stable dose of ≥ 1500 mg per day for ≥ 8 weeks and have received diet and exercise counseling. A total of 374 eligible subjects were to be enrolled in the study. Subjects who successfully completed a 1-week run-in and who met all eligibility criteria were to be randomized in a 1:1 ratio to receive once daily double-blind treatment of either active bexagliflozin tablets with placebo sitagliptin tablets or placebo bexagliflozin tablets and active sitagliptin tablets. The study subjects were to continue receiving open-labeled metformin during the entire study at a stable dose and frequency. The treatment period was 24 weeks and was conducted in an outpatient setting.

Randomization was stratified by HbA1c (≤ 8.5% vs. ˃ 8.5%) values. Symptoms and blood sugars related to the occurrence of hyperglycemia, hypoglycemic events or symptoms that could indicate ketoacidosis were to be recorded. Bexagliflozin tablets, 20 mg or placebo, and sitagliptin tablets, 100 mg or placebo, were to be taken once daily at approximately the same time each day either before or after breakfast. Background metformin was to be taken at the same dose and frequency from screening throughout the entire study.

Each subject was advised to return to the clinic at weeks 6, 12, 18 and 24 for efficacy assessment and safety monitoring, including review of AEs and concomitant medication, vital signs, ECG, physical examination and blood and urine specimen collections. Subjects were to return to the clinic for a follow-up exit visit at week 26 or 2 weeks after the last dose of study drugs if subjects withdrew from the study prior to week 24.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
386
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SitagliptinSitagliptinSubjects will receive a sitagliptin tablet, 100 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.
SitagliptinPlacebo for bexagliflozinSubjects will receive a sitagliptin tablet, 100 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.
BexagliflozinPlacebo for sitagliptinSubjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study.
BexagliflozinBexagliflozinSubjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for sitagliptin daily for the duration of the study.
Primary Outcome Measures
NameTimeMethod
Change in HbA1c From Baseline to Week 24Baseline to week 24

The primary efficacy objective is to demonstrate that bexagliflozin is non-inferior to sitagliptin by evaluating the treatment effect on hemoglobin A1c (HbA1c) reduction at week 24 in subjects whose type 2 diabetes mellitus (T2DM) is inadequately controlled by metformin.

Secondary Outcome Measures
NameTimeMethod
Change in FPG From Baseline at Week 24Baseline to week 24

To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in fasting plasma glucose (FPG) at week 24

Change in Body Weight in Subjects With Baseline BMI ≥ 25 kg/m2 at Week 24Baseline to week 24

To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in body weight in subjects with baseline body mass index (BMI) ≥ 25 kg/m2 at week 24

Change in SBP in Subjects From Baseline at Week 24Baseline to week 24

To evaluate the treatment effect of bexagliflozin vs. sitagliptin on the change in systolic blood pressure (SBP) in subjects at week 24

Trial Locations

Locations (56)

Clinical Research Site 7138

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Lublin, Poland

Clinical Research Site 7137

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Gdańsk, Poland

Clinical Research Site 7141

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Kraków, Poland

Clinical Research Site 9107

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Szeged, Hungary

Clinical Research Site 9105

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Zalaegerszeg, Hungary

Clinical Research Site 7142

🇵🇱

Kraków, Poland

Clinical Research Site 7128

🇵🇱

Toruń, Poland

Clinical Research Site 7139

🇵🇱

Kraków, Poland

Clinical Research Site 7140

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Poznań, Poland

Clinical Research Site 1357

🇺🇸

Lincoln, California, United States

Clinical Research Site 1361

🇺🇸

San Dimas, California, United States

Clinical Research Site 1271

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Chicago, Illinois, United States

Clinical Research Site 3123

🇨🇿

Mladá Boleslav, Czechia

Clinical Research Site 3120

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Olomouc, Czechia

Clinical Research Site 7144

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Kraków, Poland

Clinical Research Site 9013

🇪🇸

Barcelona, Spain

Clinical Research Site 9018

🇪🇸

Valencia, Spain

Clinical Research Site 6039

🇯🇵

Ibaraki, Japan

Clinical Research Site 6038

🇯🇵

Tochigi, Japan

Clinical Research Site 7120

🇵🇱

Lublin, Poland

Clinical Research Site 1358

🇺🇸

Long Beach, California, United States

Clinical Research Site 1359

🇺🇸

Topeka, Kansas, United States

Clinical Research Site 1031

🇺🇸

Port Orange, Florida, United States

Clinical Research Site 1009

🇺🇸

Berlin, New Jersey, United States

Clinical Research Site 1360

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San Antonio, Texas, United States

Clinical Research Site 1008

🇺🇸

Munroe Falls, Ohio, United States

Clinical Research Site 3119

🇨🇿

Hodonín, Czechia

Clinical Research Site 9102

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Balatonfüred, Hungary

Clinical Research Site 3122

🇨🇿

Prostějov, Czechia

Clinical Research Site 3112

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Praha, Czechia

Clinical Research Site 9101

🇭🇺

Balatongyörök, Hungary

Clinical Research Site 9103

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Zamardi, Hungary

Clinical Research Site 9106

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Budapest, Hungary

Clinical Research Site 6042

🇯🇵

Chiba, Japan

Clinical Research Site 6037

🇯🇵

Chiba, Japan

Clinical Research Site 6040

🇯🇵

Fukuoka, Japan

Clinical Research Site 6031

🇯🇵

Chiba, Japan

Clinical Research Site 6035

🇯🇵

Fukuoka, Japan

Clinical Research Site 6034

🇯🇵

Ibaraki, Japan

Clinical Research Site 6041

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Ibaraki, Japan

Clinical Research Site 6032

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Ibaraki, Japan

Clinical Research Site 6036

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Shizuoka, Japan

Clinical Research Site 6033

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Ōsaka, Japan

Clinical Research Site 7131

🇵🇱

Olsztyn, Poland

Clinical Research Site 7143

🇵🇱

Poznań, Poland

Clinical Research Site 7107

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Puławy, Poland

Clinical Research Site 7136

🇵🇱

Poznań, Poland

Clinical Research Site 9002

🇪🇸

Alicante, Spain

Clinical Research Site 9016

🇪🇸

Almería, Spain

Clinical Research Site 9005

🇪🇸

Alzira, Spain

Clinical Research Site 9017

🇪🇸

Barcelona, Spain

Clinical Research Site 9015

🇪🇸

Sevilla, Spain

Clinical Research Site 9012

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Madrid, Spain

Clinical Research Site 9014

🇪🇸

Sevilla, Spain

Clinical Research Site 9011

🇪🇸

Sevilla, Spain

Clinical Research Site 1037

🇺🇸

Trenton, New Jersey, United States

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