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

NCT ID: NCT03115112

Last Updated: 2021-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 386 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-12
• Study Completion Date: 2018-10-31

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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 sitagliptin daily for the duration of the study.

Group Type: ACTIVE_COMPARATOR

Bexagliflozin

Intervention Type: DRUG

tablets containing 20 mg bexagliflozin

Placebo for sitagliptin

Intervention Type: DRUG

inactive tablets to match the appearance of sitagliptin tablets

Sitagliptin

Subjects 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.

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: DRUG

tablets containing 100 mg sitagliptin

Placebo for bexagliflozin

Intervention Type: DRUG

inactive tablets to match the appearance of bexagliflozin tablets

Interventions

Bexagliflozin

tablets containing 20 mg bexagliflozin

Intervention Type: DRUG

Sitagliptin

tablets containing 100 mg sitagliptin

Intervention Type: DRUG

Placebo for sitagliptin

inactive tablets to match the appearance of sitagliptin tablets

Intervention Type: DRUG

Placebo for bexagliflozin

inactive tablets to match the appearance of bexagliflozin tablets

Intervention Type: DRUG

Other Intervention Names

EGT0001442, EGT0001474; Januvia

Eligibility Criteria

Inclusion Criteria

1. To have been male or female adults ≥ 18 years of age.

2. To have been negative on the urine pregnancy test and agreed to abstain from coitus or use contraception during the entire study if a subject was female of childbearing potential.

3. To have had a diagnosis of T2DM with HbA1c levels between 7.0% and 11% (inclusive) at the time of screening.

4. To have been treated with a stable dose of ≥ 1500 mg/day metformin only along with diet and exercise counseling for at least 8 weeks at the time of screening.

5. To have had a BMI ≤ 45 kg per m2 at the time of screening.

6. To have been taking stable doses of treatment for dyslipidemia and/or hypertension for 30 days if applicable.

7. To have been willing and able to return for all clinic visits and to complete all study-required procedures.

8. To have adhered to the investigational product administration requirements as evidenced by missing no more than 1 day of run-in medications.

Potential subjects who exhibited any of the following characteristics were to be excluded from the study:

1. Diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young (MODY)

2. Hemoglobinopathy that affected HbA1c measurement

3. Any contraindication to the safe use of DPP-4 therapy or sitagliptin, including known hypersensitivity reaction

4. History of pancreatitis

5. Genitourinary tract infection within 6 weeks of screening or history of ≥ 3 genitourinary infections requiring treatment within 6 months from the time of screening

6. Cancer, active or in remission, for < 3 years

7. History of alcohol or illicit drug abuse in the past 2 years

8. Triglycerides > 500 mg dL-1 at Visit V1

9. Evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase > 1.5 x upper limit of normal (ULN) with the exception of isolated Gilbert's syndrome); or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULN

10. Estimated GFR, as calculated by the modification of diet in renal disease study equation (MDRD), < 60 mL min-1 per 1.73 m2 at the time of screening.

11. Uncontrolled hypertension (SBP > 160 mm Hg or diastolic BP > 95 mm Hg) at Visit V1

12. Life expectancy < 2 years

13. History of MI, unstable angina, stroke or hospitalization for heart failure within 3 months at the time of screening

14. History of treatment with an investigational drug within 30 days or within 7 half-lives of the investigational drug, whichever is longer

15. Previous treatment with bexagliflozin or EGT0001474 study drug

16. Currently or within 3 months of taking any SGLT2 inhibitor

17. Currently participating in another interventional trial

18. Prior renal transplantation or evidence of nephrotic syndrome (defined as a urine albumin-to-creatinine ratio (UACR) > 1500 mg g-1 at the time of screening).

19. Any condition, disease, disorder or clinically relevant abnormality that could have jeopardized the subject's appropriate participation in this study or obscure the effects of treatment

20. Female subjects who were pregnant or nursing

21. Two or more consecutive SMBG measures ≥ 250 mg dL-1 (13.9 mmol L-1) prior to randomization accompanied by clinical signs or symptoms of hyperglycemia prior to randomization, including weight loss, blurred vision, increased thirst increased urination, or fatigue

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theracos

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

J. Paul Lock, MD

Role: STUDY_DIRECTOR

Theracos Sub, LLC

Locations

Clinical Research Site 1357

Lincoln, California, United States

Clinical Research Site 1358

Long Beach, California, United States

Clinical Research Site 1361

San Dimas, California, United States

Clinical Research Site 1031

Port Orange, Florida, United States

Clinical Research Site 1271

Chicago, Illinois, United States

Clinical Research Site 1359

Topeka, Kansas, United States

Clinical Research Site 1009

Berlin, New Jersey, United States

Clinical Research Site 1037

Trenton, New Jersey, United States

Clinical Research Site 1008

Munroe Falls, Ohio, United States

Clinical Research Site 1360

San Antonio, Texas, United States

Clinical Research Site 3119

Hodonín, , Czechia

Clinical Research Site 3123

Mladá Boleslav, , Czechia

Clinical Research Site 3120

Olomouc, , Czechia

Clinical Research Site 3112

Prague, , Czechia

Clinical Research Site 3122

Prostějov, , Czechia

Clinical Research Site 9102

Balatonfüred, , Hungary

Clinical Research Site 9101

Balatongyörök, , Hungary

Clinical Research Site 9106

Budapest, , Hungary

Clinical Research Site 9107

Szeged, , Hungary

Clinical Research Site 9105

Zalaegerszeg, , Hungary

Clinical Research Site 9103

Zamárdi, , Hungary

Clinical Research Site 6031

Chiba, , Japan

Clinical Research Site 6037

Chiba, , Japan

Clinical Research Site 6042

Chiba, , Japan

Clinical Research Site 6040

Fukuoka, , Japan

Clinical Research Site 6035

Fukuoka, , Japan

Clinical Research Site 6034

Ibaraki, , Japan

Clinical Research Site 6039

Ibaraki, , Japan

Clinical Research Site 6041

Ibaraki, , Japan

Clinical Research Site 6032

Ibaraki, , Japan

Clinical Research Site 6033

Ōsaka, , Japan

Clinical Research Site 6036

Shizuoka, , Japan

Clinical Research Site 6038

Tochigi, , Japan

Clinical Research Site 7137

Gdansk, , Poland

Clinical Research Site 7144

Krakow, , Poland

Clinical Research Site 7142

Krakow, , Poland

Clinical Research Site 7139

Krakow, , Poland

Clinical Research Site 7141

Krakow, , Poland

Clinical Research Site 7120

Lublin, , Poland

Clinical Research Site 7138

Lublin, , Poland

Clinical Research Site 7131

Olsztyn, , Poland

Clinical Research Site 7143

Poznan, , Poland

Clinical Research Site 7140

Poznan, , Poland

Clinical Research Site 7136

Poznan, , Poland

Clinical Research Site 7107

Puławy, , Poland

Clinical Research Site 7128

Torun, , 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 9013

Barcelona, , Spain

Clinical Research Site 9012

Madrid, , Spain

Clinical Research Site 9011

Seville, , Spain

Clinical Research Site 9014

Seville, , Spain

Clinical Research Site 9015

Seville, , Spain

Clinical Research Site 9018

Valencia, , Spain

Countries

United States; Czechia; Hungary; Japan; Poland; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

THR-1442-C-423

Identifier Type: -

Identifier Source: org_study_id