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

NCT03115112 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: THR-1442-C-423
• Study Type: interventional
• Target: 386
• Locations: 6 countries
• Sites: 56

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).

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c From Baseline 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.

  Baseline to week 24

Secondary Outcomes (3)

• Change in FPG From Baseline at Week 24

  Baseline to week 24

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

  Baseline to week 24

• Change in SBP in Subjects From Baseline at Week 24

  Baseline to week 24

Study Arms (2)

Bexagliflozin

ACTIVE COMPARATOR

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.

Drug: Bexagliflozin; Drug: Placebo for sitagliptin

Sitagliptin

ACTIVE COMPARATOR

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.

Drug: Sitagliptin; Drug: Placebo for bexagliflozin

Interventions

Bexagliflozin DRUG

tablets containing 20 mg bexagliflozin

Also known as: EGT0001442, EGT0001474

Bexagliflozin

Sitagliptin DRUG

tablets containing 100 mg sitagliptin

Also known as: Januvia

Sitagliptin

Placebo for sitagliptin DRUG

inactive tablets to match the appearance of sitagliptin tablets

Bexagliflozin

Placebo for bexagliflozin DRUG

inactive tablets to match the appearance of bexagliflozin tablets

Sitagliptin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Each subject was required to meet the following criteria at the time of enrollment to be eligible for the study: 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Theracos: lead

Study Sites (56)

Clinical Research Site 1357

Lincoln, California, 95648, United States

Location

Clinical Research Site 1358

Long Beach, California, 90806, United States

Location

Clinical Research Site 1361

San Dimas, California, 91773, United States

Location

Clinical Research Site 1031

Port Orange, Florida, 32127, United States

Location

Clinical Research Site 1271

Chicago, Illinois, 60611, United States

Location

Clinical Research Site 1359

Topeka, Kansas, 66606, United States

Location

Clinical Research Site 1009

Berlin, New Jersey, 08009, United States

Location

Clinical Research Site 1037

Trenton, New Jersey, 08611, United States

Location

Clinical Research Site 1008

Munroe Falls, Ohio, 44262, United States

Location

Clinical Research Site 1360

San Antonio, Texas, 78258, United States

Location

Clinical Research Site 3119

Hodonín, 695 00, Czechia

Location

Clinical Research Site 3123

Mladá Boleslav, 293 01, Czechia

Location

Clinical Research Site 3120

Olomouc, 779 00, Czechia

Location

Clinical Research Site 3112

Prague, 181 00, Czechia

Location

Clinical Research Site 3122

Prostějov, 796 01, Czechia

Location

Clinical Research Site 9102

Balatonfüred, Hungary

Location

Clinical Research Site 9101

Balatongyörök, Hungary

Location

Clinical Research Site 9106

Budapest, Hungary

Location

Clinical Research Site 9107

Szeged, Hungary

Location

Clinical Research Site 9105

Zalaegerszeg, Hungary

Location

Clinical Research Site 9103

Zamárdi, Hungary

Location

Clinical Research Site 6031

Chiba, 260-0804, Japan

Location

Clinical Research Site 6037

Chiba, 272-8516, Japan

Location

Clinical Research Site 6042

Chiba, 277-0825, Japan

Location

Clinical Research Site 6040

Fukuoka, 819-0006, Japan

Location

Clinical Research Site 6035

Fukuoka, 819-0168, Japan

Location

Clinical Research Site 6034

Ibaraki, 300-0835, Japan

Location

Clinical Research Site 6039

Ibaraki, 300-1207, Japan

Location

Clinical Research Site 6041

Ibaraki, 306-0232, Japan

Location

Clinical Research Site 6032

Ibaraki, 310-0826, Japan

Location

Clinical Research Site 6033

Ōsaka, 582-0005, Japan

Location

Clinical Research Site 6036

Shizuoka, 424-0855, Japan

Location

Clinical Research Site 6038

Tochigi, 323-0022, Japan

Location

Clinical Research Site 7137

Gdansk, 80-858, Poland

Location

Clinical Research Site 7144

Krakow, 30-015, Poland

Location

Clinical Research Site 7142

Krakow, 31-209, Poland

Location

Clinical Research Site 7139

Krakow, 31-261, Poland

Location

Clinical Research Site 7141

Krakow, 31-530, Poland

Location

Clinical Research Site 7120

Lublin, 20-362, Poland

Location

Clinical Research Site 7138

Lublin, 20-538, Poland

Location

Clinical Research Site 7131

Olsztyn, 10-117, Poland

Location

Clinical Research Site 7143

Poznan, 60-819, Poland

Location

Clinical Research Site 7140

Poznan, 60-821, Poland

Location

Clinical Research Site 7136

Poznan, 61-655, Poland

Location

Clinical Research Site 7107

Puławy, 24-100, Poland

Location

Clinical Research Site 7128

Torun, 87-100, Poland

Location

Clinical Research Site 9002

Alicante, 03004, Spain

Location

Clinical Research Site 9016

Almería, 04001, Spain

Location

Clinical Research Site 9005

Alzira, 46600, Spain

Location

Clinical Research Site 9017

Barcelona, 08023, Spain

Location

Clinical Research Site 9013

Barcelona, 08500, Spain

Location

Clinical Research Site 9012

Madrid, 28007, Spain

Location

Clinical Research Site 9011

Seville, 41009, Spain

Location

Clinical Research Site 9014

Seville, 41013, Spain

Location

Clinical Research Site 9015

Seville, Spain

Location

Clinical Research Site 9018

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

bexagliflozin; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Albert Collinson
• Organization: Theracos Sub, LLC

acollinson@theracos.com

(508) 630-2129

Study Officials

• J. Paul Lock, MD

  Theracos Sub, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 14, 2017
• Study Start: October 12, 2017
• Primary Completion: October 31, 2018
• Study Completion: October 31, 2018
• Last Updated: June 22, 2021
• Results First Posted: June 4, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

JP (12); PL (13); CZ (5); ES (10); US (10); HU (6)