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

NCT ID: NCT03259789

Last Updated: 2021-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 351 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-28
• Study Completion Date: 2019-01-23

Brief Summary

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

Detailed Description

Approximately 300 subjects with inadequately controlled T2DM on metformin were to be recruited from the United States and Japan. Subjects were randomly assigned to receive bexagliflozin tablets, 20 mg, or bexagliflozin tablets, placebo, in a ratio of 1:1 once daily for 24 weeks. Subjects were to continue taking metformin for the duration of the study. The study also enrolled 50 subjects with extremely poorly controlled T2DM on metformin to receive open-label bexagliflozin tablets, 20 mg, for 24 weeks.

Conditions

Type2 Diabetes Mellitus

Study Design

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

Study Groups

Bexagliflozin tablets, 20 mg; Double-Blind

Group Type: ACTIVE_COMPARATOR

Bexagliflozin tablets, 20 mg

Intervention Type: DRUG

Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.

Bexagliflozin tablets, Placebo; Double Blind

Group Type: PLACEBO_COMPARATOR

Bexagliflozin tablets, placebo

Intervention Type: DRUG

Each subject will receive placebo (inactive tablet) once daily for the duration of the study.

Bexagliflozin Tablets, 20 mg; High Glycemic Group

Group Type: EXPERIMENTAL

Bexagliflozin tablets, 20 mg

Intervention Type: DRUG

Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.

Interventions

Bexagliflozin tablets, 20 mg

Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.

Intervention Type: DRUG

Bexagliflozin tablets, placebo

Each subject will receive placebo (inactive tablet) once daily for the duration of the study.

Intervention Type: DRUG

Bexagliflozin tablets, 20 mg

Each subject will receive bexagliflozin, 20 mg once daily for the duration of the study.

Intervention Type: DRUG

Other Intervention Names

EGT0001442, EGT0001474; EGT0001442, EGT0001474

Eligibility Criteria

Inclusion Criteria

1. Had been age ≥ 20 years at screening. Women of childbearing potential were required to have tested negative for pregnancy and have agreed to abstinence or contraception for the duration of the study to avoid any possible pregnancy. Females who were surgically sterile (hysterectomy, oophorectomy) or postmenopausal (absence of menses greater than 12 months) were eligible if they had tested negative for pregnancy at screening.

2. a) Had a history of T2DM with an HbA1c level of ≥ 7.5% and ≤ 10.5% at screening, or b) Had a history of T2DM with an HbA1c level of >10.5% and ≤ 12.0% at screening

3. Had been prescribed a stable dose of metformin (≥1500 mg per day in the US or ≥ 1000 mg per day in Japan) as their sole anti-diabetic medication

4. Had a body mass index (BMI) ≤ 45 kg m-2

5. Had been able to comprehend and willing to provide written informed consent in accordance with institutional and regulatory guidelines

6. Had no recent changes to their medications for hypertension or hyperlipidemia (if applicable)

7. Had the ability to regularly self-administer medication, as evidenced by consumption of all, or at worst one less than all, doses of run-in medication prior to randomization

Subjects who met any of the following criteria were to be excluded from the study:

1. Had a diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young

2. Were pregnant or breastfeeding

3. Had one or more hemoglobin alleles that affect HbA1c measurement

4. Had a history of genitourinary tract infection (e.g., UTI, GMI, vaginitis, balanitis) within 6 weeks of screening or a history of ≥ 3 genitourinary infections requiring treatment within 6 months of screening

5. Had an estimated glomerular filtration rate (eGFR), as calculated by the modification of diet in renal disease study equation (MDRD), < 60 mL min-1 per 1.73 m2

6. Had a sitting systolic blood pressure >180 mmHg or a sitting diastolic blood pressure > 110 mmHg at screening

7. Had exposure to hypoglycemic agent(s) other than metformin during the 8 weeks prior to screening

8. Had a history of illicit drug use or alcohol abuse in the past 2 years

9. Had a life expectancy < 2 years

10. Had a diagnosis of New York Heart Association (NYHA) Class IV heart failure within 3 months of screening

11. Had experienced an MI, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening

12. Had exposure to an investigational drug within 30 days

13. Had a previous exposure to bexagliflozin or EGT0001474

14. Had a history of SGLT2 inhibitor treatment

15. Were participating in another interventional trial

16. Were not able to comply with the study scheduled visits

17. Had any condition, disease, disorder, or clinically relevant abnormality that, in the opinion of the primary investigator, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment

18. Had an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 × ULN or total bilirubin ≥ 1.5 × ULN at screening

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theracos

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

J, Paul Lock, M.D.

Role: STUDY_DIRECTOR

Theracos

Locations

Clinical Research Site 1232

Birmingham, Alabama, United States

Clinical Research Site 1378

Birmingham, Alabama, United States

Clinical Research Site 1269

Foley, Alabama, United States

Clinical Research Site 1363

Little Rock, Arkansas, United States

Clinical Research Site 1381

Anaheim, California, United States

Clinical Research Site 1375

North Hollywood, California, United States

Clinical Research Site 1365

Norwalk, California, United States

Clinical Research Site 1382

Norwalk, Connecticut, United States

Clinical Research Site 1372

Hollywood, Florida, United States

Clinical Research Site 1362

Palm Springs, Florida, United States

Clinical Research Site 1373

Pembroke Pines, Florida, United States

Clinical Research Site 1376

Nampa, Idaho, United States

Clinical Research Site 1366

Chicago, Illinois, United States

Clinical Research Site 1294

New Orleans, Louisiana, United States

Clinical Research Site 1374

St Louis, Missouri, United States

Clinical Research Site 1370

Las Vegas, Nevada, United States

Clinical Research Site 1009

Berlin, New Jersey, United States

Clinical Research Site 1037

Trenton, New Jersey, United States

Clinical Research Site 1286

Albuquerque, New Mexico, United States

Clinical Research Site 1368

New York, New York, United States

Clinical Research Site 1275

The Bronx, New York, United States

Clinical Research Site 1019

Portland, Oregon, United States

Clinical Research Site 1379

Gonzales, Texas, United States

Clinical Research Site 1369

Houston, Texas, United States

Clinical Research Site 1371

San Antonio, Texas, United States

Clinical Research Site 1360

San Antonio, Texas, United States

Clinical Research Site 6048

Nagoya, Aichi-ken, Japan

Clinical Research Site 6050

Sapporo, Hokkaido, Japan

Clinical Research Site 6041

Koga, Ibaraki, Japan

Clinical Research Site 6029

Atsugi, Kanagawa, Japan

Clinical Research Site 6051

Kamakura, Kanagawa, Japan

Clinical Research Site 6020

Yokohama, Kanagawa, Japan

Clinical Research Site 6055

Tokyo, Meguro, Japan

Clinical Research Site 6046

Higashiosaka, Osaka, Japan

Clinical Research Site 6033

Kashihara, Osaka, Japan

Clinical Research Site 6013

Toyonaka, Osaka, Japan

Clinical Research Site 6052

Kawaguchi, Saitama, Japan

Clinical Research Site 6053

Shimotsuke, Tochigi, Japan

Clinical Research Site 6040

Fukuoka, , Japan

Clinical Research Site 6043

Kyoto, , Japan

Clinical Research Site 6015

Osaka, , Japan

Clinical Research Site 6045

Tokyo, , Japan

Clinical Research Site 6047

Tokyo, , Japan

Countries

United States; Japan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

THR-1442-C-419

Identifier Type: -

Identifier Source: org_study_id