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

NCT03259789 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: THR-1442-C-419
• Study Type: interventional
• Target: 351
• Locations: 2 countries
• Sites: 43

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).

Conditions

Type2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in HbA1c at Week 24 for Double-blind Group

  HbA1c was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.

  Baseline to week 24

• Change From Baseline in HbA1c at Week 24 for High Glycemic Group

  The change in HbA1c from baseline at Week 24 in High Glycemic Group was calculated by subtracting the mean HbA1c at baseline from the mean HbA1c at Week 24

  Baseline to week 24

Secondary Outcomes (9)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for Double-blind Group

  Baseline, up to 24 weeks

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for High Glycemic Group

  Baseline, up to 24 weeks

• Change From Baseline in Systolic Blood Pressure (SBP) at Week 24

  Baseline to week 24

• Proportion of Subjects Achieving HbA1c < 7% Over Time for Double-blind Group

  Baseline, up to 24 weeks

• Proportion of Subjects Achieving HbA1c < 7% Over Time for High Glycemic Group

  Baseline, up to 24 weeks

Study Arms (3)

Bexagliflozin tablets, 20 mg; Double-Blind

ACTIVE COMPARATOR

Drug: Bexagliflozin tablets, 20 mg

Bexagliflozin tablets, Placebo; Double Blind

PLACEBO COMPARATOR

Drug: Bexagliflozin tablets, placebo

Bexagliflozin Tablets, 20 mg; High Glycemic Group

EXPERIMENTAL

Drug: Bexagliflozin tablets, 20 mg

Interventions

Bexagliflozin tablets, 20 mg DRUG

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

Also known as: EGT0001442, EGT0001474

Bexagliflozin tablets, 20 mg; Double-Blind

Bexagliflozin tablets, placebo DRUG

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

Bexagliflozin tablets, Placebo; Double Blind

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

The subjects were required to meet the following criteria at the time of enrollment to be eligible for the study: 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

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 (43)

Clinical Research Site 1232

Birmingham, Alabama, 35205, United States

Location

Clinical Research Site 1378

Birmingham, Alabama, 35242, United States

Location

Clinical Research Site 1269

Foley, Alabama, 36535, United States

Location

Clinical Research Site 1363

Little Rock, Arkansas, 72209, United States

Location

Clinical Research Site 1381

Anaheim, California, 92805, United States

Location

Clinical Research Site 1375

North Hollywood, California, 91606, United States

Location

Clinical Research Site 1365

Norwalk, California, 90650, United States

Location

Clinical Research Site 1382

Norwalk, Connecticut, 06851, United States

Location

Clinical Research Site 1372

Hollywood, Florida, 33024, United States

Location

Clinical Research Site 1362

Palm Springs, Florida, 33461, United States

Location

Clinical Research Site 1373

Pembroke Pines, Florida, 33026, United States

Location

Clinical Research Site 1376

Nampa, Idaho, 83686, United States

Location

Clinical Research Site 1366

Chicago, Illinois, 60602, United States

Location

Clinical Research Site 1294

New Orleans, Louisiana, 70124, United States

Location

Clinical Research Site 1374

St Louis, Missouri, 63117, United States

Location

Clinical Research Site 1370

Las Vegas, Nevada, 89104, 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 1286

Albuquerque, New Mexico, 87102, United States

Location

Clinical Research Site 1368

New York, New York, 10036, United States

Location

Clinical Research Site 1275

The Bronx, New York, 10455, United States

Location

Clinical Research Site 1019

Portland, Oregon, 97239, United States

Location

Clinical Research Site 1379

Gonzales, Texas, 78629, United States

Location

Clinical Research Site 1369

Houston, Texas, 77051, United States

Location

Clinical Research Site 1371

San Antonio, Texas, 78209, United States

Location

Clinical Research Site 1360

San Antonio, Texas, 78258, United States

Location

Clinical Research Site 6048

Nagoya, Aichi-ken, 456-0058, Japan

Location

Clinical Research Site 6050

Sapporo, Hokkaido, 003-0023, Japan

Location

Clinical Research Site 6041

Koga, Ibaraki, 306-0232, Japan

Location

Clinical Research Site 6029

Atsugi, Kanagawa, 243-0035, Japan

Location

Clinical Research Site 6051

Kamakura, Kanagawa, 547-0055, Japan

Location

Clinical Research Site 6020

Yokohama, Kanagawa, 221-080, Japan

Location

Clinical Research Site 6055

Tokyo, Meguro, 153-0053, Japan

Location

Clinical Research Site 6046

Higashiosaka, Osaka, 577-0803, Japan

Location

Clinical Research Site 6033

Kashihara, Osaka, 582-0005, Japan

Location

Clinical Research Site 6013

Toyonaka, Osaka, 560-0082, Japan

Location

Clinical Research Site 6052

Kawaguchi, Saitama, 332-0012, Japan

Location

Clinical Research Site 6053

Shimotsuke, Tochigi, 329-0433, Japan

Location

Clinical Research Site 6040

Fukuoka, 819-0006, Japan

Location

Clinical Research Site 6043

Kyoto, 600-8898, Japan

Location

Clinical Research Site 6015

Osaka, 536-0008, Japan

Location

Clinical Research Site 6045

Tokyo, 108-0075, Japan

Location

Clinical Research Site 6047

Tokyo, 166-0003, Japan

Location

MeSH Terms

Interventions

bexagliflozin

Results Point of Contact

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

acollinson@theracos.com

(508) 630-2129

Study Officials

• J, Paul Lock, M.D.

  Theracos

  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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 24, 2017
• Study Start: November 28, 2017
• Primary Completion: January 23, 2019
• Study Completion: January 23, 2019
• Last Updated: July 7, 2021
• Results First Posted: July 7, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (17); US (26)