Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment

NCT ID: NCT02836873

Last Updated: 2021-06-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 312 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-23
• Study Completion Date: 2018-01-11

Brief Summary

This was a phase 3, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of oral administration of bexagliflozin at 20 mg versus placebo in subjects with T2DM, moderate renal impairment and inadequate glycemic control.

Detailed Description

The phase 3, double-blind, placebo-controlled parallel-group study was conducted at investigative sites in the US, Japan, France and Spain. Approximately 300 subjects were to be randomly assigned to receive bexagliflozin tablets, 20 mg, or placebo in equal ratio for 24 weeks.

The study was to enrolled male and female participants who had T2DM with an HbA1c between 7.0 and 10.5% (inclusive) and stage 3 chronic kidney disease (CKD) as defined by an eGFR of ≥ 30 and< 60 mL min-1 per 1.73 m2 at the screening visit and one additional time of measurement between 1 and 12 months prior to screening. Subjects were either treatment naïve or were treated with a stable regimen of anti-diabetic medications.

All eligible subjects were to enter a one-week single-blind, placebo run-in period. Subjects who were compliant in taking run-in medication, had screening eGFR ≥ 30 and< 60 mL min-1 per 1.73 m2, and had stable GFR (no more than 20% change in eGFR between a historical value and the value determined at the screening visit) were eligible for randomization. Randomization was stratified by HbA1c level (7.0 to 8.5% or 8.6 to 10.5%), anti-diabetic treatment regimen and eGFR (30 - 44 mL min-1 per 1.73 m2 or 45 - 59 mL min-1 per 1.73 m2). At least 135 subjects in each of the eGFR groups were planned.

Study subjects were to schedule clinic visits at weeks 2, 6, 12, 18, and 24 for safety and efficacy evaluation. At weeks 2 and 18, the visits were to be conducted via phone interviews unless an in-person visit was considered clinically advisable. A final follow-up visit was to be conducted at week 26 or two weeks after the last dose of investigational product if the subject withdrew prior to week 24.

Conditions

Type 2 Diabetes Mellitus

Study Design

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

Study Groups

Bexagliflozin tablets, 20 mg

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

Group Type: ACTIVE_COMPARATOR

Bexagliflozin

Intervention Type: DRUG

Bexagliflozin tablet, 20 mg

Placebo tablets

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo (inactive) tablet to match the active comparator

Interventions

Bexagliflozin

Bexagliflozin tablet, 20 mg

Intervention Type: DRUG

Placebo

Placebo (inactive) tablet to match the active comparator

Intervention Type: DRUG

Other Intervention Names

EGT0001442; EGT0001474

Eligibility Criteria

Inclusion Criteria

1. To have been male or non-pregnant female ≥ 20 years of age. Women of childbearing potential were required to agree to use contraception throughout the study to avoid any possible pregnancy. Females who were surgically sterile (hysterectomy, oophorectomy) or postmenopausal (absence of menses for greater than 12 months and age > 45 years) were eligible if they tested negative on the urine pregnancy test.

2. To have had a diagnosis of T2DM with an HbA1c between 7.0 and 10.5% (inclusive) at the time of screening.

3. To have been treatment naïve or to have been treated with a stable regimen of anti-diabetic medications. At the time of screening, the doses and frequency of all anti-diabetic medications were to have been stable for 8 weeks.

4. To have had an eGFR ≥ 30 and < 60 mL min-1 per 1.73 m2 at 2 time points: screening (V1), and 1 additional time point between 1 and 12 months of screening (may be obtained from available medical records). The eGFR was calculated by the MDRD equation.

5. To have had a body mass index (BMI) ≤ 45 kg per m2 (inclusive).

6. To have been taking stable doses of medications for hypertension or hyperlipidemia (if applicable) for at least 30 days prior to randomization

7. To have had stable eGFR between the historic value and day of screening (no more than 20% change in eGFR between the most recent historical value and the value determined at the screening visit V1).

Exclusion Criteria

Potential participants who exhibited any of the following characteristics were excluded from the study:

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

2. A hemoglobinopathy that could affect HbA1c measurement

3. Frequent symptomatic hypoglycemia (greater than one episode per week on average)

4. A history of genitourinary tract infection within 6 weeks of screening or history of ≥ 3 genitourinary infections requiring treatment within the last 6 months

5. A cancer, active or in remission for < 3 years (Non-melanoma skin cancer or basal cell carcinoma or carcinoma in situ of the cervix were not grounds for exclusion)

6. A history of alcohol or illicit drug abuse in the past 2 years

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

8. A history of MI, stroke or hospitalization for heart failure, or hospitalization for unstable angina in the prior 3 months

9. Evidence of NYHA class IV heart failure at screening or randomization

10. A history of taking an SGLT2 inhibitor within 3 months of screening

11. Any condition, disease, disorder, or clinically relevant laboratory abnormality that, in the opinion of the PI, would jeopardize the subject's appropriate participation in this study or obscure the effects of treatment

12. A current status of pregnancy or breastfeeding

13. A current status of renal replacement therapy (peritoneal or hemodialysis) or a history of renal transplantation

14. A corrected serum calcium < 8 mg dL-1 at screening (V1) or randomization (V3)

15. Uncontrolled hypertension (systolic blood pressure >170 mm Hg or diastolic blood pressure >110 mm Hg)

16. Participation in another interventional trial or exposure to an investigational drug within 30 days or 7 half-lives of screening, whichever was longer

17. Previous exposure to bexagliflozin or EGT0001474

18. Evidence of having skipped dosing more than once during the run-in period

19. A fasting blood glucose value during the run-in period ≥ 250 mg dL-1 (13.9 mmol L-1) associated with severe clinical signs or symptoms of hyperglycemia

20. Any episode of symptomatic hypoglycemia during the run-in period in which symptoms were severe

21. An inability to comprehend or unwillingness to provide written informed consent in accordance with institutional and regulatory guidelines

• 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

Andrew Allegretti, M.D.

Role: STUDY_DIRECTOR

Massachusetts General Hospital

Locations

Research Site

Fresno, California, United States

Research Site

La Palma, California, United States

Research Site

Lincoln, California, United States

Research Site

Riverside, California, United States

Research Site

Sacramento, California, United States

Research Site

San Dimas, California, United States

Research Site

Monument, Colorado, United States

Research Site

Norwalk, Connecticut, United States

Research Site

Hollywood, Florida, United States

Research Site

Tampa, Florida, United States

Research Site

West Palm Beach, Florida, United States

Research Site

Paducah, Kentucky, United States

Research Site

Auburn, Maine, United States

Research Site

Rockport, Maine, United States

Research Site

Nashua, New Hampshire, United States

Research Site

The Bronx, New York, United States

Research Site

Stow, Ohio, United States

Research Site

Oklahoma City, Oklahoma, United States

Research Site

Austin, Texas, United States

Research Site

Austin, Texas, United States

Research Site

North Richland Hills, Texas, United States

Research Site

Round Rock, Texas, United States

Research Site

San Antonio, Texas, United States

Research Site

Dijon, , France

Research Site

Paris, , France

Research Site

Paris, , France

Research Site

Paris, , France

Research Site

Pierre-Bénite, , France

Research Site

Poitiers, , France

Research Site

Vénissieux, , France

Research Site

Atsugi-shi, Kanagawa, Japan

Research Site

Kamakura-shi, Kanagawa, Japan

Research Site

Kawasaki-shi, Kanagawa, Japan

Research Site

Yokohama, Kanagawa, Japan

Research Site

Yokohama, Kanagawa, Japan

Research Site

Yokohama, Kanagawa, Japan

Research Site

Kyoto, Kyoto, Japan

Research Site

Kyoto, Kyoto, Japan

Research Site

Kawagoe-shi, Saitama, Japan

Research Site

Kawaguchi-shi, Saitama, Japan

Research site

Sayama-shi, Saitama, Japan

Research Site

Hachioji-shi, Tokyo, Japan

Research Site

Hachioji-shi, Tokyo, Japan

Research Site

Minato-ku, Tokyo, Japan

Research Site

Ōta-ku, Tokyo, Japan

Research Site

Shinagawa-ku, Tokyo, Japan

Research Site

Toshima-ku, Toyko, Japan

Research Site

Alcalá de Henares, , Spain

Research Site

Alicante, , Spain

Research Site

Madrid, , Spain

Research Site

Madrid, , Spain

Research Site

Málaga, , Spain

Research Site

Málaga, , Spain

Research Site

Seville, , Spain

Research Site

Valencia, , Spain

Research Site

Valencia, , Spain

Countries

United States; France; Japan; Spain

References

Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

Reference Type: DERIVED

PMID: 38770818 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

THR-1442-C-448

Identifier Type: -

Identifier Source: org_study_id