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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 July 2021
• Main ID: NCT02836873
• Date of registration: 14/07/2016
• Prospective Registration: Yes
• Primary sponsor: Theracos
• Public title: Safety and Efficacy of Bexagliflozin in Type 2 Diabetes Mellitus Patients With Moderate Renal Impairment
• Scientific title: A Double Blind Placebo Controlled Study to Evaluate the Effect of Bexagliflozin Tablets on Hemoglobin A1c in Patients With Type 2 Diabetes Mellitus and Moderate Renal Impairment
• Date of first enrolment: September 23, 2016
• Target sample size: 312
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02836873
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

France, Japan, Spain, United States

Contacts

• Name: Andrew Allegretti, M.D.
• Affiliation: Massachusetts General Hospital

Key inclusion & exclusion criteria

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 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).

9.3.2 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



Age minimum: 20 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus

Intervention(s)

Drug: Placebo

Drug: Bexagliflozin

Primary Outcome(s)

Change From Baseline in HbA1c at 24 Weeks [Time Frame: 24 weeks]

Secondary Outcome(s)

Change From Baseline in HbA1c in Subjects With Stage 3a CKD (eGFR 45 to 59 mL/Min/1.73 m2) at Week 24 [Time Frame: 24 weeks]

Change From Baseline in HbA1c in Subjects With Stage 3b CKD (eGFR 30 to 44 mL/Min/1.73 m2) at Week 24 [Time Frame: 24 weeks]

Change in Body Weight From Baseline to Week 24 in Subjects With a BMI = 25 kg/m2 [Time Frame: 24 weeks]

Change From Baseline in Systolic Blood Pressure (SBP) in Subjects With Baseline SBP = 130 mm Hg at Week 24 [Time Frame: 24 weeks]

Secondary ID(s)

THR-1442-C-448

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/04/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02836873