A clinical trial in patients with type II diabetes with increased risk of cardiovascular events (incidents that may cause damage to the heart muscle), to study how well a person’s diabetes is controlled over a 2-3 month period with bexagliflozin, by measuring blood sugar levels using a HbA1c test, and to determine safety by assessing occurrence of cardiovascular events.
- Conditions
- Type II diabetesMedDRA version: 21.1Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2015-001760-19-NL
- Lead Sponsor
- Theracos Sub, LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1650
The study population will include:
1. Male or female adult subjects with an age =40 years
2. Subjects with a diagnosis of T2DM
3. Subjects with HbA1c values of 7.0 – 11%, inclusive
4. Subjects with fasting plasma glucose (FPG) = 300 mg/dL at screening
5. Subjects who have a regimen for treatment of T2DM that has been stable for the past 3 months. A stable regimen is defined as: no changes in dose or frequency of OHAs or GLP-1 agonists, or < 20% variability in total daily insulin dose.
6. Subjects who present with at least one of the following 3 histories:
Group 1: A history of atherosclerotic vascular disease as defined by one or more of the following:
a) myocardial infarction (MI) or ischemic (non-hemorrhagic) stroke
> 3 months but = 5 years prior to screening or
b) documented history of coronary, carotid, or peripheral arterial revascularization (coronary artery bypass grafting must have occurred = 5 years prior to screening)
Group 2: A history of NYHA class II or class III heart failure (Appendix 4) at the time of screening. A history of heart failure is defined as:
• documented left ventricular ejection fraction (LVEF) = 40% and no subsequent LVEF > 40% within 6 months of screening, or
• (i) an NT-proBNP >300 pg/mL and no evidence of atrial fibrillation/flutter (AF) at the time of the screening ECG or an NT-proBNP >900 pg/mL and evidence of AF at the time of the screening ECG and (ii) either (a) structural heart disease documented by report of left atrial enlargement or left ventricular hypertrophy, or (b) exhibiting symptom(s) of HF requiring treatment with diuretic(s) for at least 30 days prior to screening.
Group 3: Age = 55 years with 2 or more of the following:
a) diabetes duration of = 10 years,
b) uncontrolled hypertension defined as SBP > 140 mmHg despite 3 or more anti-hypertensive medications
c) current smoking,
d) urine albumin:creatinine ratio (UACR) > 30 mg/g,
e) eGFR of 45 to 60 mL/min/1.73 m2, or
f) HDL < 1 mmol/L (38 mg/dL)
7. Female subjects of childbearing potential who are willing to use an adequate method of contraception and to not become pregnant for the duration of the study. Adequate contraceptive measures include, but are not limited to, oral contraceptives, intrauterine devices, Depo-Provera, Norplant, hormonal contraceptive implants, bilateral tubal ligation, partner with vasectomy, condom or diaphragm plus contraceptive sponge, foam, or jelly, and abstinence
8. Subjects who are willing and able to return for all clinic visits and to complete all study required procedures, including self-monitored blood glucose (SMBG) measurement, and take run-in medication, missing no more than one dose due to non-compliance.
9. Subjects who receive anti-hypertensive medications at a stable dosage for = 2 weeks prior to randomization
10. Subjects who receive lipid modifying therapy on a stable regimen for 6 weeks prior to randomization
11. Subjects who have seated SBP < 170 mmHg and DBP < 110 mmHg at screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 825
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 825
Patients who exhibit any of the following characteristics will be excluded from the study.
1. Diagnosis of type 1 diabetes mellitus or maturity–onset/diabetes of the young (MODY)
2. Hemoglobinopathy that affects HbA1c measurement
3. Frequent symptomatic hypoglycemia (greater than one episode per week on average)
4. Genitourinary tract infection within 6 weeks of screening or history of = 3 genitourinary infections requiring treatment within the last 6 months
5. Cancer, active or in remission for < 3 years (Non-melanoma skin cancer or basal cell carcinoma or carcinoma in situ of the cervix will not be grounds for exclusion)
6. 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 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
8. History of MI, stroke or hospitalization for heart failure in the prior 3 months
9. Evidence of NYHA class IV heart failure at screening or randomization
10. Presently scheduled for percutaneous coronary intervention, coronary artery bypass grafting or any surgical procedure
11. Previous treatment with bexagliflozin or EGT0001474
12. Currently or within 3 months of taking any SGLT2 inhibitors
13. 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
14. Prior renal transplantation or evidence of nephrotic syndrome, defined as a urine albumin: creatinine ratio (UACR) > 2000 mg/g, at screening
15. Implantation of a cardiac resynchronization therapy device within 3 months prior to screening or intent to implant a cardiac resynchronization therapy (CRT) within 6 months following screening
16. Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within 12 months prior to screening
17. Symptomatic bradycardia or second or third degree atrioventricular block without a pacemaker
18. eGFR, as calculated by the modification of diet in renal disease study equation (MDRD), < 45 mL/min/1.73 m2 or requiring dialysis
19. Pregnant or nursing
20. Currently participating in another interventional trial.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method