Type II diabetes MedDRA version: 20.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Product Name: Bexagliflozin Tablets
Product Code: THR-1442
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Bexagliflozin
CA
Sponsors
Theracos Sub, LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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 wh
Exclusion criteria
Exclusion criteria: 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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The Primary endpoint will be determined at baseline and at 24 weeks with supportive additional data for the model provided at 6 and 12 weeks.; Main Objective: The primary efficacy objective of this trial is to evaluate the placebo-adjusted change in HbA1c from baseline after 24 weeks of exposure to bexagliflozin in type 2 diabetic subjects with increased risk of cardiovascular adverse events. The primary safety objective of this study is the contribution of at least 134 major adverse cardiovascular events (MACE+) to an eventual meta-analysis that is intended to exclude a hazard ratio of 1.8 or greater for subjects exposed to bexagliflozin compared to subjects exposed to placebo. MACE+ is defined as cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for unstable angina. An additional objective is the evaluation of the safety of exposure to bexagliflozin for a minimum of 52 weeks in a treatment population that is at elevated risk for major adverse cardiovascular events. ; Secondary Objective: Efficacy objectives: • To evaluate the effect of bexagliflozin compared to placebo on the change in HbA1c from baseline to week 24 in randomized subjects who have been prescribed insulin to control their diabetes • To evaluate the effect of bexagliflozin on the change in body weight from baseline to week 48 in randomized subjects with a BMI = 25 kg/m2 compared to placebo • To evaluate the effect of bexagliflozin on the change in systolic blood pressure from baseline to week 24 in subjects with baseline systolic blood pressure = 140 mmHg compared to placebo • To assess the effect of bexagliflozin treatment on the change in HbA1c versus placebo over time • To evaluate the effect of bexagliflozin treatment on the chan | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoints include: •Change in HbA1c from baseline to week 24 in randomized subjects who have been prescribed insulin to control their diabetes • Change in body weight from baseline to week 48 in subjects with a BMI = 25 kg/m2 • Change in SBP from baseline to week 24 in subjects with baseline systolic blood pressure = 140 mmHg The exploratory secondary efficacy endpoints include: • Change from baseline in HbA1c over time • Change from baseline in FPG over time • Change from baseline in body weight over time • Change from baseline in SBP over time • Requirement of additional anti-diabetic medications, including insulin; and time to first use of additional anti-diabetic medication • Requirement of reduced anti-diabetic medications, including insulin dose over time • Hospitalization for heart failure in all subjects and in subjects with a history of heart failure • Time to hospitalization for heart failure in subjects in all subjects and in subjects with a history of heart failure The safety endpoints include: • Time to a 5-point composite adjudicated endpoint of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, or coronary revascularization • Time-to a 6-point composite adjudicated endpoint of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure, and coronary revascularization; and time to onset of event • Time to individual events including all-cause mortality, CV death, non-fatal MI, non-fatal stroke, transient ischemic attack, hospitalization for unstable angina, hospitalization for heart failure, and coronary revascularization; and time to onset | — |
Countries
Canada, Czech Republic, Denmark, Germany, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Taiwan, United States
Contacts
Public ContactProgram Management
Translational Medicine Group
Outcome results
None listed