Health Condition 1: E115- Type 2 diabetes mellitus with circulatory complications Health Condition 2: null- Type 2 Diabetes, Cardiovascular Risk Factor and moderately impaired renal function
Conditions
Interventions
Intervention1: Sotagliflozin 200 mg tablet: Total Duration of Therapy - Approximately 27 to 51 months (per patient)
Frequency of Therapy- Once Daily
Control Intervention1: Placebo: 1 tablet
Sponsors
Lexicon Pharmaceuticals Inc
Covance India Pharmaceutical Services Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. Type 2 diabetes with HbA1c >=7% (53 mmol/mol) at Screening (central laboratory) 3. Estimated glomerular filtration rate >=25 and 4. Patients either:Age >=18 years with at least 1 (one) of the major CV risk factors listed below OR In the absence of a major CV risk factor, age >=55 years with at least 2 (two) of the minor CV risk factors listed below In order to be considered eligible to participate in the study, patients must meet ALL 4 (four) of the mandatory criteria. Patients can be eligible if they have both major and minor CV risk factors, as long as 1 of the 2 conditions in Inclusion Criterion Number 4 is met Major CV risk factors (at least 1 criterion to fulfill Inclusion Criterion Number 4) A-Hospitalization for HF during previous 2 years B-Ejection fraction (EF) Documented within the past year by previous imaging modality (such as echocardiogram, MUltiple Gated Acquisition (MUGA) scan, Magnetic Resonance Imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), left ventricular (LV) angiography) Note: An echocardiogram to assess EF at the time of Screening MUST be performed in all patients if an assessment of EF has not been documented within 1 year prior to Screening C-Diagnosis of left ventricular hypertrophy By either electrocardiogram (ECG) or echocardiogram D-Coronary artery calcium (CAC) score >=300 Agatston Unit, Documented by coronary artery CT scan Note: a coronary artery CT scan MAY be performed to measure the CAC score if required for eligibility if not previously documented E-N-terminal pro-B-type natriuretic peptide >=400 pg/mL (47 pmol/L) At Screening, based on central laboratory F-High-sensitivity troponin T >15.0 pg/mL (0.015 μg/L) for men and >10.0 pg/mL (0.010 μg/L) for women During Screening period, based on central laboratory G-High-sensitivity C-reactive protein >3 mg/L (28.6 nmol/L) At Screening, based on central laboratory, if the Investigator does not consider the elevation to be due to an acute inflammatory condition (eg, acute infection) H-Urinary albumin-to-creatinine ratio >=300 mg/g (34 mg/mmol)At Screening, based on central laboratory Minor CV risk factors (if no major CV risk factors, at least 2 criteria to fulfill Inclusion Criterion Number 4) I). Body mass index >=35 kg/m2 at Screening J). Dyslipidemia despite maximally-tolerated statin therapy:  Low-density lipoprotein cholesterol >130 mg/dL ( >3.36 mmol/L)  Or  High-density lipoprotein cholesterol Based on the last measured and documented laboratory measurement in the previous 6 months K). Currently smoking tobacco Consumes an average of at least 1 cigarette, pipe, or cigar per day, at Screening L). Coronary artery calcium score >100 and Documented by coronary artery CT scan Note: a coronary artery CT scan MAY be performed to measure the CAC score if required for eligibility if not previously documented M). Urinary albumin-to-creatinine ratio >=30 mg/g and <300 mg/g (3 and 34 mg/mmol) <br/
Exclusion criteria
Exclusion criteria: 1. History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 3 months prior to the Screening Visit or between Screening and Randomization 2. Antihyperglycemic treatment (if applicable) has not been stable in the 12 weeks prior to Screening or between Screening and Randomization, in the opinion of the Investigator 3. Patients who are planning to start a sodium-glucose linked transporter-2 (SGLT2) inhibitor (other than study drug) during the study. This includes patients who, in the opinion of the Investigator, based on their comorbid profile, are likely to receive an SGLT2 inhibitor (other than study drug) during the study. 4. Any SGLT2 inhibitor 5. Lower extremity complications (such as skin ulcers, infection, osteomyelitis, and gangrene) identified during the Screening period, and still requiring treatment at Randomization 6. Any allergic reaction to any SGLT2 inhibitor or sotagliflozin 7. Blood pressure >=180 mmHg (systolic) or >=110 mmHg (diastolic) at both the Screening and Randomization Visits 8. Hospitalization for hypertensive emergency within 3 months prior to Randomization 9. End-stage HF: requiring LV assist device, intra-aortic balloon pump (IABP), or any type of mechanical support at the time of Screening 10. Planned coronary revascularization procedures, electrophysiologic device implantation, cardiac mechanical support implantation, or other cardiac surgery after Randomization 11. History of dialysis within 1 year prior to Randomization 12. History of solid organ transplant 13. Serum creatinine altering drugs 14. Clofibrate, fenofibrate, dronedarone, or ranolazine treatment that has not been at a stable dose in the 30 daysprior to Screening or between Screening and Randomization or a dose adjustment is expected during the study based on the judgement of the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to the first occurrence of any of the following clinical events: Â-Cardiovascular death Â-Non-fatal MI Â-Non-fatal stroke Â-Hospitalization for heart failureTimepoint: Baseline to approximately 51 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to the first occurrence of any of the following clinical events in patients with Baseline eGFR â?¥30 mL/min/1.73 m2: Â-Sustained â?¥50% decrease in eGFR from Baseline (for â?¥30 days) Â-Chronic dialysis Â-Renal transplant Â-Sustained eGFR 15mL/min/1.73 m2 (for â?¥30 days)Timepoint: Baseline to approximately 51 months | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czech Republic, Denmark, Estonia, France, Georgia, Germany, Greece, Guatemala, Hungary, India, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Portugal, Republic of Korea, Romania, Russian Federation, Serbia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, The former Yugoslav Republic of Macedonia, Turkey, Ukraine, United Kingdom, United States of America
Contacts
Public ContactDr Shekhar Dawkhar
Covance India Pharmaceutical Services Private Limited
Outcome results
None listed