diabetes Diabetes mellitus
Conditions
Interventions
Upon successful completion of the initial screening, all potentially eligible
individuals will enter a 2-week run in period, during which they will receive
single-blind placebo tablets (to be admini
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria at Screening Visit *Man or woman with a diagnosis of T2DM with HbA1c level > or or or 140 mmHg on at least one blood pressure-lowering treatment, current daily cigarette smoker, documented micro- or macro¬-albuminuria, or documented HDL-C of 80% of their single-blind placebo tablets during the 2 week run-in period at Day 1 to be eligible for randomization.
Exclusion criteria
Exclusion criteria: Diabetes-Related/Metabolic *History of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy *On an AHA and not on a stable regimen (ie, agents and doses) for at least 8 weeks before the screening visit Note: a stable dose of insulin is defined as no change in the insulin regimen (ie, type[s] of insulin) and 270 mg/dL (>15 mmol/L) at Baseline/Day 1 *For patients on a sulphonylurea agent or on insulin: fasting fingerstick glucose at home or investigational site 270 mg/dL (>15 mmol/L) may have their AHA regimen adjusted, and be rescreened once on a stable regimen for at least 8 weeks. *History of one or more severe hypoglycemic episode within 6 months before screening *History of hereditary glucose-galactose malabsorption or primary renal glucosuria *Run-in visit thyroid stimulating hormone [TSH] value that is 10 mIU/L. Subjects taking a thyroxine supplementation for thyroid disorder should be on a stable dose for at least 6 weeks before baseline Renal/Cardiovascular *Renal disease that required treatment with immunosuppressive therapy or a history of chronic dialysis or renal transplant. Note: subjects with a history of treated childhood renal disease, without sequelae, may participate *Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening, or a planned revascularization procedure, or history of New York Heart Association (NYHA) Class IV cardiac disease; refer to Attachment 3, New York Heart Association Classification of Cardiac Disease, for a description of the classes *Findings on 12-lead ECG that would require urgent diagnostic evaluation or intervention (eg, new clinically important arrhythmia or conduction disturbance) Gastrointestinal *History of hepatitis B surface antigen or hepatitis C antibody positive (unless associated with documented persistently stable/normal range aspartate aminotransferase [AST] and ALT levels), or other clinically active liver disease *Any history of or planned bariatric surgery Laboratory *Estimated glomerular filtration rate (eGFR) or = 1.5 mg/dL (133 *mol/L) for men and > or = 1.4 mg/dL (124 µmol/L) for women, at screening; or eGFR 2.0 times the ULN or total bilirubin >1.5 times the ULN, at screening, unless in the opinion of the investigator and as agreed upon by the sponsor*s medical officer, the findings are consistent with Gilbert*s disease Other conditions *History of malignancy within 5 years before screening (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator, with concurrence with the sponsor*s medi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The hypothesis of CV risk reduction for canagliflozin will be evaluated based upon the events in the CV composite endpoint of MACE (CV death, nonfatal MI, nonfatal stroke). An independent Endpoint Adjudication Committee will assess all events that could potentially be in the specified CV endpoint and only those events where the committee, using methodology and definitions defined in the committee*s charter, determines a specified endpoint has occurred will be included in the primary analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Efficacy Endpoints: HbA1c, FPG, systolic and diastolic blood pressure, body weight, albuminuria, eGFR, and fasting plasma lipids. The change from baseline in HbA1c, FPG, systolic and diastolic blood pressure, body weight, albuminuria, and eGFR and percent change in fasting plasma lipids will be evaluated. Urinary albumin/creatinine ratio (from first morning void) will be measured and classified. The proportion of subjects with progression of albuminuria will be evaluated. Measurements to assess HOMA B and the proinsulin/insulin ratio will be collected in a subset of subjects of approximately 1,200 subjects (at designated sites) who are not receiving insulin at baseline. Safety and tolerability will be evaluated on the basis of the overall incidence of adverse events and incidence of specific adverse events, discontinuation rate due to adverse experiences, incidence of CV events, incidence of clinically important changes in clinical laboratory tests, ECGs, vital signs, physical examination, and body weight. | — |
Countries
Netherlands
Outcome results
None listed