diabetes Diabetes mellitus
Conditions
Interventions
Upon successful completion of screening, all potentially eligible individuals
will enter a 2-week run-in
period, during which they will receive single-blind placebo capsules (one
capsule to be taken
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Man or woman with a diagnosis of T2DM with HbA1c level * 7.0% to * 10.5% at screening and be either (1) not currently on AHA therapy or (2) on AHA monotherapy or combination therapy with any approved agent: eg, sulfonylurea, metformin, pioglitazone, alpha-glucosidase inhibitor, GLP-1 analogue, DPP-4 inhibitor, or insulin.;- History or high risk of CV events defined on the basis of either: Age *30 years with documented symptomatic atherosclerotic CV events: including stroke; MI; hospital admission for unstable angina; coronary artery bypass graft; percutaneous coronary intervention (with or without stenting); peripheral revascularization (angioplasty or surgery); symptomatic with documented hemodynamically-significant carotid or peripheral vascular disease; or amputation secondary to vascular disease. 2) age * 50 years with 2 or more of the following risk factors determined at the screening visit: duration of T2DM of 10 years or more, systolic blood pressure >140 mmHg (average of 3 readings) recorded at the Screening Visit, while the subject is on at least one blood pressure-lowering treatment, current daily cigarette smoker, documented micro- or macroalbuminuria (see Section 3.2, Study Design Rationale, for definition) within one year of screening, or documented HDL-C of 45 years of age with amenorrhea for at least 18 months, or o >45 years of age with amenorrhea for at least 6 months and less than 18 months and a known serum follicle stimulating hormone (FSH) level >40 IU/L, or o surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal occlusion), or otherwise be incapable of pregnancy, or o heterosexually active and practicing a highly effective method of birth control, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization, consistent with local regulations regarding use of birth control methods for subjects participating in clinical trials, for the duration of their participation in the study, or o not heterosexually active. Note: subjects who are not heterosexually active at screening must agree to utilize a highly effective method of birth control if they become heterosexually active during their participation in the study.;- Women of childbearing potential (ie, those subjects who do not meet the postmenopausal definition above, regardless of age) must have a negative urine pregnancy test at baseline (Day 1) and at screening if required by local regulations (Note: a serum pre
Exclusion criteria
Exclusion criteria: Potential subjects who meet any of the following criteria will be excluded from participating in the study:;Diabetes-Related/Metabolic - History of diabetic ketoacidosis, T1DM, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy - History of one or more severe hypoglycemic episodes within 6 months before screening Note: a severe hypoglycemic episode is defined as an event that requires the help of another person. - History of hereditary glucose-galactose malabsorption or primary renal glucosuria - Ongoing, inadequately controlled thyroid disorder Note: subjects on thyroid hormone replacement therapy must be on a stable dose for at least 6 weeks before Day 1.;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 (The Criteria Committee of the New York Heart Association). - Known ECG findings within 3 months before screening that would require urgent diagnostic evaluation or intervention (eg, new clinically important arrhythmia or conduction disturbance);Gastrointestinal - Known history of hepatitis B surface antigen or hepatitis C antibody positive (unless known to be associated with documented persistently stable/normal range aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels), or other clinically active liver disease - Any history of or planned bariatric surgery;Laboratory - eGFR 2.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN, 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 medical monitor, is considered cured with minimal risk of recurrence) - History of human immunodeficiency virus (HIV) antibody positive - Subject has a current clinically important hematological disorder (eg, symptomatic anemia, proliferative bone marrow disorder, thrombocytopenia) - Investigator*s assessment that the subject*s life expectancy is less than 1 year, or any condition that in the opinion of the investigator would make participation not in the best interest of the subject, or could prevent, limit, or confound the protocol-specified safety or efficacy assessments - Major surgery (ie, requiring general anesthesia) within 3 months of the screening visit or any surgery planned during the subject*s expected participation in the study (except minor surgery, ie, outpatient surgery under local anesthesia) - Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or prevent the subject from meeting or p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression is the development of microalbuminuria or macroalbuminuria in a subject with baseline normoalbuminuria or the development of macroalbuminuria in a subject with baseline microalbuminuria, accompanied by an ACR value increase of greater than or equal to 30% from baseline. The primary outcome is progression of albuminuria (as defined above). If the ACR at a visit meets the definition of progression described above, a repeat ACR collection approximately 1 to 2 months later (or sooner under unusual circumstances, eg, subject is stopping study drug) must confirm progression of albuminuria (ie, confirmed progression). If the last on-treatment value meets the definition of progression and no repeat ACR collection can be made, the subject will also be deemed to have progressed. ACR assessments will be based upon values obtained from first morning void urines analyzed by the central laboratory. In this study, duplicate urine specimens will be collected for all ACR measurements. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary outcomes are: * Regression of albuminuria is the development of normoalbuminuria in a subject with baseline microalbuminuria or macroalbuminuria or the development of microalbuminuria in a subject with baseline macroalbuminuria, accompanied by a decrease in the urinary ACR value of greater than or equal to 30% from baseline. If the ACR at a visit meets the definition of regression described above, a repeat on-treatment ACR collection approximately 1 to 2 months later (or sooner under unusual circumstances, eg, subject is stopping study drug), must confirm regression of albuminuria (ie, confirmed regression). If the last on-treatment value meets the definition of regression and no repeat ACR collection can be made, the subject will also be deemed to have regressed. * Change in eGFR from baseline to the last off-treatment value done approximately 30 days post study drug discontinuation. * Urinary albumin/creatinine ratio at last on-treatment visit. Safety outcomes The data from this study will be combined with the data from another large-scale study of the effects of canagliflozin compared to placebo (CANVAS) in a pre-specified meta-analysis of cardiovascular safety outcomes to satisfy the US FDA Post Marketing Requirements. | — |
Countries
Netherlands
Outcome results
None listed