E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes Mellitus and Diabetic Nephropathy |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 Diabetes Mellitus and Diabetic Kidney Disease |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In subjects with T2DM, Stage 2 or 3 CKD and macroalbuminuria who are receiving standard of care, to assess the efficacy of canagliflozin relative to placebo in reducing the composite endpoint of ESKD, doubling of serum creatinine, and renal or CV death. |
|
E.2.2 | Secondary objectives of the trial |
In subjects with T2DM, Stage 2 or 3 CKD and macroalbuminuria who are receiving standard of care, to assess the efficacy of canagliflozin relative to placebo in reducing:
• the CV composite endpoint of CV death, non-fatal MI, non-fatal stroke, hospitalized congestive heart failure, and hospitalized unstable angina
• the renal composite endpoint of ESKD, doubling of serum creatinine, and renal death
• all-cause death |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-T2DM with a HbA1c ≥ 6.5% to ≤ 10.5%, with an eGFR ≥ 30 to < 90 mL/min/1.73m2
- Participants need to be on a maximum tolerated labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin
receptor blocker (ARB) for at least 4 weeks prior to randomization
- Must have an urine albumin to creatinine ratio (UACR) > 300 mg/g to ≤ 5000 mg/g |
|
E.4 | Principal exclusion criteria |
- History of diabetic ketoacidosis or type 1 diabetes mellitus
- History of hereditary glucose-galactose malabsorption or primary
renal glucosuria
- Renal disease that required treatment with immunosuppressive therapy
- Known significant liver disease
- Current or history of New York Heart Association (NYHA) Class IV heart failure
- Blood potassium level >5.5 millimole(mmol)/litre(L) during screening |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-Time to the first occurrence of an event in the primary composite
endpoint |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, up to approximately Month 66 |
|
E.5.2 | Secondary end point(s) |
-Time to the first occurrence of an event in the CV composite endpoint
-Time to the first occurrence of an event in the renal composite endpoint
-Time to all-cause death
-Time to the first occurrence of an event in the CV Composite Endpoint of
CV Death and Hospitalised Congestive Heart Failure
-Time to CV death |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, up to approximately Month 66 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 197 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Bulgaria |
Canada |
China |
Czech Republic |
France |
Germany |
Hong Kong |
Hungary |
India |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Philippines |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Taiwan |
Ukraine |
United Arab Emirates |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |