E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes Mellitus and Diabetic Kidney Disease |
Diabetes mellitus tipo 2 y enfermedad renal diabética |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 Diabetes Mellitus |
Diabetes mellitus tipo 2 |
|
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 | 17.0 |
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. |
En sujetos con DM2, ERC en estadio 2 o 3 y macroalbuminuria que están recibiendo un tratamiento estándar, para evaluar la eficacia de canagliflozina en relación con un placebo en la reducción del criterio de valoración combinado de insuficiencia renal terminal (IRT), duplicación de la creatinina sérica y muerte renal o cardiovascular (CV) |
|
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 |
En sujetos con DM2, ERC en estadio 2 o 3 y macroalbuminuria que están recibiendo un tratamiento estándar, para evaluar la eficacia de canagliflozina en relación con un placebo en la reducción de: ? el criterio de valoración combinado de muerte CV, infarto de miocardio (IM) no mortal, ictus no mortal, hospitalización por insuficiencia cardíaca congestiva, hospitalización por angina inestable ? el criterio de valoración renal combinado de IRT, duplicación de la creatinina sérica y muerte renal ? muerte por cualquier causa |
|
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 |
- DM2 con HbA1c de ? 6,5 % a ? 10,5 % con TFGe de ? 30 a < 90 ml/min/1,73 m2 - Los sujetos deben tener una dosis diaria máxima tolerada indicada de IECA o BRA durante al menos 4 semanas antes de la aleatorización. - Deben tener un cociente de albúmina a creatinina en orina (CACO) de > 300 mg/g a ? 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 - History of hyperkalemia requiring treatment, or blood potassium level >5.5 mmol/L at baseline - Use of mineralocorticoid receptor antagonists (MRA) or a direct renin inhibitor (DRI) - 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 |
- Antecedentes de cetoacidosis diabética o diabetes mellitus tipo 1 (DM1). - Antecedentes de mala absorción de glucosa-galactosa hereditaria o glucosuria renal primaria. - Antecedentes de hiperpotasemia que requiere tratamiento o un nivel de potasio en la sangre > 5,5 mmol/l al inicio del estudio - El uso de antagonistas de los receptores de mineralocorticoides (ARM) o un inhibidor directo de la renina (IDR) - Enfermedad renal que requiere tratamiento inmunosupresor - Enfermedad hepática significativa conocida - Antecedentes de insuficiencia cardíaca o en la actualidad de clase IV de la enfermedad cardíaca de la Asociación del corazón de Nueva York (New York Heart Association, NYHA) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-Time to the first occurrence of an event in the primary composite endpoint |
- Tiempo hasta la primera aparición de un evento en el criterio de valoración principal combinado |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, up to Month 66 |
Basal, hasta mes 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 |
- El tiempo hasta la primera incidencia de los acontecimientos en el criterio de valoracion CV - El tiempo hasta la primera incidencia de los acontecimientos en el criterio de valoración renal - El tiempo hasta la muerte por cualquier causa |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, up to Month 66 |
Basal, hasta mes 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 | Yes |
E.8.1.7.1 | Other trial design description |
Single-blind run-in; Event driven |
|
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 | 22 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 196 |
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 |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Philippines |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Taiwan |
Ukraine |
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
|
LVLS |
Ultima visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |