E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 Diabetes Mellitus and Diabetic Nephropathy |
Diabete mellito di tipo 2 e nefropatia diabetica |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 Diabetes Mellitus |
Diabete mellito di tipo 2 |
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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 | 16.1 |
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. |
: Nei soggetti affetti da T2DM, malattia renale cronica (MCR) di stadio 2 o 3 e macroalbuminuria che stanno ricevendo lo standard di cura, valutare l’efficacia di canagliflozin rispetto al placebo nel ridurre l’endpoint composito costituito da malattia renale di stadio finale (end-stage kidney disease, ESKD), raddoppio della creatinina sierica e decesso cardiovascolare (CV) o renale. |
|
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 |
Nei soggetti affetti da T2DM, MRC di stadio 2 o 3 e macroalbuminuria che stanno ricevendo lo standard di cura, valutare l’efficacia di canagliflozin rispetto al placebo nel ridurre:
• l’endpoint composito CV costituito da decesso CV, infarto miocardico (IM) non fatale, ictus non fatale, ricovero per insufficienza cardiaca congestizia e ricovero per angina instabile;
• l’endpoint composito renale costituito da ESKD, raddoppio della creatinina sierica e morte renale;
• decesso correlato a qualsiasi 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 |
- T2DM con HbA1c da 6,5% a 10,5%, una eGFR da 30 a <90 ml/min/1,73m2
- soggetti che stanno ricevendo una dose giornaliera massima tollerata, secondo etichetta, di un inibitore dell'enzima di conversione dell'angiotensina
(ACEi) o di un bloccante del recettore dell’angiotensina (ARB) per almeno 4 settimane precedenti la randomizzazione
- rapporto albumina / creatinina nelle urine (UACR) da > 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
- 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 |
- Storia di chetoacidosi diabetica o diabete mellito tipo 1
- Storia di malassorbimento di glucosio-galattosio ereditaria o
glicosuria renale primaria
- Malattia renale che ha richiesto il trattamento con terpia immunosoppressiva
- Malattia epatica importante nota
- Insufficienza cardiaca di Classe IV secondo la New York Heart Association (NYHA) pregressa o in corso.
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E.5 End points |
E.5.1 | Primary end point(s) |
-Time to the first occurrence of an event in the primary composite
endpoint |
Tempo alla prima insorgenza di un evento nel l’endpoint composito primario |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, up to Month 66 |
Basale, fino al Mese 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 |
- Tempo alla prima insorgenza di un evento nell’endpoint composito cardiovascolare (CV)
- Tempo alla prima insorgenza di un evento nell’endpoint composito renale
- Tempo al decesso determinato da qualsiasi causa.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, up to Month 66 |
Basale, fino al Mese 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 | 25 |
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 |
Bulgaria |
Canada |
China |
France |
Italy |
Japan |
New Zealand |
Romania |
Argentina |
Australia |
Brazil |
Czech Republic |
Germany |
Hong Kong |
Hungary |
Korea, Republic of |
Malaysia |
Spain |
Mexico |
Philippines |
Poland |
Russian Federation |
South Africa |
Taiwan |
Ukraine |
United Kingdom |
United States |
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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 | 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 |