E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type 2 diabetes mellitus (T2DM) receiving standard of care but with inadequate glycemic control and at elevated risk of cardiovascular (CV) events |
Pazienti con diabete mellito di tipo 2 (T2DM) con controllo glicemico insufficiente ed esposti a un elevato rischio di eventi cardiovascolari (CV) |
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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 | 14.1 |
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 |
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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 |
1. To assess the effect of canagliflozin compared to placebo on progression of albuminuria. |
1. Valutare l’effetto di Canagliflozin rispetto a placebo sulla progressione dell’albuminuria |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of canagliflozin compared to placebo on:
1. Regression of albuminuria
2. Estimated glomerular filtration rate (eGFR)
3. Urinary albumin/creatinine ratio |
Valutare l’effetto di Canagliflozin rispetto a placebo su:
1 regressione dell’albuminuria;
2 variazione della velocità di filtrazione glomerulare stimata (eGFR)
3 rapporto albumina/creatinina (ACR) nell’urina.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must have a diagnosis of type 2 diabetes mellitus.
2. Must have inadequate diabetes control (as defined by glycosylated hemoglobin level >=7.0% to <=10.5% at screening)
3. History or high risk of CV events.
4. Must be either not on antihyperglycemic agents (AHA) therapy, or on AHA monotherapy, or combination AHA therapy with any approved agent for the control of blood glucose levels. |
Pazienti con:
1 con diagnosi di diabete mellito di tipo 2
2 con controllo glicemico inadeguato del diabete (come definito dal livello di emoglobina fra HbA1c >7,0 e <10,5% allo screening)
3 con storia o rischio elevato di eventi cardiovascolari
4 non in terapia con agenti ipoglicemizzanti o che assumono agenti ipoglicemizzanti in monoterapia o in terapia associata con qualsiasi agente approvato per il controllo dei livelli di glucosio
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E.4 | Principal exclusion criteria |
1. History of diabetic ketoacidosis, type 1 diabetes mellitus, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy.
2. History of one or more severe hypoglycemic episode within 6 months before screening.
3. History of hereditary glucose-galactose malabsorption or primary renal glucosuria.
4. Ongoing, inadequately controlled thyroid disorder.
5. Renal disease that required treatment with immunosuppressive therapy or a history of chronic dialysis or renal transplant
6. Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening. |
1 Storia di chetoacidosi diabetica, diabete mellito di tipo 1, trapianto del pancreas o delle beta-cellule, o diabete secondario a pancreatite o pancreatectomia.
2 Storia di 1 o più episodi ipoglicemici gravi entro i 6 mesi precedenti allo screening.
3 Storia di malassorbimento ereditario del glucosio-galattosio o glicosuria renale primaria.
4 Patologia della tiroide in corso non adeguatamente controllata.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Number of participants with progression of albuminuria |
1. Numero di partecipanti con progressione dell’albuminuria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline, Week 26, 52, 78, 104, 156 |
Visita basale, settimana 26,52,78,104,156 |
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E.5.2 | Secondary end point(s) |
1. Number of participants with regression of albuminuria
2. Change in estimated glomerular filtration rate (eGFR) from baseline to the last off-treatment measurement.
3. Urinary albumin/creatinine ratio at last on-treatment visit |
1. Numero di partecipanti con regressione dell’albuminuria
2 Variazione della velocità di filtrazione glomerulare (eGFR) dal basale all’ultimo valore relativo alla fase senza trattamento,
3 Rapporto albumina/creatinina nell’urina raccolta nel corso dell’ultima visita della fase di trattamento.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline, Week 26, 52, 78, 104, 156
2. Baseline, up to Day 30 of post treatment follow-up
3. Baseline, Week 156 |
1 Visita basale, settimana 26,52,78,104,156
2 Visita basale, fino al giorno 30 del follow up di post trattamento
3 Visita basale, settimana 156
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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 | Yes |
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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 190 |
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 |
Belgium |
Brazil |
Canada |
China |
France |
Germany |
Hungary |
Italy |
Malaysia |
Mexico |
Netherlands |
New Zealand |
Poland |
Russian Federation |
Ukraine |
Czech Republic |
Korea, Republic of |
Spain |
Sweden |
Taiwan |
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
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LVLS |
ULTIMA VISITA DELL'ULTIMO PAZIENTE |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |