E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes Mellitus and Diabetic Kidney Disease |
diabete mellito di tipo 2 e con diagnosi clinica di nefropatia diabetica |
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E.1.1.1 | Medical condition in easily understood language |
Type II Diabetes Mellitus and Diabetic Kidney Disease |
diabete mellito di tipo 2 e con diagnosi clinica di nefropatia diabetica |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061835 |
E.1.2 | Term | Diabetic nephropathy |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 |
Demonstrate whether, in addition to standard of care, finerenone is superior to placebo in delaying the time to first occurrence of cardiovascular mortality and morbidity in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease. |
¿ Dimostrare se, in aggiunta allo standard di cura (SoC), finerenone sia superiore al placebo nel ritardare il tempo alla comparsa della mortalit¿ e della morbilit¿ cardiovascolare (CV) in soggetti affetti da diabete mellito di tipo 2 (T2DM) con diagnosi clinica di nefropatia diabetica (DKD) |
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E.2.2 | Secondary objectives of the trial |
¿Delays the time to first occurrence of the following composite endpoint:onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) of =40% from baseline over at least 4 weeks or renal death¿Delays the time to all-cause hospitalization¿Delays the time to all-cause mortality¿Change in UACR from baseline to Month 4¿Delays the time to first occurrence of the following composite endpoint:onset of kidney failure, a sustained decrease in eGFR of =57% from baseline over at least 4 weeks or renal death. |
Gli obiettivi secondari di questo studio sono quelli di stabilire se, in aggiunta allo SoC, finerenone in confronto a placebo: ¿ Ritarda il tempo alla comparsa del seguente endpoint composito:inizio dell¿insufficienza renale, riduzione sostenuta della filtrazione glomerulare stimata (eGFR) di >40% dal basale in almeno 4 settimane o morte renale ¿ Ritarda il tempo alla mortalit¿ per tutte le cause ¿ Ritarda il tempo all¿ospedalizzazione per tutte le cause ¿ Determina una variazione dell¿UACR dal basale al Mese 4 ¿ Ritarda il tempo che precede la comparsa del seguente endpoint composito: insufficienza renale, diminuzione costante della GFR del >57% dal basale in almeno 4 settimane o morte renale
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men or women aged 18 years and older. The lower age limit may be higher if legally required in the participating country.- Women of childbearing potential can only be included in the study if a pregnancy test is negative at the screening visit and if they agree to use adequate contraception. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: FSH levels > 40 mIU/mL and estradiol < 20 pg/mL] or have had surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy.-Subjects with type 2 diabetes mellitus as defined by the American Diabetes Association-Subjects with a clinical diagnosis of DKD based on either of the following criteria at the Run-in and Screening Visit:Persistent high albuminuria defined as UACR of = 30 mg/g (= 3.4 mg/mmol) but < 300 mg/g (< 33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR = 25 but = 90 mL/min/1.73 m2 (CKD-EPI)ORPersistent very high albuminuria defined as UACR of =300 mg/g (=33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR =60 mL/min/1.73 m2 (CKD-EPI) -Prior treatment with ACEIs and ARBs as follows:For at least 4 weeks prior to the Run-in Visit, subjects should be treated with either an ACEI or ARB, or bothStarting with the Run-in Visit, subjects should be treated with only an ACEI or ARBFor at least 4 weeks prior to the Screening Visit, subjects should be treated with the maximum tolerated labeled dose (but not below the minimal labeled dose) of only an ACEI or an ARB (not both) preferably without any adjustments to dose or choice of agent or to any other antihypertensive or antiglycemic treatment- Serum potassium = 4.8 mmol/L at both the Run-in and the Screening Visit |
• Uomini o donne =18 anni d’età • T2DM come è definito dall’American Diabetes Association • Diagnosi di DKD con almeno uno dei seguenti criteri alle visite di Run-in e di Screening: - albuminuria persistente elevata OPPURE - albuminuria persistente molto elevata • Pazienti pretrattati per almeno 4 settimane prima della Visita di Screening con ACEI o ARB alla dose massima tollerata indicata sul foglio illustrativo, preferibilmente senza aggiustamenti della dose o scelta di un farmaco o di un altro trattamento • Potassiemia =4.8 mmol/L.
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E.4 | Principal exclusion criteria |
- Known significant non-diabetic renal disease, including clinically relevant renal artery stenosis- Uncontrolled arterial hypertension with mean sitting systolic blood pressure (SBP) = 170 mmHg or mean sitting diastolic blood pressure (DBP) = 110 mmHg at the Run-in Visit or mean sitting SBP =160 mmHg or mean sitting DBP =100 mmHg at the Screening Visit- Clinical diagnosis of chronic HFrEF and persistent symptoms (NYHA class II – IV) at Run in visit (class 1A recommendation for MRAs) - Dialysis for acute renal failure within 12 weeks of Run-in visit- Renal allograft in place or scheduled kidney transplant within next 12 months from the Run-in visit - HbA1c > 12% (> 108 mmol/mol) at the Run-in Visit or Screening Visit |
• Nefropatia non-diabetica significativa confermata, compresa una stenosi dell’arteria renale clinicamente rilevante • Ipertensione arteriosa incontrollata (cioè pressione sistolica media in posizione seduta =170 mmHg, pressione diastolica in posizione seduta =110 mmHg alla visita di run-in, oppure pressione sistolica media in posizione seduta =160 mmHg, pressione diastolica in posizione seduta =100 mmHg allo screening) • Diagnosi clinica di HFrEF cronica e sintomi persistenti (classe II-IV secondo la NYHA) alla visita di run-in (classe 1A raccomandazione per MRA) • Dialisi per l’insufficienza renale acuta entro 12 settimane dalla visita di run-in • Allotrapianto di rene effettuato o programmato entro i prossimi 12 mesi • HbA1c > 12%.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first occurrence of the composite endpoint of CV death or non-fatal CV event (i.e. myocardial infarction, stroke, or hospitalization for HF). |
Tempo alla prima comparsa dell’endpoint composito di morte cardiovascolare o di evento cardiovascolare non fatale (cioè infarto miocardico, ictus o ricovero in ospedale per scompenso cardiaco) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization (Visit 1) until the end of study following the study termination decision, approximately from 7 to 51 months |
Dalla randomizzazione (Visita 1) fino a fine studio secondo le decisioni di conclusione dello studio, circa da 7 a 51 mesi |
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E.5.2 | Secondary end point(s) |
Time to first occurrence of the following composite endpoint:onset of kidney failure, a sustained decrease of eGFR = 40% from baseline over at least 4 weeks or renal deathTime to all-cause hospitalization Time to all-cause mortalityChange in UACR from baseline to Month 4Time to first occurrence of the following composite endpoint: onset of kidney failure, a sustained decrease in eGFR of = 57% from baseline over at least 4 weeks or renal death. |
Tempo alla prima comparsa del seguente endpoint composito: insorgenza di insufficienza renale, diminuzione sostenuta di eGFR = 40% dal basale oltre almeno 4 settimane o morte renale Tempo ime to all-cause hospitalization Time to ad ogni causa di morte Cambiamento di UACR dal basale al mese 4
Tempo alla prima comparsa del seguente endpoint composite endpoint: insorgenza di insufficienza renale, diminuzione sostenuta di eGFR = 57% dal basale oltre almeno 4 settimane o morte renale |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For all endpoints: From randomization (Visit 1) until the end of study following the study termination decision, approximately from 18 to 36 monthsExcept endpoint*:Frombaseline / randomization to Month 4 |
For all endpoints: From randomization (Visit 1) until the end of study following the study termination decision, approximately from 18 to 36 monthsExcept endpoint*:Frombaseline / randomization to Month 4 |
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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 | Yes |
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) | 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 | 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 | 21 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 300 |
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 | Information not present in EudraCT |
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 |
Australia |
Brazil |
Canada |
Chile |
China |
Colombia |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Philippines |
Russian Federation |
Saudi Arabia |
Singapore |
South Africa |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
Vietnam |
Austria |
Belgium |
Bulgaria |
Denmark |
Finland |
France |
Greece |
Hungary |
Ireland |
Italy |
Lithuania |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
Argentina |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 53 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 53 |
E.8.9.2 | In all countries concerned by the trial days | 0 |