E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes Mellitus and Diabetic Kidney Disease |
Diabetes Mellitus Tipo 2 y diagnóstico clínico de nefropatía diabética |
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E.1.1.1 | Medical condition in easily understood language |
Type II Diabetes Mellitus and Diabetic Kidney Disease |
Diabetes Mellitus Tipo 2 y diagnóstico clínico de nefropatía diabética |
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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 | 18.0 |
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. |
? Demostrar si, añadida al tratamiento estándar, finerenona es superior al placebo en retrasar la aparición del primer evento de morbimortalidad cardiovascular en sujetos con diabetes mellitus de tipo 2 y el diagnóstico clínico de nefropatía diabética. |
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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. |
-Retrasa el tiempo transcurrido hasta la primera aparición del siguiente criterio de valoración compuesto: aparición de insuficiencia renal, reducción mantenida de la filtración glomerular estimada (FGe) ? 40 % respecto al periodo basal durante al menos 4 semanas o muerte por causas renales - Retrasa el tiempo transcurrido hasta la hospitalización por cualquier causa - Retrasa el tiempo transcurrido hasta la muerte por cualquier causa - Cambio en el cociente albúmina/creatinina (CAC) en orina respecto al periodo basal hasta el mes 4 - Retrasa el tiempo transcurrido hasta la primera aparición del siguiente criterio de valoración compuesto: aparición de insuficiencia renal, reducción mantenida de la FGe ? 57 % respecto al periodo basal durante al menos 4 semanas o muerte por causas renales. |
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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) OR Persistent 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 both Starting with the Run-in Visit, subjects should be treated with only an ACEI or ARB For 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 |
- Hombres o mujeres a partir de 18 años - Sujetos con diabetes mellitus tipo 2 según la definición de la American Diabetes Association - Diagnóstico de nefropatía diabética con al menos uno de los criterios siguientes en las visitas de lavado y selección: - albuminuria elevada persistente . o - albuminuria muy elevada persistente . - Tratamiento previo durante al menos 4 semanas antes de la visita de selección bien con un inhibidor de la enzima convertidora de la angiotensina o bien con un antagonista del receptor de la angiotensina a la dosis máxima tolerada autorizada, preferiblemente sin ajustes de la dosis ni elección de otro fármaco o tratamiento. - Potasio sérico ? 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 |
- Nefropatía no diabética significativa confirmada, incluida estenosis de la arteria renal clínicamente significativa. - Hipertensión arterial no controlada (es decir, PAS media en sedestación ? 170 mm Hg, PAD en sedestación ? 110 mm Hg en la visita de lavado, o PAS media en sedestación ? 160 mm Hg, PAD en sedestación ? 100 mm Hg en la visita de selección) - Diagnóstico clínico de de insuficiencia cardiaca con fracción de eyección reducida (ICFEr) crónica y síntomas persistentes (clase II ? IV de la NYHA) en la visita de lavado (recomendación de clase 1A para antagonistas del receptor de mineralocorticoides: ARM) - Diálisis por insuficiencia renal aguda en las 12 semanas anteriores a la visita de lavado - Aloinjerto renal realizado o trasplante renal programado en los 12 meses siguientes - 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). |
Tiempo transcurrido hasta la primera aparición del criterio de valoración compuesto de muerte cardiovascular (CV) o acontecimiento CV no mortal (es decir, infarto de miocardio, ictus u hospitalización por insuficiencia cardíaca). |
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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 18 to 36 months |
Desde el día de la aleatorización (visita 1) hasta la visita de final del estudio tras la decisión de finalización del estudio, aproximadamente entre los 18 y los 36 meses. |
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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 death Time to all-cause hospitalization Time to all-cause mortality Change in UACR from baseline to Month 4 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. |
Tiempo transcurrido hasta la primera aparición del criterio de valoración compuesto: aparición de insuficiencia renal, reducción mantenida de la filtración glomerular estimada (FGe) ? 40 % respecto al periodo basal durante al menos 4 semanas o muerte por causas renal Tiempo transcurrido hasta la hospitalización por cualquier causa Tiempo transcurrido hasta la muerte por cualquier causa Cambio en el cociente albúmina/creatinina en orina respecto al periodo basal hasta el mes 4* Tiempo transcurrido hasta la primera aparición del siguiente criterio de valoración compuesto: aparición de insuficiencia renal, reducción mantenida de la FGe ? 57 % respecto al periodo basal durante al menos 4 semanas o muerte por causas renales. |
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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 months
Except endpoint*: Frombaseline / randomization to Month 4 |
Para todos los eventos: Desde aleatorización (Visita 1) hasta la visita de final del estudio tras la decisión de finalización del estudio, aproximadamente entre los 18 y los 36 meses
Excepto evento*: Desde visita basal/aleatorización hasat mes 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 | 14 |
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 | 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 |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Lithuania |
Netherlands |
New Zealand |
Norway |
Philippines |
Poland |
Portugal |
Russian Federation |
Saudi Arabia |
Singapore |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
Vietnam |
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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 |
Última visita del último sujeto |
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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 | 36 |
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 | 36 |
E.8.9.2 | In all countries concerned by the trial days | 0 |