E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 Chronic kidney disease |
Diabetes Mellitus, Tipo 2 Nefropatía crónica |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes Chronic kidney disease |
Diabetes de tipo 2 Nefropatía crónica |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
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 |
To demonstrate that semaglutide delays the progression of renal impairment and lowers the risk of renal and cardiovascular mortality compared to placebo, both added to standard-of-care, in subjects with type 2 diabetes and chronic kidney disease. |
Demostrar que semaglutida retrasa la progresión de la insuficiencia renal y reduce el riesgo de mortalidad de origen renal y cardiovascular en comparación con placebo, ambos añadidos al tratamiento habitual, en sujetos con diabetes de tipo 2 y nefropatía crónica. |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of treatment with semaglutide versus placebo, both added to standard-of-care in subjects with type 2 diabetes and chronic kidney disease with regards to cardiovascular morbidity, peripheral artery disease, glycaemic control, body weight, blood pressure and safety. |
Comparar el efecto del tratamiento con semaglutida frente a un placebo, ambos añadidos al tratamiento habitual en sujetos con diabetes de tipo 2 y nefropatía crónica, en cuanto a morbilidad cardiovascular, arteriopatía periférica, control de la glucemia, peso corporal, presión arterial y seguridad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age 18 years or older at the time of signing informed consent. Japan: 20 years. - Diagnosed with type 2 diabetes mellitus - HbA1c (glycated haemoglobin) equal to or below 10% (equal to or below 86 mmol/mol) - Renal impairment defined either by: a) serum creatinine-based eGFR (estimated glomerular filtration rate) equal to or above 50 and equal to or below 75 mL/min/1.73 m^2 (chronic kidney disease - epidemiology collaboration, CKD-EPI) and UACR (urinary albumin-to-creatinine ratio) above 300 and below 5000 mg/g or b) serum creatinine-based eGFR equal to or above 25 and below 50 mL/min/1.73 m^2 (CKD-EPI) and UACR above 100 and below 5000 mg/g - Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks prior to the date of the laboratory assessments used for determination of the inclusion criteria for renal impairment and kept stable until screening. |
-Varón o mujer, de 18 años o más en el momento de firmar el consentimiento informado. Japón: 20 años -Diagnóstico de diabetes mellitus de tipo 2. -HbA1c (hemoglobina glicada)≤ 10% (≤ 86 mmol/mol). -Insuficiencia renal definida por: a)FGe basada en la creatinina sérica (tasa de filtración glomerular estimada) ≥ 50 y ≤ 75 ml/min/1,73 m2 (enfermedad renal crónica-colaboración epidemiológica, CKD-EPI) y CACO (cociente albúmina/creatinina en orina) > 300 y < 5000 mg/g o b)FGe basada en la creatinina sérica ≥ 25 y < 50 ml/min/1,73 m2 (CKD-EPI) y CACO > 100 y < 5000 mg/g. -Tratamiento con la dosis máxima nominal o tolerada de un bloqueante del sistema renina-angiotensina-aldosterona (SRAA), como un inhibidor de la enzima convertidora de la angiotensina (IECA) o un antagonista de los receptores de la angiotensina II (ARA), a menos que dicho tratamiento esté contraindicado o no se tolere. La dosis del tratamiento deberá mantenerse estable durante al menos 4 semanas antes de la fecha de las evaluaciones analíticas utilizadas para determinar los criterios de inclusión relacionados con la insuficiencia renal y mantenerse estable hasta la selección. |
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E.4 | Principal exclusion criteria |
- Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations - Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to screening - Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening - Presently classified as being in New York Heart Association (NYHA) Class IV heart failure - Planned coronary, carotid or peripheral artery revascularisation - Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal dialysis - Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination |
-Nefropatías congénitas o hereditarias, como poliquistosis renal, nefropatías autoinmunitarias, incluida glomerulonefritis, o malformaciones congénitas de las vías urinarias. -Uso de cualquier agonista del receptor del péptido glucagonoide-1 (GLP-1) en los 30 días previos a la selección. -Infarto de miocardio, ictus u hospitalización por angina de pecho inestable o accidente isquémico transitorio en los 60 días previos al día de la selección. -Insuficiencia cardíaca clasificada en la clase funcional IV según la New York Heart Association (NYHA). -Revascularización arterial coronaria, carotídea o periférica programada. -Hemodiálisis o diálisis peritoneal crónica o intermitente activa (o en los 90 días previos). -Retinopatía diabética o maculopatía no controlada y potencialmente inestable, verificada mediante una exploración del fondo de ojo realizada en los 90 días previos a la selección o en el período comprendido entre la selección y la aleatorización. La dilatación pupilar farmacológica es un requisito a menos que se utilice una cámara fotográfica digital del fondo de ojo especificada para una exploración sin dilatación |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first occurrence of a composite endpoint consisting of: Onset of persistent equal to or above 50% reduction in estimated glomerular filtration rate (eGFR) (CKD-EPI) compared with baseline, onset of persistent eGFR (CKD-EPI) below 15 mL/min/1.73 m^2, initiation of chronic renal replacement therapy (dialysis or kidney transplantation), renal death, or cardiovascular death. |
Tiempo hasta el primer episodio de un criterio de valoración combinado formado por: aparición de una reducción persistente ≥ 50% de la filtración glomerular estimada (FGe) (CKD-EPI) en comparación con el valor basal, aparición de una FGe persistente (CKD-EPI) < 15 ml/min/1,73 m2, inicio de un tratamiento de sustitución renal crónica (diálisis o trasplante de riñón), muerte de origen renal o muerte de origen cardiovascular |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomisation (week 0) to end-of-trial (up to 61 months or more) |
Desde la aleatorización (semana 0) hasta el fin de ensayo (hasta 61 meses o más) |
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E.5.2 | Secondary end point(s) |
1. Annual rate of change in eGFR (CKD-EPI) (total eGFR slope) 2. Time to first occurrence of a composite cardiovascular MACE endpoint consisting of: - Non-fatal myocardial infarction - Non-fatal stroke - CV death 3. Time to occurrence of all-cause death |
1. Tasa anual de variación de la FGe (CKD-EPI) (pendiente total de FGe) 2. Tiempo hasta el primer episodio de un criterio de valoración combinado de complicaciones cardiovasculares graves (CCG): -Infarto de miocardio no mortal - Ictus no mortal - Muerte de origen CV) 3. Tiempo hasta muerte por todas las causas |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For all secondary endpoints: From randomisation (week 0) to end-of-trial (up to 61 months or more) |
Para todos los criterios de valoración secundarios: Desde la aleatorización (semana 0) hasta el fin de ensayo (hasta 61 meses o más) |
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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 | 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 119 |
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 |
Canada |
China |
European Union |
India |
Israel |
Japan |
Malaysia |
Mexico |
Russian Federation |
South Africa |
Thailand |
Turkey |
Ukraine |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 18 |