E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus Chronic kidney disease |
Diabetes mellitus tipo 2 Enfermedad renal crónica |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes mellitus Chronic kidney disease |
Diabetes mellitus tipo 2 Enfermedad renal 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 | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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.1.3 | 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, when compared to placebo in patients with type 2 diabètes (T2D), cardiovascular (CV) risk factors, and moderately impaired renal function,sotagliflozin: -Does not increase the risk of cardiovascular events including death from cardiovascular disease, non-fatal heart attack and non-fatal stroke; -Reduces the risk of death from CV disease or hospitalization for heart failure. |
Demostrar que, en comparación con el placebo en pacientes con diabetes tipo 2 (DT2), factores de riesgo cardiovascular (CV) y función renal moderadamente reducida, sotagliflozina: - No es inferior al placebo en el criterio de valoración compuesto de muerte por causas CV, infarto de miocardio (IM) no mortal o accidente cerebrovascular no mortal (eventos CV adversos mayores [MACE] de 3 puntos) - Reduce el criterio de valoración compuesto de muerte por causas CV u hospitalización por insuficiencia cardiaca (HIC) |
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E.2.2 | Secondary objectives of the trial |
-To demonstrate that, when compared to placebo in patients with T2D, CV risk factors, and moderately impaired renal function, sotagliflozin: -Reduces cardiovascular events including death from cardiovascular disease, non-fatal heart attack and non-fatal stroke; -Reduces risk of progression of kidney disease; -Reduces cardiovascular events including death from cardiovascular disease and emergency treatment for heart failure; -Reduces death from cardiovascular disease; -Reduces death from any cause. -To assess the safety and tolerability of sotagliflozin. |
Demostrar que, en comparación con el placebo en pacientes con DT2, factores de riesgo CV y función renal moderadamente reducida, sotagliflozina: - Reduce eventos cardiovasculares incluyendo muerte por enfermedad cardiovascular, ataque cardíaco no fatal y accidente cerebrovascular no fatal; - Reduce el riesgo de progresión de la enfermedad renal; - Reduce eventos cardiovasculares incluyendo muerte por enfermedad cardiovascular y tratamiento de emergencia para insuficiencia cardíaca; - Reduce la muerte por enfermedad cardiovascular; - Reduce la muerte por cualquier causa. - Evaluar la seguridad y tolerabilidad de la sotagliflozina. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To compare sotagliflozin versus placebo with respect to changes in bone mineral density (BMD) in patients with T2D, CV risk factors, and moderately impaired renal function. |
Comparar la sotagliflozina versus placebo con respecto a los cambios en la densidad mineral ósea (DMO) en pacientes con DT2, factores de riesgo CV y función renal moderada. |
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E.3 | Principal inclusion criteria |
-Type 2 Diabetes Mellitus with glycosylated hemoglobin (HbA1c) ≥ 7%. -Estimated glomerular filtration rate (eGFR) ≥ 25 and ≤ 60 mL/min/1.73 m2. -Age 18 years or older with at least one major cardiovascular risk factor or age 55 years or older with at least two minor cardiovascular risk factors. -Signed written informed consent.. |
- Diabetes tipo 2 con HbA1c superior o igual a 7 % - Tasa de filtración glomerular estimada superior o igual a 25 y inferior o igual a 60 ml/min/1,73 m2 - Edad ≥18 años, con al menos 1 (uno) de los factores de riesgo CV principales o de edad superior o igual a 55 años, con al menos 2 (dos) de los factores de riesgo CV secundarios - Consentimiento informado por escrito firmado |
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E.4 | Principal exclusion criteria |
-Antihyperglycemic treatment has not been stable within 12 weeks prior to screening. -Planned coronary procedure or surgery after randomization. -Lower extremity complications (such as skin ulcer, infection, osteomyelitis, and gangrene) identified during screening and requiring treatment at randomization. -Planning to start a sodium-glucose linked transporter-2 (SGLT2) inhibitor during the study. |
- Tratamiento antihiperglucemiante (si procede) que, en opinión del Investigador, no ha sido estable en las 12 semanas anteriores a la Selección o entre la Selección y la Aleatorización - Procedimiento coronario planificado o cirugía después de la aleatorización. - Complicaciones en las extremidades inferiores (como úlceras cutáneas, infecciones, osteomielitis y gangrena) identificadas durante la fase de Selección y que sigan precisando de tratamiento en la Aleatorización - Los pacientes que tienen previsto iniciar tratamiento con un inhibidor del cotransportador sodio-glucosa tipo 2 (SGLT2) (distinto del fármaco del estudio) durante el estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Time to first Major Adverse Cardiovascular Event (MACE) : Time to the first occurrence of any of the following clinical events: Cardiovascular death, Non-fatal myocardial infarction (MI), Non-fatal stroke 2. Time to cardiovascular death or hospitalization for heart failure : Time to the first occurrence of any of the following clinical events: Cardiovascular death; Hospitalization for heart failure |
1. Tiempo hasta la primera aparición de cualquiera de los siguientes eventos clínicos: Muerte por causas cardiovasculares, IM no mortal, Accidente cerebrovascular no mortal 2. Tiempo hasta la primera aparición de cualquiera de los siguientes eventos clínicos: Muerte por causas cardiovasculares, Hospitalización por insuficiencia cardiaca |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. and 2. Baseline to approximately 51 months |
1 y 2. Desde la basal hasta aproximadamente 51 meses |
|
E.5.2 | Secondary end point(s) |
1. Time to first composite renal event : Time to the first occurrence of any of the following clinical events in patients with baseline eGFR ≥30 mL/min/1.73 m2: Sustained ≥50% decrease of eGFR from baseline (for ≥30 days); chronic dialysis, renal transplant or sustained eGFR <15 ml/min/1.73 m2 (for ≥30 days) 2. Time to first composite renal event in subgroup of patients with macroalbuminuria : Time to the first occurrence of any of the following clinical events in patients with baseline eGFR ≥30 mL/min/1.73 m2 and baseline UACR ≥300 mg/g: Sustained ≥50% decrease of eGFR from baseline (for ≥30 days); chronic dialysis, renal transplant or sustained eGFR <15 ml/min/1.73 m2 (for ≥30 days 3. Total number of heart failure events : Total number (ie, including recurrent events) of the following clinical events: Cardiovascular death, Hospitalization for heart failure; Urgent heart failure visit 4. Cardiovascular (CV) death : Time to CV death 5. All cause mortality : Time to all-cause mortality |
1. Tiempo transcurrido hasta la primera aparición de cualquiera de los siguientes eventos clínicos en pacientes con eGFR basal ≥30 mL / min / 1.73 m2: Disminución sostenida ≥ 50% del eGFR desde la línea de base (durante ≥30 días) ; diálisis crónica, trasplante renal o eGFR sostenido <15 ml / min / 1,73 m2 (durante ≥ 30 días) 2. Tiempo hasta el primer evento renal compuesto en subgrupo de pacientes con macroalbuminuria: Tiempo transcurrido hasta la primera ocurrencia de cualquiera de los siguientes eventos clínicos en pacientes con eGFR basal ≥30 mL / min / 1.73 m2 y UACR basal ≥300 mg / g: ≥ 50% de disminución de eGFR desde la línea de base (durante ≥ 30 días); diálisis crónica, trasplante renal o eGFR sostenido <15 ml / min / 1,73 m2 (por ≥ 30 días 3. Número total de eventos de insuficiencia cardiaca: Número total (es decir, incluyendo eventos recurrentes) de los siguientes eventos clínicos: Muerte cardiovascular, Hospitalización por insuficiencia cardíaca; Visita urgente de insuficiencia cardiaca 4. Muerte cardiovascular (CV): Tiempo hasta la muerte CV 5. Mortalidad por todas las causas: Tiempo hasta la mortalidad por todas las causas |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. to 5. Baseline to approximately 51 months |
1 al 5. Desde la basal hasta aproximadamente 51 meses |
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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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 222 |
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 |
Bulgaria |
Canada |
Chile |
China |
Czech Republic |
Denmark |
Estonia |
France |
Georgia |
Germany |
Greece |
Guatemala |
Hungary |
India |
Israel |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Macedonia, the former Yugoslav Republic of |
Mexico |
Netherlands |
New Zealand |
Norway |
Peru |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
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
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Last Subject Last Visist (LSLV) |
Última visita del último paciente (LPLV) |
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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 | |
E.8.9.1 | In the Member State concerned months | 52 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 52 |