E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus |
Diabetes mellitus tipo 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes mellitus |
Diabetes mellitus tipo 2 |
|
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.1.3 | 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, efpeglenatide doses 1 and 2 is noninferior to placebo on 3-point major adverse cardiac event (MACE) in Type 2 diabetes mellitus (T2DM) patients at high cardiovascular (CV) risk. |
Demostrar que efpeglenatida en la dosis 1 (4 mg) y dosis 2 (6 mg) no es inferior al placebo en los acontecimientos cardiacos adversos graves (MACE) de 3 puntos en pacientes con diabetes mellitus tipo 2 (DMT2) y alto riesgo cardiovascular (CV.) |
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E.2.2 | Secondary objectives of the trial |
-To demonstrate that efpeglenatide doses 1 and 2 is superior to placebo in T2DM patients with high CV risk on the following parameters: -3-point MACE -Expanded CV outcome. -Composite outcome of new or worsening nephropathy. -To assess the safety and tolerability of efpeglenatide doses 1 and 2, both added to standard of care in T2DM patients at high CV risk. |
Demostrar que efpeglenatida en la dosis 1 (4 mg) y dosis 2 (6 mg) es superior al placebo en los acontecimientos cardiacos adversos graves (MACE) de 3 puntos en pacientes con diabetes mellitus tipo 2 (DMT2) y alto riesgo cardiovascular (CV) en los siguientes parámetros: - acontecimientos cardiacos adversos graves (MACE) de 3 puntos - resultado CV ampliado - el resultado compuesto de aparición o empeoramiento de nefropatía Evaluar la seguridad y tolerabilidad de efpeglenatida de la dosis 1 (4 mg) y dosis 2 (6 mg), ambas dosis añadidas al tratamiento estándar en pacientes con DMT2 y alto riesgo CV. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Type 2 Diabetes Mellitus with glycosylated hemoglobin (HbA1c) > 7%. -Age 18 years or older with established cardiovascular disease or age 50 years (male), 55 years (female) or older with eGFR ≥25 and <60 mL/min and at least one cardiovascular risk factor. -Male and female patients must agree to follow contraceptive guidance. -Signed written informed consent. |
- Diabetes mellitus Tipo 2 con hemoglobina glucosilada (HbA1c)> 7%. - Edad 18 años o más con enfermedad cardiovascular establecida o edad 50 años (varón), 55 años (mujer) o más, una TFGe de ≥25 y <60 ml/min y al menos uno de los 6 factores de riesgo cardiovascular. - Los pacientes hombres o mujeres deben aceptar seguir la guía de anticoncepción. - Consentimiento informado firmado por escrito. |
|
E.4 | Principal exclusion criteria |
-Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting. -History of chronic pancreatitis or acute idiopathic pancreatitis or diagnosis of any type of acute pancreatitis. -Personal or family history of medullary thyroid cancer (MTC) -Hypertension (with a systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg). -Hospitalization for hypertensive emergency within 3 months prior to randomization -Planned coronary procedure or surgery after randomization. -No documented ophthalmologic exam with fundoscopy within 6 months prior to screening -Retinopathy or maculopathy with treatment, either recent (3 months prior to randomization) or planned during the study -Treated with any glucagon-like peptide-1 (GLP-1) receptor agonist products (eg, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide) within 3 months prior to screening. -Use of any DPP4 inhibitor within 12 weeks prior to screening -Antihyperglycemic treatment has not been stable within 12 weeks prior to screening. |
- Historial clínicamente relevante de enfermedad gastrointestinal asociada con náuseas y vómitos prolongados. -Historia de pancreatitis crónica o pancreatitis idiopática aguda o diagnóstico de cualquier tipo de pancreatitis aguda. Historial personal o familiar de cáncer medular tiroideo (CMT). -Hipertensión (con una presión arterial sistólica superior a 180 mmHg y / o presión arterial diastólica superior a 100 mmHg). - Hospitalización por urgencia hipertensiva en los 3 meses anteriores a la aleatorización. -Procedimiento coronario planificado o cirugía después de la aleatorización. - Falta de examen oftalmológico con fundoscopia documentado en los 6 meses anteriores a la selección -Retinopatía o maculopatía con tratamiento, ya sea reciente (3 meses antes de la aleatorización) o planificada durante el estudio - Tratado con cualquier producto agonista del receptor del péptido 1 (GLP-1) similar al glucagón (p. Ej., Exenatida, liraglutida, lixisenatida, albiglutida, dulaglutida, semaglutida) dentro de los 3 meses previos a la selección. - Uso de cualquier inhibidor de la DPP-4 en las 12 semanas anteriores a la selección. - Tratamiento diabético que, en opinión del Investigador, no ha sido estable en las 12 semanas anteriores a la selección. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
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 |
El tiempo hasta la primera aparición del acontecimiento cardiaco adversos grave (MACE): tiempo hasta la primera aparición de uno de los siguientes eventos: muerte por causas CV, Infato de Miocardio no mortal, o accidente cerebrovascular no mortal) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to approximately 36 months |
Basal hasta aproximadamente 36 meses |
|
E.5.2 | Secondary end point(s) |
1) Time to first expanded cardiovascular outcome event: Time to the first occurrence of any of the following clinical events, positively adjudicated by the clinical endpoint committee (CEC): cardiovascular death, non-fatal MI, non-fatal stroke, coronary revascularization, hospitalization for unstable angina. 2) Time to first composite renal event: Time to the first occurrence of any of the following clinical events: new onset or progression to macro albuminuria (>300 mg/g) accompanied by a UACR value increase of ≥30% from baseline, sustained ≥40% decrease in eGFR from baseline (for ≥30 days), chronic dialysis (for ≥90 days), renal transplant, sustained eGFR <15 mL/min/1.73 m2 (for ≥30 days). 3) Adverse Events (AEs): Number of patients with AEs |
1) Tiempo hasta el primer evento de resultado cardiovascular ampliado: tiempo hasta la primera aparición de cualquiera de los siguientes eventos clínicos, adjudicados positivamente por el Comité de Acontecimientos Clínicos (CAC): muerte cardiovascular, infarto de miocardio no mortal, accidente cerebrovascular no mortal, revascularización coronaria, hospitalización por angina inestable. 2) Tiempo hasta el primer evento renal compuesto: tiempo hasta la primera aparición de cualquiera de los siguientes eventos clínicos: nueva aparición o progresión a macroalbuminuria (>300 mg/g) acompañada por un aumento del valor del CACo ≥30 % desde el inicio del estudio, Disminución sostenida ≥40 % en la TFGe desde el inicio del estudio (durante ≥30 días), Diálisis crónica (durante ≥90 días), Trasplante renal, TFGe mantenida <15 ml/min/1,73 m2 (durante ≥30 días). 3) Acontecimiento adversos (AEs): Número de pacientes con Acontecimientos adversos (AEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) to 3) Baseline to approximately 36 months |
Del 1) al 3) Basal hasta aproximadamente 36 meses |
|
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) | 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 | 3 |
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 | 123 |
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 |
Bulgaria |
Canada |
Chile |
Denmark |
Estonia |
Finland |
Germany |
Hungary |
India |
Italy |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Norway |
Peru |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Sweden |
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
|
LVLS |
Última visita del último paciente |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |