E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Diabetes mellitus tipo 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Diabetes 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 | 19.0 |
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 |
|
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 |
The primary objective is to confirm that treatment with oral semaglutide does not result in an unacceptable increase in cardiovascular risk compared to placebo (rule out 80% excess risk) in subjects with type 2 diabetes at high risk of cardiovascular events |
El objetivo principal consiste en confirmar que el tratamiento con semaglutida oral no conlleva un aumento inaceptable del riesgo cardiovascular en comparación con placebo (descartar un exceso de riesgo del 80%) en sujetos con diabetes tipo 2 y un riesgo elevado de sufrir acontecimientos cardiovasculares. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare the efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes at high risk of cardiovascular events |
Los objetivos secundarios consisten en comparar la eficacia y la seguridad de semaglutida oral con respecto a placebo en sujetos con diabetes tipo 2 y un riesgo elevado de sufrir acontecimientos cardiovasculares. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female diagnosed with type 2 diabetes 2. Age ? 50 years at screening and presence of cardiovascular disease, or age ? 60 years at screening and presence of at least one cardiovascular risk factor |
1. Sujeto de uno u otro sexo diagnosticado de diabetes tipo 2. 2. Edad ? 50 años en el momento de selección y presencia de alguna enfermedad cardiovascular o edad ? 60 años en el momento de selección y presencia de al menos un factor de riesgo cardiovascular. |
|
E.4 | Principal exclusion criteria |
1. Current or previous (within 90 days prior to screening) treatment with any GLP-1 receptor agonist, DPP-4 inhibitor or pramlintide 2. Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC) 3. History of pancreatitis (acute or chronic) 4. History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery) 5. Subjects presently classified as being in New York Heart Association (NYHA) Class IV heart failure 6. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening 7. Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 60 days prior to screening 8. Chronic or intermittent hemodialysis or peritoneal dialysis or severe renal impairment (corresponding to eGFR <30 mL/min/1.73 m^2) 9. History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ) |
1. Tratamiento previo (en los 90 días previos a la selección) o presente con cualquier agonista del receptor de GLP-1, inhibidor de DPP-4 o pramlintida. 2. Antecedentes personales o familiares de síndrome de neoplasias endocrinas múltiples tipo 2 (NEM2) o carcinoma medular de tiroides (CMT). 3. Antecedentes de pancreatitis (aguda o crónica). 4. Antecedentes de intervenciones de cirugía mayor que afecten al estómago y que podrían afectar a la absorción del producto del ensayo (por ejemplo, gastrectomía subtotal y total, gastrectomía en manguito o intervención de derivación gástrica). 5. Sujetos con insuficiencia cardíaca en clase funcional IV según la New York Heart Association (NYHA). 6. Revascularización arterial coronaria, carotídea o periférica ya programada el día de la selección. 7. Cualquiera de las circunstancias siguientes: infarto de miocardio, ictus u hospitalización por angina de pecho inestable o accidente isquémico transitorio, en los 60 días previos a la selección. 8. Hemodiálisis o diálisis peritoneal crónica o intermitente o insuficiencia renal grave (correspondiente a una FGe < 30 ml/min/1,73 m2). 9. Antecedentes o presencia de una neoplasia maligna en los últimos 5 años (excepto carcinoma basocelular o espinocelular de piel y carcinomas in situ). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time from randomisation to first occurrence of a major adverse cardiovascular event (MACE) composite endpoint consisting of: cardiovascular death, non-fatal myocardial infarction or non-fatal stroke |
Tiempo transcurrido entre la aleatorización y el primer episodio de un criterio de valoración combinado de acontecimientos cardiovasculares adversos importantes (MACE), definido como muerte de origen cardiovascular, infarto de miocardio no mortal o ictus no mortal. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months |
La duración máxima del tratamiento dependerá de las tasas de acontecimientos y se calcula que no será superior a 19 meses. |
|
E.5.2 | Secondary end point(s) |
1. Time from randomisation to first occurrence of an expanded composite cardiovascular endpoint consisting of: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalisation or hospitalisation for heart failure 2. Time from randomisation to first occurrence of each of the individual components in the expanded composite cardiovascular endpoint 3. Time from randomisation to first occurrence of a composite endpoint consisting of: all-cause death, non-fatal myocardial infarction or non-fatal stroke |
1. Tiempo transcurrido entre la aleatorización y el primer episodio de un criterio de valoración cardiovascular combinado ampliado, definido como muerte de origen cardiovascular, infarto de miocardio no mortal, ictus no mortal, angina de pecho inestable con necesidad de hospitalización u hospitalización por insuficiencia cardíaca. 2. Tiempo transcurrido entre la aleatorización y el primer episodio de cada uno de los componentes individuales del criterio de valoración cardiovascular combinado ampliado. 3. Tiempo transcurrido entre la aleatorización y el primer episodio de un criterio de valoración combinado, definido como muerte por cualquier causa, infarto de miocardio no mortal o ictus no mortal. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
All endpoints: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months |
Todos los criterios de valoración principal y secundarios fundamentales, la duración máxima del tratamiento dependerá de las tasas de acontecimientos y se calcula que no será superior a 19 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 | 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Algeria |
Argentina |
Brazil |
Canada |
European Union |
India |
Israel |
Malaysia |
Mexico |
South Africa |
Taiwan |
Thailand |
Turkey |
United States |
|
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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |