E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus |
Diabetes Mellitus Tipo 2 |
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E.1.1.1 | Medical condition in easily understood language |
Cardiovascular disease in patients with type 2 diabetes |
Enfermedad Cardiovascular en pacientes con Diabetes Mellitus tipo 2 |
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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 | 16.1 |
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 |
The primary objective of EXSCEL will be to evaluate the effect of exenatide once weekly (EQW), used in addition to the current usual care for glycemic control, on major macrovascular events when administered to patients with type 2 diabetes. |
El objetivo principal de EXSCEL es evaluar los efectos de EUS una vez a la semana, en su adición al tratamiento habitual actual para el control de la glucemia, sobre los acontecimientos macrovasculares mayores en su administración a pacientes con diabetes de tipo 2. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of EXSCEL are to evaluate the effect of EQW treatment used in addition to the current usual care for glycemic control on: (1) All cause mortality (2) Each of the components of the primary composite CV endpoint (3) Hospitalization for acute coronary syndrome (ACS) (4) Hospitalization for congestive heart failure (CHF) |
Los objetivos secundarios de EXSCEL son evaluar los efectos del tratamiento con EUS utilizado en adición al tratamiento habitual actual para el control glucémico sobre: 1) Muerte por todas las causas 2) Cada uno de los componentes del criterio de valoración CV compuesto principal 3) Hospitalización por síndrome coronario agudo (SCA) 4) Hospitalización por insuficiencia cardiaca congestiva (ICC) |
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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 |
Patients enrolled in the trial will have the option to consent separately to provide a whole blood sample for future pharmacogenomic analyses. The objective of collecting blood samples from which genetic analyses can be performed is to investigate the relationships between genetic make-up and clinical events. These samples will be drawn at baseline, or at any point in the trial at which consent is obtained from the patient. Patients enrolled in the trial will be asked to consent separately to provide two blood and one urine samples for future biomarker analyses. These specimens (preferably fasting) will be obtained at baseline (prior to drug exposure), annually and trial/early termination. |
A los pacientes participantes en el ensayo se les pedirá su consentimiento por separado para la obtención de una muestra de sangre completa para futuros análisis farmacogenómicos. El objetivo de la recogida de muestras de sangre para la práctica de análisis genéticos es investigar las relaciones entre la estructura genética y los acontecimientos clínicos. Dichas muestras se obtendrán en el momento basal o en cualquier otro momento del ensayo en el que el paciente otorgue su consentimiento |
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E.3 | Principal inclusion criteria |
- Patient has type 2 diabetes mellitus - Patient will able to see a usual care provider at least twice a year - Patient has an HbA1c of >= 6.5% and <= 10.0% and is currently using one of the following treatment regimens: ?Treatment with up to three (i.e., 0-3) oral AHAs (concomitant use of DPP-4 inhibitors is permitted). ?Insulin therapy, either alone or in combination with up to two (ie., 0-2) oral AHAs (use of basal and prandial insulins is permitted in any combination of individual or premixed insulins) All patients should be on a stable diabetes management regimen, as assessed by the investigator, at the time of enrollment. - Patients with any level of CV risk. - Female patients must not be breast feeding and agree to use an effective method of contraception or must not otherwise be at risk of becoming pregnant. - Patient agrees to provide permission to obtain all medical records necessary for complete data ascertainment during the follow-up period, and agrees to communication between the trial site and the usual care provider in order to facilitate routine care. - Patient is 18 years or older at enrollment. |
a) Diabetes mellitus de tipo 2 b) Paciente capaz de acudir a su médico habitual como mínimo dos veces al año c) Paciente con HbA1c >= 6,5 % y <= 10,0% y que actualmente está con uno de los siguientes regímenes terapéuticos: ? Tratamiento con un máximo de tres (es decir, 0-3) AAH orales (se permite el uso concomitante de inhibidores de DPP-4) ? Insulina, bien sola o en combinación con un máximo de dos (es decir, 0-2) AAH orales (se permite el uso de insulinas basales y prandiales en cualquier combinación de insulinas individuales o premezclas) - Pacientes con cualquier nivel de riesgo CV. - Las mujeres no podrán estar amamantando y deberán mostrar su conformidad en utilizar un método anticonceptivo eficaz o, en caso contrario, no tener riesgo de embarazo. - Paciente que da su autorización para la obtención de todos los documentos médicos necesarios para poder disponer de los datos completos durante el período de seguimiento y que está de acuerdo en la comunicación entre el centro del estudio y su médico habitual para facilitar su atención normal. -Paciente de 18 años o más en el momento de su reclutamiento |
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E.4 | Principal exclusion criteria |
- Patient has a diagnosis of type 1 diabetes mellitus, or a history of ketoacidosis. - Patient has a history (>= 2 episodes) of severe hypoglycemia within 12 months of enrollment. - Patient has ever been treated with an approved or investigational GLP-1 receptor agonist e.g. exenatide BID, exenatide once weekly, liraglutide, lixisenatide, albiglutide, taspoglutide, or dulaglutide. - Patient is enrolled in another experimental protocol which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial. - Patient has a planned or anticipated revascularization procedure. - Pregnancy or planned pregnancy during the trial period. - Patient has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose an unacceptable risk to the patient, confound the results of the trial e.g. if patient cannot comply with requirements of the trial, or likely to interfere with the patient?s participation for the full duration of the trial. - Patient has end-stage renal disease or an estimated glomerular filtration rate of <30 mL/min/1.73 m2. - Patient has a history of gastroparesis. - Personal or family history of medullary thyroid cancer or MEN2 (Multiple Endocrine Neoplasia Type 2) or calcitonin level > 40ng/L at baseline. - Patient has previously been enrolled in EXSCEL. - Patient has a history of pancreatitis. - Is an employee of Amylin Pharmaceuticals LLC, Bristol-Myers Squibb Company or AstraZeneca. |
- Paciente con diagnóstico de diabetes mellitus de tipo 1 o antecedentes de cetoacidosis. - Paciente con antecedentes (>= 2 episodios) de hipoglucemia severa en el plazo de los 12 meses anteriores a su reclutamiento. -Paciente que ha recibido tratamiento en algún momento con un agonista del receptor de GLP-1, ya sea aprobado o en investigación, como, por ejemplo, BYETTA (exenatida), BYDUREON (EUS), VICTOZA (liraglutida), LYXUMIA (lixisenatida), albiglutida, taspoglutida o dulaglutida. -Paciente que está participando en otro protocolo experimental que supone el uso de un medicamento o producto sanitario en investigación o de una intervención que pudiera interferir con el desarrollo de este ensayo. - Paciente con procedimiento de revascularización programado o previsible - Embarazo o búsqueda de embarazo durante el periodo del ensayo - Paciente con antecedente o evidencia actual de cualquier proceso, tratamiento, anomalía de laboratorio u otra circunstancia que, en opinión del investigador o coordinador, pueda conllevar un riesgo inaceptable para el paciente, confundir los resultados del ensayo (por ejemplo, si el paciente no pudiera cumplir con los requisitos del ensayo) o con probabilidad de interferir con la participación del paciente durante toda la duración del ensayo - Paciente con nefropatía terminal o con una tasa de filtración glomerular estimada (TFGe) obtenida a partir de su creatinina sérica (utilizando la fórmula sencilla del MDRD-4) <30 mL/min/1,73m2 - Paciente con historia de gastroparesia - Antecedentes personales o familiares de cáncer medular de tiroides o de MEN2 (neoplasia endocrina múltiple de tipo 2) o nivel de calcitonina> 40 ng/L en el momento basal. - Paciente que ya ha sido anteriormente aleatorizado en EXSCEL - Paciente con antecedente de pancreatitis - Paciente que es empleado de Amylin Pharmaceuticals, LLC, Bristol -Myers Squibb Company, o de AstraZeneca |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: Time to first confirmed CV event in the primary composite CV endpoint. Defined as the time from randomization to first confirmed CV-related death, nonfatal MI or nonfatal stroke. |
Criterio de valoración principal de la eficacia:Tiempo hasta el primer acontecimiento CV confirmado del criterio de valoración CV compuesto principal.Definido como el tiempo desde la aleatorización al primer acontecimiento confirmado de muerte de causa CV, IM no fatal o accidente cerebrovascular no fatal. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1360 patients with positively adjudicated primary endpoint events have been accrued |
1360 pacientes con el criterio de valoracíón principal de eficacia positivamente adjudicado acumulados |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints: - Time to all-cause mortality. Defined as time from randomization to death due to any cause. - Time to first confirmed CV event for each component of the primary composite endpoint. - Time to hospitalization for acute coronary syndrome. - Time to hospitalization for heart failure. |
Criterios secundarios de valoración de la eficacia ? Tiempo hasta el fallecimiento por cualquier causa Definido como el tiempo desde la aleatorización a la muerte por cualquier causa. ? Tiempo hasta el primer acontecimiento CV confirmado de cada componente del criterio de valoración CV compuesto principal. ? Tiempo hasta la hospitalización por síndrome coronario agudo. ? Tiempo hasta la hospitalización por insuficiencia cardiaca |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1360 patients with positively adjudicated primary endpoint events have been accrued |
1360 pacientes con el criterio de valoracíón principal de eficacia positivamente adjudicado acumulados. |
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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 | 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 | 19 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 261 |
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 |
Belgium |
Bulgaria |
Canada |
China |
Netherlands |
New Zealand |
Argentina |
Australia |
Brazil |
Chile |
Colombia |
Hong Kong |
India |
Korea, Republic of |
Malaysia |
Spain |
Thailand |
Israel |
Mexico |
Peru |
Philippines |
Russian Federation |
South Africa |
Taiwan |
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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LVLS |
Ultima visita del último paciente. |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |