E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Diabetes Mellitus, tipo 2 |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Diabetes 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 | 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 compare the effect of semaglutide once-weekly on glycaemic control versus insulin aspart three times daily, both as add on to metformin and optimised insulin glargine (U100) in subjects with type 2 diabetes. |
Comparar el efecto sobre el control de la glucemia de semaglutida una vez a la semana frente a insulina aspart tres veces al día, ambas añadidas a metformina e insulina glargina optimizada (U100), en sujetos con diabetes tipo 2. |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate that semaglutide once-weekly lowers the risk of severe hypoglycaemic episodes compared to insulin aspart three times daily, both as add on to metformin and optimised insulin glargine (U100) in subjects with type 2 diabetes.
2. To compare the effect of semaglutide once-weekly versus insulin aspart three times daily, both as add on to metformin and optimised insulin glargine (U100) in subjects with type 2 diabetes with regards to: -body weight -lipids -blood pressure -health-related quality of life -safety |
1. Demostrar que semaglutida una vez a la semana reduce el riesgo de episodios de hipoglucemia grave en comparación con insulina aspart tres veces al día, ambas añadidas a metformina e insulina glargina optimizada (U100) en sujetos con diabetes tipo 2.
2. Comparar el efecto de semaglutida una vez a la semana frente a insulina aspart tres veces al día, ambas añadidas a metformina e insulina glargina optimizada (U100), en sujetos con diabetes tipo 2, en lo que se refiere a: - peso corporal - lípidos - presión arterial - calidad de vida relacionada con la salud - seguridad |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age greater than or equal to 18 years at the time of signing informed consent - Diagnosed with type 2 diabetes greater than or equal to 180 days prior to the day of screening - Treated with basal insulin once daily or twice daily for greater than or equal to 90 days prior to the day of screening - Stable daily dose for 90 days prior to the day of screening of the following anti-diabetic drugs or combination regimens: Any metformin formulations (greater than or equal to 1500 mg to less than or equal to 3000 mg or maximum tolerated or effective dose documented in subject's medical record), alone or in combination (including fixed-dose drug combination) with up to one additional of the following oral antidiabetic drugs: sulfonylureas, meglitinides, dipeptidyl peptidase-4 inhibitors or alpha-glucosidase inhibitors - Haemoglobin A1c (HbA1c) of greater than 7.5% to less than or equal to 10.0% (greater than 58 mmol/mol to less than or equal to 86 mmol/mol) |
- Pacientes de ambos sexos, de 18 años o más en el momento de la firma del consentimiento informado. - Diagnóstico de diabetes tipo 2 mayor o igual a 180 días antes del día de la selección. - Tratamiento con insulina basal una o dos veces al día durante mayor o igual a 90 días antes del día de la selección. - Dosis diaria estable de los siguientes antidiabéticos o regímenes combinados durante 90 días antes del día de la selección: cualquier formulación de metformina (mayor o igual a 1500 mg y menor o igual a 3000 mg o dosis máxima tolerada o eficaz documentada en la historia clínica del sujeto), sola o en combinación (incluida la combinación de dosis fijas) con hasta uno más de los siguientes antidiabéticos orales: sulfonilureas, meglitinidas, inhibidores de la dipeptidil peptidasa 4 o inhibidores de la alfa glucosidasa. - Hemoglobina A1c (HbA1c) mayor a 7,5% y menor o igual a 10,0% (mayor a 58 y menor o igual a 86 mmol/mol). |
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E.4 | Principal exclusion criteria |
- History or presence of pancreatitis (acute or chronic) - Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening - Subjects presently classified as being in New York Heart Association Class IV - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term bolus insulin treatment for a maximum of 14 days prior to the day of screening is allowed - Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to run-in |
- Antecedentes o presencia de pancreatitis (aguda o crónica). - Cualquiera de los siguientes: infarto de miocardio, ictus, hospitalización por angina inestable o accidente isquémico transitorio en los 180 días previos al día de la selección. - Sujetos con clase funcional IV según la New York Heart Association. - Revascularización arterial coronaria, carotidea o periférica ya programada que se conozca el día de la selección. - Tratamiento con fármacos indicados para la diabetes o la obesidad distintos de los especificados en los criterios de inclusión en el periodo de 90 días antes del día de la selección. Sin embargo, se permite el tratamiento con insulina en bolo a corto plazo durante un máximo de 14 días antes del día de la selección. - Retinopatía diabética o maculopatía no controlada y potencialmente inestable. Verificada mediante oftalmoscopia con midriasis farmacológica realizada por un oftalmólogo o un profesional sanitario de la misma cualificación (p. ej., optometrista) en los 90 días previos a la preinclusión (run-in). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c (%-point) |
Variación de la HbA1c (puntos %). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 52 |
Del momento basal a la semana 52 |
|
E.5.2 | Secondary end point(s) |
1. Time to first event adjudication committee confirmed severe hypoglycaemic episode (American Diabetes Association) 2. Time to first event adjudication committee confirmed severe hypoglycaemic episode (American Diabetes Association) requiring hospitalisation, documented medical help, or is life threatening 3. Change in body weight (kg) |
1. Tiempo transcurrido hasta el primer episodio, confirmado por el comité de adjudicación de eventos, de hipoglucemia grave (American Diabetes Association).
2. Tiempo transcurrido hasta el primer episodio, confirmado por el comité de adjudicación de eventos, de hipoglucemia grave (American Diabetes Association) con necesidad de hospitalización o de asistencia médica documentada o potencialmente mortal.
3. Variación del peso corporal (kg). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-2. From randomisation up to week 52 3. From baseline to week 52 |
1-2. Desde la aleatorización a la semana 52. 3. Desde el momento basal a la semana 52. |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 168 |
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 |
Bosnia and Herzegovina |
European Union |
India |
Macedonia, the former Yugoslav Republic of |
Serbia |
South Africa |
Turkey |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 12 |