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 | 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 |
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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 once-daily dosing of 14 mg oral semaglutide versus 25 mg empagliflozin, both in combination with metformin, on glycaemic control in subjects with type 2 diabetes mellitus |
Comparar el efecto de la administración una vez al día de 14 mg de semaglutida oral y 25 mg de empagliflozina, ambas en combinación con metformina, sobre el control de la glucemia en pacientes con diabetes mellitus tipo 2. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the effect of once-daily dosing of 14 mg oral semaglutide versus 25 mg empagliflozin, both in combination with metformin, on body weight in subjects with type 2 diabetes mellitus. 2. To compare the safety and tolerability of once-daily dosing of 14 mg oral semaglutide versus 25 mg empagliflozin, both in combination with metformin, in subjects with type 2 diabetes mellitus |
1.Comparar el efecto de la administración una vez al día de 14 mg de semaglutida oral y 25 mg de empagliflozina, ambas en combinación con metformina, sobre el peso corporal en pacientes con diabetes mellitus tipo 2. 2.Comparar la seguridad y tolerabilidad de la administración una vez al día de 14 mg de semaglutida oral y 25 mg de empagliflozina, ambas en combinación con metformina, en pacientes con diabetes mellitus tipo 2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. 2. Male or female, age above or equal to 18 years at the time of signing informed consent. 3. Diagnosed with type 2 diabetes mellitus ? 90 days prior to day of screening. 4. HbA1c of 7.0-10.5 % (53-91 mmol/mol) (both inclusive). 5. Stable daily dose of metformin (? 1500 mg or maximum tolerated dose as documented in the subject medical record) ? 90 days prior to the day of screening. |
1.Obtención del consentimiento informado antes de realizar ninguna actividad relacionada con el ensayo. Se consideran actividades relacionadas con el ensayo todos los procedimientos realizados como parte del mismo, incluidas las actividades realizadas para determinar si se cumplen los requisitos de participación. 2.Varones o mujeres de 18 o más años de edad en el momento de firmar el consentimiento informado. 3.Diagnóstico de diabetes mellitus tipo 2 ? 90 días antes del día de la selección. 4.HbA1c de 7,0 % 10,5 % (53 91 mmol/mol) (ambos valores inclusive). 5.Dosis diaria estable de metformina (? 1500 mg o dosis máxima tolerada, tal como se documente en la historia clínica del paciente) ? 90 días antes del día de la selección. |
|
E.4 | Principal exclusion criteria |
1. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). For certain specific countries: Additional specific requirements apply. 2. Any disorder, which in the investigator?s opinion might jeopardise subject?s safety or compliance with the protocol. 3. Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma. 4. History of pancreatitis (acute or chronic). 5. 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). 6. Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening. 7. Subjects presently classified as being in New York Heart Association Class IV. 8. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening. 9. Subjects with ALT > 2.5 x upper normal limit. 10. Renal impairment defined as Estimated Glomerular Filtration Rate < 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). 11. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of ? 14 days. 12. Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation. 13. History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ). 14. History of diabetic ketoacidosis. |
1.Mujeres embarazadas, en período de lactancia, que pretendan quedarse embarazadas o que estén en edad fértil y no utilicen métodos anticonceptivos adecuados (según exija la normativa o práctica local). En determinados países específicos: Se aplican otros requisitos específicos. 2.Cualquier trastorno que, en opinión del investigador, pueda poner en peligro la seguridad del paciente o el cumplimiento del protocolo. 3.Antecedentes personales o familiares de Neoplasia Endocrina Múltiple de Tipo 2 o Carcinoma Medular de Tiroides. 4.Antecedentes de pancreatitis (aguda o crónica). 5.Antecedentes de procedimientos de cirugía mayor en el estómago que puedan afectar a la absorción del producto del ensayo (p. ej., gastrectomía subtotal y total, gastrectomía vertical, cirugía de derivación gástrica). 6.Cualquiera de lo siguiente: infarto de miocardio, ictus u hospitalización por angina inestable o accidente isquémico transitorio en los 180 días previos al día de la selección. 7.Pacientes con una clase IV de la New York Heart Association. 8.Revascularización arterial coronaria, carotídea o periférica programada que se conozca el día de la selección. 9.Pacientes con ALT > 2,5 x límite superior de la normalidad. 10.Insuficiencia renal, definida como una Filtración Glomerular Estimada < 60 ml/min/1,73 m2 según la fórmula de la Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). 11.Tratamiento con fármacos indicados para la diabetes o la obesidad distintos de los especificados en los criterios de inclusión durante un periodo de 90 días antes del día de la selección. Constituye una excepción el tratamiento breve con insulina para la enfermedad aguda durante un total de ? 14 días. 12.Retinopatía proliferativa o maculopatía que requieran tratamiento urgente. Verificada mediante fotografía del fondo de ojo u oftalmoscopia con dilatación en los 90 días previos a la aleatorización. 13.Antecedentes o presencia de neoplasias malignas en los últimos 5 años (excepto carcinoma basocelular y carcinoma de células escamosas de la piel y carcinoma in situ). 14.Antecedente de cetoacidosis diabética. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in glycosylated haemoglobin (HbA1c) |
Variación de la hemoglobina glucosilada (HbA1c) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 26 |
Entre el momento basal y la semana 26 |
|
E.5.2 | Secondary end point(s) |
1. Change in HbA1c 2. Change in body weight (kg) 3. Change in fasting plasma glucose 4. Achieved HbA1c < 7.0 % (53 mmol/mol) American Diabetes Association target (yes/no) 5. Number of treatment-emergent adverse events 6. Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes |
1.Variación de la HbA1c 2.Variación en el Peso corporal (kg) 3.Variación en la Glucosa plasmática en ayunas 4.HbA1c< 7,0 % (53 mmol/mol) (objetivo de la American Diabetes Association)(si/no) 5.Número de acontecimientos adversos de aparición 6.Número de episodios de hipoglucemia grave o sintomáticao confirmada mediante determinación de la glucemia de aparición |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From baseline to week 52 2. + 3. From baseline to week 26 and week 52 4. After week 26 and week 52 5. + 6. During exposure to trial product, assessed up to approximately 57 weeks |
2. + 3.Entre visita basal y semanas 26 y 52 4. Después de las semanas 26 y 52 5. + 6. Durante la exposición al producto de ensayo, evaluado hasta aproximadamente 57 semanas |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
|
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Brazil |
European Union |
Russian Federation |
Serbia |
Thailand |
United States |
|
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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 3 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 3 |