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 | 14.1 |
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 confirm superiority of switch from sitagliptin 100 mg/day to liraglutide 1.8 mg/day, both + metformin vs. continued sitagliptin 100 mg/day + metformin on glycaemic control after 26 weeks of treatment in subjects with type 2 diabetes. |
Confirmar la superioridad del cambio de sitagliptina 100 mg/día a liraglutida 1,8 mg/día, ambas + metformina sobre el tratamiento continuado con sitagliptina 100 mg/día + metformina en relación con el control de la glucemia después de 26 semanas de tratamiento en pacientes con diabetes de tipo 2 |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of switch from sitagliptin 100 mg/day to liraglutide 1.8 mg/day, both + metformin vs. continued sitagliptin 100 mg/day + metformin after 26 weeks of treatment in subjects with type 2 diabetes. - selected parameters of anthropometry - selected cardiovascular risk factors - safety and tolerability |
Comparar el efecto del cambio de sitagliptina 100 mg/día a liraglutida 1,8 mg/día, ambas + metformina con el del tratamiento continuado con sitagliptina 100 mg/día + metformina después de 26 semanas de tratamiento en pacientes con diabetes de tipo 2 sobre: ?Determinados parámetros antropométricos. ?Determinados factores de riesgo cardiovascular. ?Seguridad y tolerabilidad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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 - Male or female, age ? 18 years - Subjects diagnosed with type 2 diabetes and treated with metformin ? 1500 mg/day (or maximum tolerated dose ? 1000 mg/day) and sitagliptin 100 mg/day, both at a stable dose for at least 90 days prior to screening. Stable is defined as unchanged medication and dose - HbA1c 7.5% ? 9.5% (58 mmol/mol ? 80 mmol/mol) (both inclusive) - Body mass index ? 20 kg/m^2 |
?Obtención del consentimiento informado antes de realizar actividades relacionadas con el ensayo. Se consideran actividades relacionadas con el ensayo todos los procedimientos que se lleven a cabo como parte del ensayo, incluidas las actividades para determinar la idoneidad para el ensayo. ?Varón o mujer con una edad mínima de 18 años. ?Paciente diagnosticado de diabetes de tipo 2 y tratado con metformina ? 1500 mg/día (o la dosis máxima tolerada ? 1000 mg/día) y sitagliptina 100 mg/día, ambas en dosis estables durante al menos 90 días antes de la selección. Se define ?estable? como un fármaco y una dosis inalterados. ?HbA1c del 7,5%?9,5% (58?80 mmol/mol) (ambos inclusive). ?Índice de masa corporal ? 20 kg/m2. |
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E.4 | Principal exclusion criteria |
- Any chronic disorder or severe disease which at the discretion of the investigator might jeopardise subject?s safety or compliance with the protocol - Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. An exception is short-term treatment (? 7 days in total) with insulin in connection with intercurrent illness - Female who is pregnant, breast-feeding, intends to become pregnant or of child-bearing potential not using adequate contraceptive methods (adequate contraceptive measures as required by local regulations or practice) - History of chronic pancreatitis or idiopathic acute pancreatitis - Screening calcitonin value ? 50 ng/L - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 - Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer) - Impaired liver function, defined as alanine aminotransferase ? 2.5 times upper normal limit - Impaired renal function defined as estimated glomerular filtration rate < 60 mL/min/1.73 m^2 per modification of diet in renal disease formula - Any episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack or other significant cardiovascular event as judged by the investigator within 90 days prior to screening - Heart failure, New York Heart Association class IV - Uncontrolled treated or untreated hypertension (systolic blood pressure ?180 mmHg and/or diastolic blood pressure ?100 mmHg) |
?Cualquier trastorno crónico o enfermedad importante que, en opinión del investigador, pueda poner en peligro la seguridad del paciente o el cumplimiento del protocolo. ?Tratamiento con fármacos hipoglucemiantes distintos de los especificados en los criterios de inclusión en un período de 90 días antes de la selección. Una excepción es el tratamiento a corto plazo (? 7 días en total) con insulina por una enfermedad intercurrente. ?Mujeres embarazadas, en período de lactancia, que pretendan quedarse embarazadas o que estén en edad fértil y no utilicen métodos anticonceptivos adecuados (según exijan la normativa o práctica local). ?Antecedentes de pancreatitis crónica o pancreatitis aguda idiopática. ?Valor de calcitonina ? 50 ng/l en la visita de selección. ?Antecedentes personales o familiares de carcinoma medular de tiroides o de síndrome de neoplasias endocrinas múltiples de tipo 2. ?Diagnóstico de neoplasia maligna en los 5 años previos (excepto cáncer basocelular o espinocelular de piel). ?Disfunción hepática, definida como un valor de alanina aminotransferasa ? 2,5 veces el límite superior de la normalidad. ?Disfunción renal, definida como una filtración glomerular estimada < 60 ml/min/1,73 m2 según la fórmula MDRD (Modificación de la dieta en la nefropatía). ?Cualquier episodio de angina de pecho inestable, episodio coronario agudo, ictus cerebral/accidente isquémico transitorio u otro episodio cardiovascular importante, a juicio del investigador, en los 90 días previos a la selección. ?Insuficiencia cardíaca en clase IV de la New York Heart Association. ?Hipertensión arterial tratada e incontrolada o no tratada (presión arterial sistólica ? 180 mm Hg o presión arterial diastólica ? 100 mm Hg). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c This endpoint will be evaluated as the mean treatment difference. |
?Variación de la HbA1c Este criterio de valoración se evaluará como la diferencia media entre los tratamientos. |
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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 |
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E.5.2 | Secondary end point(s) |
Confirmatory secondary endpoint 1. Change in body weight This endpoint will be evaluated as the mean treatment difference.
Key supportive secondary endpoints Change in: 2. Fasting plasma glucose 3. Fasting blood lipids 4. Systolic blood pressure and diastolic blood pressure These endpoints will be evaluated as the mean treatment differences.
Subjects who achieve (y/n): 5. HbA1c < 7.0% (53 mmol/mol) (American Diabetes Association target) This endpoint will be evaluated as the odds ratio between treatments.
Safety endpoints 6. Number of treatment emergent adverse events |
Criterio de valoración secundario confirmatorio 1.Variación del peso corporal. Este criterio de valoración se evaluará como la diferencia media entre los tratamientos Criterios de valoración secundarios de apoyo fundamentales Variación de: 2.Glucemia en ayunas. 3.Lipidemia en ayunas. 4.Presión arterial sistólica y diastólica. Estos criterios de valoración se evaluarán como la diferencia media entre los tratamientos Pacientes que logren (sí/no): 5.HbA1c < 7,0% (53 mmol/mol) (objetivo de la American Diabetes Association). Este criterio de valoración se evaluará como la razón de posibilidades entre los tratamientos. Criterios de valoración de la seguridad 6.Número de acontecimientos adversos aparecidos con el tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Confirmatory secondary endpoint 1. - 4. From baseline to Week 26 5. After 26 weeks of treatment 6. During 26 weeks of treatment |
Criterios de valoración secundarios confirmatorios. 1.-4.Desde el momento basal y la semana 26. 5. Después de 26 semanas de tratamiento. 6. Durante 26 semanas de tratamiento |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 |
European Union |
Canada |
India |
Israel |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 6 |