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 | 18.0 |
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 confirm the efficacy of insulin degludec/liraglutide (IDegLira) in terms of glycaemic control in subjects with type 2 diabetes mellitus on previous treatment with insulin glargine (IGlar) and metformin. This is done by comparing the difference in change in HbA1c from baseline after 26 weeks of treatment to a non-inferiority limit of 0.30% for once daily IDegLira versus basal-bolus therapy with once daily IGlar plus prandial insulin aspart (IAsp), both arms in combination with metformin. |
Confirmar la eficacia de insulina degludec/liraglutida (IDegLira) en términos de control de la glucemia en sujetos con diabetes mellitus tipo 2 en tratamiento previo con insulina glargina (IGlar) y metformina. Para ello, se comparará la diferencia en la variación de la HbA1c desde el momento basal hasta después de 26 semanas de tratamiento, con un límite de no inferioridad del 0,30 %, entre IDegLira una vez al día y el tratamiento bolo-basal con IGlar una vez al día más insulina aspart prandial (IAsp), ambos grupos en combinación con metformina. |
|
E.2.2 | Secondary objectives of the trial |
1. To confirm superiority of IDegLira versus basal-bolus therapy in terms of: - number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during 26 weeks of treatment - change from baseline in body weight after 26 weeks of treatment 2. To compare general efficacy and safety of IDegLira versus basal-bolus therapy after 26 weeks of treatment. |
1. Confirmar la superioridad de IDegLira frente al tratamiento bolo-basal en cuanto a: - número de episodios emergentes graves sin tratamiento o episodios hipoglucémicos sintomáticos confirmados mediante determinación de glucemia en sangre en las últimas 26 semanas de tratamiento - variación del peso corporal con respecto al valor basal después de 26 semanas de tratamiento 2. Comparar la eficacia y la seguridad generales de IDegLira frente al tratamiento bolo-basal después de 26 semanas de tratamiento |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age ?18 years at the time of signing informed consent - Type 2 diabetes subjects (diagnosed clinically) ? 6 months prior to screening - HbA1c 7.0-10.0% [53mmol/mol-86mmol/mol] (both inclusive) by central laboratory analysis - Current treatment with IGlar for at least 90 calendar days prior to screening - Stable daily dose of IGlar between 20 units and 50 units (both inclusive) for at least 56 calendar days prior to screening. Individual fluctuations of ± 10% within the 56 calendar days prior to screening are acceptable, however on the day of screening total daily dose should be within the range of 20 units-50 units both inclusive - Stable daily dose of metformin (?1500 mg or max. tolerated dose) for at least 90 calendar days prior to screening - Body mass index (BMI) ? 40 kg/m^2 |
- Hombres o mujeres ? 18 años de edad en el momento de la firma del consentimiento informado. - Sujetos con diabetes mellitus tipo 2 (diagnosticada clínicamente) desde ? 6 meses antes de la selección - HbA1c del 7,0-10,0 % [53mmol/mol-86 mmol/mol] (ambos inclusive) según el análisis de laboratorio central - Tratamiento actual con IGlar durante al menos90 días naturales antes de la selección - Dosis diaria estable de IGlar comprendida entre 20 y 50 unidades (ambas inclusive) durante al menos 56 días naturales antes de la selección. La dosis diaria total deberá estar dentro del intervalo de 20 a 50 unidades, ambos inclusive, el día de la selección, si bien se aceptan fluctuaciones individuales del ± 10 % en los 56 días naturales anteriores a la selección. - Dosis diaria estable de metformina (? 1500 mg o dosis máxima tolerada) durante al menos 90 días naturales antes de la selección - Índice de masa corporal (IMC) ? 40 kg/m2 |
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E.4 | Principal exclusion criteria |
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 calendar days before screening - Anticipated initiation or change in concomitant medications in excess of 14 calendar days known to affect weight or glucose metabolism, such as weight loss/modifying (e.g.; sibutramine, orlistat, thyroid hormones, corticosteroids) - Impaired liver function, defined as alanine aminotransferase (ALT) ?2.5 times upper limit of normal - Renal impairment eGFR <60 mL/min/1.73 m^2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) - Screening calcitonin ?50 ng/L - History of pancreatitis (acute or chronic) - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 |
- 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 naturales antes de la selección - Previsión de inicio o modificación de tratamiento con medicamentos concomitantes durante más de 14 días naturales que se sabe que afectan al peso o al metabolismo de la glucosa, como pérdida o variación de peso (por ejemplo, sibutramina, orlistat, hormonas tiroideas, corticosteroides) - Disfunción hepática, definida como un valor de alanina aminotransferasa (ALT) ? 2,5 veces el límite superior de la normalidad. - Insuficiencia renal, FGe < 60 ml/min/1,73 m2 conforme a la ecuación del grupo CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) - Calcitonina de selección ? 50 ng/l - Antecedentes de pancreatitis (aguda o crónica) - Antecedentes personales o familiares de carcinoma medular de tiroides (CMT) o de neoplasia endocrina múltiple de tipo 2 (MEN2) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c |
Variación de la HbA1c con respecto al valor basal |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of treatment |
Tras 26 semanas de tratamiento |
|
E.5.2 | Secondary end point(s) |
1. Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes 2. Change from baseline in body weight 3. Responder for HbA1c (yes/no): - HbA1c < 7.0% - HbA1c ? 6.5% |
1. Número de episodios emergentes graves sin tratamiento o episodios hipoglucémicos sintomáticos confirmados mediante determinación de glucemia en sangre 2. Variación del peso corporal con respecto al valor basal 3. Respuesta de la HbA1c (sí/no): - HbA1c < 7,0 % - HbA1c ? 6,5 % |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. During 26 weeks of treatment 2. After 26 weeks of treatment 3. After 26 weeks of treatment |
1. Durante 26 semanas de tratamiento 2. Tras 26 semanas de tratamiento 3. Tras 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
European Union |
Israel |
Mexico |
Russian Federation |
Turkey |
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |