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 |
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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 the efficacy of insulin degludec/liraglutide in controlling glycaemia in subjects with type 2 diabetes mellitus (T2DM) on previous treatment with insulin glargine.
This is done by comparing the difference in change in glycosylated haemoglobin (HbA1c) from baseline after 26 weeks of treatment to a non-inferiority limit of 0.30% for insulin degludec/liraglutide vs insulin glargine. |
Confirmar la eficacia de insulina degludec/liraglutida para el control de la glucemia en sujetos con diabetes mellitus de tipo 2 (DMT2) en tratamiento previo con insulina glargina. Para ello se comparará la diferencia en la variación de la hemoglobina glucosilada (HbA1c) con respecto al valor basal después de 26 semanas de tratamiento, con un límite de no inferioridad del 0,30% para insulina degludec/liraglutida frente a insulina glargina. |
|
E.2.2 | Secondary objectives of the trial |
? To confirm superiority of insulin degludec/liraglutide versus insulin glargine after 26 weeks of treatment on one or more of the following: o Change from baseline in HbA1c o Confirmed hypoglycaemia o Change from baseline in body weight ? To compare safety of insulin degludec/liraglutide to insulin glargine after 26 weeks of treatment |
? Confirmar la superioridad de insulina degludec/liraglutida frente a insulina glargina después de 26 semanas de tratamiento en cuanto a uno o varios de estos parámetros: o Variación de la HbA1c con respecto al valor basal o Hipoglucemia confirmada o Variación del peso corporal con respecto al valor basal ? Comparar la seguridad de insulina degludec/liraglutida y de insulina glargina después de 26 semanas de tratamiento |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Type 2 diabetes mellitus ? ?18 years of age ? HbA1c 7.0-10.0% [53-86 mmol/mol] (both inclusive) by central laboratory analysis ? Current treatment with insulin glargine for at least 90 days prior to screening ? Stable daily dose of insulin glargine between 20 units and 50 units (both inclusive) for at least 56 days prior to screening. Total daily dose should be within the range of 20-50 units, both inclusive, on the day of screening, but individual fluctuations of ± 10% within the 56 days prior to screening are acceptable. ? Stable daily dose of metformin (? 1500 mg or max tolerated dose) for at least 90 days prior to screening ? Body mass index (BMI) ?40 kg/m^2 |
? Diabetes mellitus de tipo 2 ? ? 18 años de edad ? HbA1c del 7,0-10,0% [53-86 mmol/mol] (ambos inclusive) según el análisis de laboratorio central ? Tratamiento activo con insulina glargina durante 90 días como mínimo antes de la selección ? Dosis diaria estable de insulina glargina entre 20 y 50 unidades (ambas inclusive) durante como mínimo 56 días antes de la selección. La dosis diaria total deberá estar dentro del intervalo de 20-50 unidades, ambos inclusive, el día de la selección, si bien se aceptan fluctuaciones individuales de ± 10% en los 56 días anteriores a la selección. ? Dosis diaria estable de metformina (? 1500 mg o dosis máxima tolerada) durante 90 días como mínimo antes de la selección ? Índice de masa corporal (IMC) ? 40 kg/m2 |
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E.4 | Principal exclusion criteria |
? Any use of oral antidiabetic agents (OADs) (except for metformin) within 90 days prior to Visit 1 (screening) ? Current use of any drug (except metformin and insulin glargine) or anticipated change in concomitant medication, which in the investigator?s opinion could interfere with the glucose metabolism (e.g. systemic corticosteroids) ? Previous and/or current treatment with any insulin regimen other than basal insulin, e.g. prandial or pre-mixed insulin (short term treatment due to intercurrent illness including gestational diabetes is allowed at the discretion of the investigator) ? Previous and/or current treatment with glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exenatide, liraglutide) ? Impaired liver function, defined as ALAT ?2.5 times upper normal range (UNR) ? Impaired renal function defined as serum-creatinine ?133?mol/L (?1.5 mg/dL) for males and ?125 ?mol/L (1.4 mg/dL) for females, or as allowed according to local contraindications for metformin ? Screening calcitonin ?50 ng/L ? Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2) ? History of chronic pancreatitis or idiopathic acute pancreatitis |
? Tratamiento con antidiabéticos orales (ADO) (a excepción de metformina) en los ?90 días anteriores a la visita 1 (selección) ? Uso actual de cualquier fármaco (excepto metformina e insulina glargina) o cambio previsto de la medicación concomitante que, en opinión del investigador, pueda afectar al metabolismo de la glucosa (p. ej., corticosteroides sistémicos) ? Tratamiento previo o actual con cualquier tipo de insulina, excepto insulina basal, p. ej., insulina prandial o premezclada (se permite el tratamiento a corto plazo debido a una enfermedad intercurrente, como diabetes gravídicagestacional, a criterio del investigador) ? Tratamiento previo o actual con agonistas del receptor del péptido glucagonoide 1 (GLP-1) (por ejemplo, exenatida o liraglutida) ? Disfunción hepática, definida como un valor de ALAT ? ?2,5 veces el límite superior de la normalidad (LSN) ? Disfunción renal, definida como un valor de creatinina sérica ? 133 ?mol/l (? 1,5 mg/dl) en los varones y ??125 ?mol/l (1,4 mg/dl) en las mujeres, o con arreglo a las contraindicaciones de metformina en cada país ? Calcitonina ? ?50 ng/l en la selección ? Antecedentes personales o familiares de carcinoma medular de tiroides (CMT) o de neoplasia endocrina múltiple de tipo 2 (MEN2) ? Antecedentes de pancreatitis crónica o pancreatitis aguda idiopática |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c |
Cambio en la HbA1c 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. Change from baseline in body weight 2. Number of treatment emergent confirmed hypoglycaemic episodes |
? Variación del peso corporal con respecto al valor basal después de 26 semanas de tratamiento ? Número de episodios hipoglucémicos confirmados surgidos |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 26 weeks of treatment 2. During 26 weeks of treatment |
1. Tras 26 semanas de tratamiento 2. 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 | 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 | 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 | 34 |
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 |
Argentina |
Australia |
Brazil |
Mexico |
Russian Federation |
South Africa |
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 | 1 |
E.8.9.1 | In the Member State concerned days | 9 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 9 |