E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 1 |
Diabetes Mellitus Tipo 1 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 1 diabetes |
Diabetes tipo 1 |
|
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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I 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 liraglutide compared to placebo, both adjunct to insulin treatment, on glycaemic control, after 26 weeks of treatment in subjects with established type 1 diabetes in inadequate glycaemic control. |
Confirmar la superioridad de liraglutida en comparación con placebo, ambos administrados de forma adyuvante al tratamiento con insulina, en el control de la glucemia tras 26 semanas de tratamiento en pacientes diagnosticados con diabetes tipo 1 que presentan un control glucémico insuficiente. |
|
E.2.2 | Secondary objectives of the trial |
1. To confirm superiority of liraglutide compared to placebo, both adjunct to insulin treatment, with regards to body weight loss after 26 weeks of treatment in subjects with established type 1 diabetes in inadequate glycaemic control. 2. To evaluate safety and tolerability of liraglutide compared to placebo, both adjunct to insulin treatment, during 26 weeks of treatment in subjects with type 1 diabetes in inadequate glycaemic control. |
1. Confirmar la superioridad de liraglutida en comparación con placebo, ambos administrados de forma adyuvante al tratamiento con insulina, en relación con la pérdida de peso tras 26 semanas de tratamiento en pacientes diagnosticados con diabetes tipo 1 que presentan un control glucémico insuficiente. 2. Evaluar la seguridad y la tolerabilidad de la liraglutida en comparación con placebo, ambos administrados de forma adyuvante al tratamiento con insulina, durante 26 semanas de tratamiento en sujetos con diabetes tipo 1 que presentan un control glucémico insuficiente. |
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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, aged ? 18 years at the time of signing informed consent 3. Type 1 diabetes mellitus (as diagnosed clinically) ? 12 months prior to Visit 1 (i.e. screening) 4. Treatment with basal bolus or CSII (continuous subcutaneous insulin infusion, insulin pump) treatment ? 6 months prior to Visit 1 (i.e. screening) 5. Stable insulin treatment ? 3 months prior to Visit 1 (i.e. screening), as judged and documented by the investigator 6. HbA1c 7.0?10.0 % (Diabetes Control and Complications Trial (DCCT)), both inclusive, by central laboratory analysis (Visit 1, screening) corresponding to 53?86 mmol/mol (International Federation of Clinical Chemistry (IFCC)) |
1. Obtención del consentimiento informado antes de realizar cualquier actividad relacionada 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 mismo. 2. Pacientes de ambos sexos de ? 18 años de edad en el momento de la firma del consentimiento informado. 3. Diabetes mellitus tipo 1 (diagnosticada clínicamente) ? 12 meses antes de la visita 1 (es decir, selección). 4.Tratamiento con bolo basal o ISCI (infusión subcutánea continua de insulina, bomba de insulina) ? 6 meses antes de la visita 1 (es decir, selección). 5.Tratamiento estable con insulina ? 3 meses antes de la visita 1 (es decir, selección), evaluada y documentada por el investigador. 6. HbA1c de 7,0-10,0% (Diabetes Control and Complications Trial, DCCT), ambos inclusive, en el análisis del laboratorio central (visita 1, selección), que corresponde a 53-86 mmol/mol (International Federation of Clinical Chemistry, IFCC). |
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E.4 | Principal exclusion criteria |
1. Prior use of glucagon-like peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase IV (DPPIV) inhibitors 2. Use of any medication, which in the investigator?s opinion could interfere with the glycaemic control (e.g. systemic corticosteroids, pramlintide (Symlin®)) or affect the subject?s safety. Premix insulin is not allowed 3. Known proliferative retinopathy or maculopathy requiring acute treatment 4. Severe neuropathy, in particular autonomic neuropathy, i.e. gastroparesis, as judged by the investigator 5. Uncontrolled/ untreated blood pressure at screening (Visit 1) (after resting for 5 min) while sitting > 160 mmHg for systolic or >100 mmHg for diastolic (repeated measurement at Visit 2 (prior to performing the trial related activities) is allowed to exclude white-coat hypertension) 6. History of acute or chronic pancreatitis 7. Screening (Visit 1) calcitonin value ? 50 ng/L 8. Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) 9. Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer) |
1. Uso previo de agonistas de los receptores del péptido glucagonoide tipo 1 (GLP-1) o de inhibidores de la dipeptidil peptidasa IV (DPP-IV). 2. Uso de cualquier medicamento que, en opinión del investigador, podría interferir en el control de la glucemia (por ejemplo, corticosteroides sistémicos, pramlintida [Symlin®]) o afectar a la seguridad del sujeto. No se permite el uso de insulina premezclada. 3. Maculopatía o retinopatía proliferativa conocida que requiere tratamiento agudo. 4. Neuropatía grave, en particular neuropatía vegetativa, es decir, gastroparesia, según el criterio del investigador. 5. Presión arterial no controlada/no tratada en la visita de selección (visita 1) (después de 5 min de reposo) en sedestación > 160 mm Hg de presión sistólica o > 100 mm Hg de presión diastólica (se permite repetir la determinación en la visita 2 [antes de realizar las actividades relacionadas con el estudio] para descartar una "hipertensión de bata blanca"). 6. Antecedentes de pancreatitis aguda o crónica. 7. Valor de calcitonina ? 50 ng/l en la visita de selección (visita 1). 8. Antecedentes personales o familiares de carcinoma medular de tiroides o de síndrome de neoplasias endocrinas múltiples tipo 2 (MEN 2). 9. Diagnóstico de neoplasia maligna en los 5 años previos (excepto cáncer de piel basocelular o espinocelular) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in glycosylated haemoglobin (HbA1c) |
Variación de la hemoglobina glucosilada (HbA1c) con respecto al valor basal |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of treatment |
Después de 26 semanas de tratamiento |
|
E.5.2 | Secondary end point(s) |
1. Change from baseline in body weight 2. Number of treatment-emergent symptomatic hypoglycaemic episodes |
1.Variación del peso corporal con respecto al valor basal 2. Número de episodios de hipoglucemia sintomática |
|
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. Después de 26 semanas de tratamiento. 2. Durante el periodo de 26 semanasde tratamiento |
|
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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 92 |
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 |
Canada |
European Union |
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
|
LVLS |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 14 |