E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 1 |
Diabete Mellito di tipo 1 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 1 diabetes |
Diabete di 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 |
|
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. |
Confermare la superiorità di liraglutide in confronto con
placebo nel controllo glicemico, in entrambi in aggiunta al trattamento con insulina,
dopo 26 settimane di trattamento in soggetti con diagnosi di diabete di tipo 1 in
controllo glicemico inadeguato. |
|
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. Confermare la superiorità di liraglutide in confronto con
placebo, entrambi in aggiunta al trattamento con insulina, sulla perdita di peso
corporeo dopo 26 settimane di trattamento in soggetti con diagnosi di diabete di tipo 1
con un inadeguato controllo glicemico.
2. Valutare la sicurezza e la tollerabilità di liraglutide in
confronto con placebo, entrambi in aggiunta al trattamento con insulina, durante 26
settimane di trattamento in soggetti con diabete di tipo 1 con un inadeguato controllo
glicemico. |
|
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. Consenso informato ottenuto prima di qualsiasi attività correlata allo studio. Per
attività correlate allo studio s’intende qualsiasi procedura svolta all’interno dello
studio, incluse le attività richieste per stabilire l’idoneità a partecipare dei
pazienti.
2. Uomini o donne con età ≥ a 18 anni al momento della firma del consenso
informato.
3. Diabete mellito di tipo 1 (diagnosticato clinicamente) da ≥ 12 mesi prima della
visita 1 (visita di screening).
4. Trattamento basal-bolus o con CSII (continuous subcutaneous insulin infusion)
da ≥ 6 mesi dalla visita 1.
5. Trattamento stabile con insulina ≥ 3 mesi prima della visita 1 (visita di
screening), valutato e documentato dallo sperimentatore.
6. Valori di HbA1c fra 7.0-10.0 %, estremi inclusi (Controllo del Diabete e studio
delle complicanze (DCCT)), analizzati dal laboratorio centrale (visita 1,
screening) e corrispondenti a 53-86 mmol/mol (Federazione Internazionale della
Clinica Chimica (IFCC)) |
|
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. Precedente uso di agonisti del recettore del GLP-1 o di inibitori del DDP- IV
2. Uso di qualsiasi farmaco che secondo lo sperimentatore può interferire con il
controllo glicemico (es. corticosteroidi sistemici) o con influire sulla sicurezza del
soggetto. Non è permessa l’insulina premiscelata.
3. Accertata retinopatia proliferativa o maculopatia che necessiti trattamento
acuto.
4. Neuropatia severa, in particolare neuropatia autonoma, es. gastroparesi, a
giudizio dello sperimentatore.
5. Pressione sanguigna incontrollata/non trattata allo screening (visita 1)(dopo una
attesa di 5 minuti) > di 160 mmHg per la sistolica e > di 100 mmHg per la distolica
durante la seduta (è permesso ripetere la misurazione a visita 2 (prima di effettuare le
attività connesse allo studio) per escludere ipertensione da camice-bianco
6. Storia di pancreatite cronica o acuta.
7. Valore di Calcitonina allo screening (visita 1) ≥ 50 ng/L.
8. Storia familiare o personale di carcinoma midollare della tiroide o neoplasia
endocrina multipla di tipo 2 (MEN 2).
9. Diagnosi di neoplasie maligne entro gli ultimi 5 anni(ad eccezione del carcinoma
delle cellule basali o squamose della pelle). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in glycosylated haemoglobin (HbA1c) |
Variazione del valore iniziale dell’emoglobina glicata (HbA1c) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of treatment |
Dopo 26 settimane di trattamento. |
|
E.5.2 | Secondary end point(s) |
1. Change from baseline in body weight
2. Number of treatment-emergent symptomatic hypoglycaemic episodes |
1. Variazione dal valore di partenza del peso corporeo
2. Numero di episodi ipoglicemici sintomatici in seguito al trattamento |
|
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. Dopo 26 settimane di trattamento
2. Durante le 26 settimane di trattamento |
|
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 |
Tollerabilità |
|
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 | 8 |
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 |
Ultima visita ultimo soggetto |
|
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 |