E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
type 2 diabetes |
diabete di tipo 2 |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10027433 - Metabolism and nutrition disorders |
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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. This is done by comparing the difference in change in HbA1c from baseline after 26 weeks of treatment to a noninferiority limit of 0.3% for insulin degludec/liraglutide vs insulin degludec and to a superiority limit of 0% for insulin degludec/liraglutide vs liraglutide |
Confermare l'efficacia di insulina degludec/liraglutide nel controllo glicemico del paziente diabetico di tipo 2. Cio' viene effettuato mettendo a confronto la differenza nel cambiamento del valore dell' HbA1c alla baseline e dopo 26 settimane di trattamento con un limite di non inferiorita' dello 0.3% per insulina degludec/liraglutide versus insulina degludec e con un limite di superiorita' dello 0% per l'insulina degludec/liraglutide versus liraglutide. |
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E.2.2 | Secondary objectives of the trial |
1 - To confirm superiority of insulin degludec/liraglutide vs insulin degludec after 26 weeks of treatment on either weight control, hypoglycaemic episodes, glycaemic control in relation to a meal, or glycaemic control as indirectly measured by daily dose of insulin degludec 2 - To compare general efficacy and safety of degludec/liraglutide, insulin degludec and liraglutide after 26 weeks of treatment - 3 - to confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in subjects with type 2 diabetes after 52 weeks of treatment. |
1- Confermare la superiorita` dell`insulina degludec/liraglutide versus insulina degludec dopo 26 settimane di trattamento sul controllo del peso,sugli episodi di ipoglicemia,il controllo glicemico in relazione ai pasti o il controllo glicemico misurato indirettamente dalla dose giornaliera di insulina degludec.2- Mettere a confronto l`efficacia e la sicurezza di insulina degludec/liraglutide,insulina degludec e liraglutide dopo 52 settimane di trattamento.- 3- confermare l`efficacia dell`insulina degludec/liraglutide nel controllo della glicemia in soggetti con diabete di tipo 2 dopo 52 settimane di trattamento. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
OTHER SUBSTUDIES:
See Addendum to protocol version 2.0 final date 15 Dec 2010.
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ALTRI SOTTOSTUDI:
Il sottostudio (Addendum al protocollo Versione 2.0 Final del 15 Dec 2010)prevede l`esecuzione del monitoraggio continuo del glucosio (CGM) e meal test per una sottopopolazione di pazienti.
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E.3 | Principal inclusion criteria |
Subjects with type 2 diabetes • HbA1c 7.0-10.0 % (both inclusive) with the aim of a median HbA1c of 8.3%. Accordingly, when approximately 50% of the randomised subjects have a HbA1c above 8.3%, the remaining subjects randomised must have a HbA1c of below or equal to 8.3%, or when approximately 50% of the randomised subjects have a HbA1c of below or equal to 8.3%, the remaining subjects randomised must have a HbA1c above 8.3% • Male or female, age 18 years or above • Subjects on stable dose of 1-2 OADs (metformin [`¥ 1500 mg or max tolerated dose] or metformin [`¥ 1500 mg or max tolerated dose] + pioglitazone [`¥ 30 mg]) for at least 90 days prior to screening • BMI `¤ 40 kg/m^2 |
1 - HbA1c 7.0-10.0 % (entrambi inclusi) con l'obiettivo di una mediana HbA1c di 8.3%. Quindi nel momento in cui circa il 50% dei soggetti randomizzati presenti valori di HbA1c sopra 8.3%, i rimanenti soggetti randomizzati presentereanno valori di HbA1c inferiori o uguali a 8.3%. Viceversa nel momento in cui il 50% di soggetti randomizzati presenti valori di HbA1c inferiori o uguali a 8.3%, la parte rimanente dei soggetti randomizzati presentera` valori di HbA1c superiori a 8.3%. 2 -Maschi o Femmine di eta` superiore ai 18 anni. 3 -Soggetti trattati con 1-2 OAD a dosaggio stabile (metformina [maggiore o uguale 1.500 mg o dose massima tollerata] o metformina [maggiore o uguale 1.500 mg o dose massima tollerata] + pioglitazone [maggiore o uguale 30 mg]) per almeno 90 giorni prima della screening. 4 - BMI inferiore o uguale 40 kg/m2 |
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E.4 | Principal exclusion criteria |
• Treatment with insulin (except for short-term treatment due to intercurrent illness at the discretion of the Investigator) • Treatment with GLP-1 receptor agonists (eg exenatide, liraglutide), sulphonylurea or dipeptidyl peptidase 4 (DPP-4) inhibitors within 90 days prior to trial • Impaired liver function, defined as alanine aminotransferese (ALAT) `¥ 2.5 times Upper Normal Range (UNR) (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive) • Impaired renal function defined as serum-creatinine `¥ 133 µmol/l (`¥ 1.5 mg/dl) for males and `¥ 125 µmol/l (`¥ 1.4) for females, or as allowed according to local contraindications for metformin (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive) • Screening calcitonin `¥ 50 ng/L • Subjects with personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2) • Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the last 12 months and planned coronary, carotid or peripheral artery revascularisation procedures • Severe uncontrolled treated or untreated hypertension (systolic blood pressure `¥ 180 mm Hg or diastolic blood pressure `¥ 100 mm Hg) • Acute treatment required proliferative retinopathy or maculopathy (macular oedema) • History of chronic pancreatitis or idiopathic acute pancreatitis |
1 - Trattamento con insulina (eccetto in caso di trattamenti a breve termine dovuti a malattie intercorrenti a discrezioen del medico) 2 - Trattamento con agonisti del recettore GLP-1 ( es. exenatide, liraglutide), sulfanilurea o inibitori della dipeptyl peptidasi 4 (DPP-4)entro 90 giorni prima dell`inizio dello studio. 3 - funzionalita` epatica compromessa, definita come alanina aminostrasferasi (ALAT)maggiore o uguale 2.5 volte il Range di Noralita` piu` alto (UNR)(e` permessa un`analisi re-test effettuata presso il laboratorio centrlizzato entro uan settimana dal primo campione prelevato. Il risultato dell`ultimo campione risultera` quello definitivo). 4 - Funzione renale compromessa definita come livelli di creatinina nel siero maggiore o uguale 133 µmol/l (maggiore o uguale 1.5 mg/dl) per gli uomini and maggiore o uguale 125 µmol/l (maggiore o uguale 1.4) per le donne, o secondo quando permesso dalle controindicazioni locali per il trattamento con metformina (e` permessa un`analisi re-test effettuata presso il laboratorio centrlizzato entro uan settimana dal primo campione prelevato. Il risultato dell`ultimo campione riusltera` quello definitivo) 5 - Livelli di calcitonina allo screening maggiore o uguale 50 ng/L 6 - soggetti con storia personale o familiare di carcinoma medullare della tiroide (MTC) o di neoplasia endocrina multipla di tipo 2 (MEN-2) 7 - disordini a livello Caridaco definiti come: Insufficienza cardiaca congestiva (NYHA classe III-IV), diagnosi di angina pectoris instabile, ischemia cerebrale e/o infarto del miocardio negli ultimi dodici mesi e la pianificazione di procedure di rivascolarizzazione delle coronarie, carotidi o arterie periferiche. 8 - Ipertensione grave trattata o non trattata (pressione sistolica maggiore o uguale 180 mm Hg o pressione diastolica maggiore o uguale 100 mm Hg) 9 - Retinopatia proliferativa che richieda trattamento acuto o maculopatia (edema maculare) 10 - Storia di pancreatite cronica o pancreatite acuta idiopatica. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baselinein HbA1c after 26 weeks of treatment. |
Cambiamento del valore di HbA1c dalla baseline dopo 26 settimane di trattamento. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 3 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | 7 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |