E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
type 1 diabetes mellitus |
diabete mellito tipo 1 |
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E.1.1.1 | Medical condition in easily understood language |
type 1 diabetes mellitus |
diabete mellito tipo 1 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 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 characterize insulin activity of Glargine U300 (Gla U300) vs insulin Degludec (Deg), in subjects with type 1 diabetes |
Obiettivo dello Studio ¿ quello di caratterizzare efficacia cinica ed attivit¿ glucodinamica di Glargine U-300, nei confronti di insulina Degludec, nel diabete Tipo 1 |
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E.2.2 | Secondary objectives of the trial |
safety (risk reduction of hypoglycemia), clinical efficacy, PD during clamp studies |
Safety (riduzione del rischio di ipoglicemia), efficacia clinica, farmacodinamica durante clamp |
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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 types of substudies Specify title, date and version of each substudy with relative objectives: PK-PD study vers 1 30/06/2016; Fast test study vers 1 30/06/2016 A first subset of subjects will be studied with the euglycemic clamp technique to evaluate pharmacokinetic and pharmacodynamic properties of basal insulins A second subset of subjects will undergo a fasting test study to establish duration of action of basal insulin independently of the clamp study, in real life conditions
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sotto-studio di farmacocinetica e farmacodinamica vers 1 del 30/06/2016; Sotto-studio test al digiuno vers 1 del 30/06/2016. Lo studio di farmacocinetica e farmacodinamica ¿ volto a valutare il profilo biologico dell'insulina basale da testare, utilizzando lo studio di clamp. Il test al digiuno valuta l'azione biologica dell'insulina in uno scenario clinico molto vicino alle condizioni reali di vita del paziente.
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E.3 | Principal inclusion criteria |
Subjects meeting all of the following criteria will be considered for admission to the study: •Aged between 18 and 65 years •Type 1 diabetes mellitus for more than five years •Glycohemoglobin A1C >6.5 and < 8.5 % at visit 1 •Normal laboratory values, ECG, and vital signs unless the investigator considered an abnormality to be clinically irrelevant •Women postmenopausal or using contraception judged by the investigator to be adequate (e.g., oral contraceptives, intra-uterine device or surgical treatment), with a negative serum pregnancy test at visit 1 and negative urine pregnancy tests at study day (clamp visits) •No demonstrable micro- and macro-angiopathic complications. •On long-term intensive therapy with glargine as basal insulin. •Body mass index of between 20 and 27 kg/m2 |
Pazienti affetti da diabete mellito Tipo 1 (18-65 anni), in trattamento insulinico multi-iniettivo con insulina glargine, durata di malattia non inferirore a 5 anni, con emoglobina glicosilata > 6.5 <8.5%, BMI 20-27 kg/m 2, esenti da complicanze micromacroangiopatiche, malattie cardiovascolari, epatiche e cronico-degenerative. |
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria will not to be included in the study: •Diabetes other than type 1 diabetes mellitus •Type 1 diabetic subjects with total insulin dose of 1 IU/kg/day. •More than one episode of severe hypoglycaemia involving seizure or coma during the past year •Clinically relevant cardiovascular, hepatic, neurologic, endocrine or other major systemic diseases other than type 1 diabetes mellitus which could hinder implementation of the clinical study protocol or interpretation of the study results •History of demonstrable micro- and macro-angiopathic complications •Pregnancy and lactation •History of hypersensitivity to the study medication or to drugs with similar chemical structures •Likelihood of requiring treatment during the study period with any antidiabetic drug other than the drugs to be administered during the study •Progressive fatal diseases •History of drug or alcohol abuse |
- Altre forme di diabete oltre il tipo 1; - Diabete tipo 1 richiedente dosi elevate di insulina > 1 IU/kg/day. - Episodi pregressi di ipoglicemia severa nell'ultimo anno - Comorbilità rilevanti (cardiovascolare, epatiche, neurologiche e renali) - Rilevanti complicanze micoangiopatiche - Gravidanza e allattamento - Abuso di alcool o dipendenza da droghe |
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E.5 End points |
E.5.1 | Primary end point(s) |
to confirm the non-inferiority of insulin Gla-U300 to insulin Deg in reduction in HbA1c from baseline after three months of treatment. |
non inferiorità di efficacia di glargine U300 rispetto a Degludec (riduzione dell'emoglobina glicosilata) |
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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) |
¿ Dose of insulin Gla-U300 vs Deg ¿ Risk for nocturnal hypoglycemia Gla-U300 vs Deg ¿ PK/PD and effects on lipid metabolism of Gla U-300 and Deg ¿ Intra-subject variability of Gla U300 vs Deg, as calculated from day-to-day pre-dinner PG in the 3 month treatment, and CGM during last two sweek of treatment (also fasting/post-meal PG variability will be calculated); ¿ Intra-subject variability will be also assessed in the PK/PD study and correlated with the above reported clinical variability
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variabilit¿ glicemica, riduzione del rischio di ipoglicemia notturna, dosi insuliniche, riduzione del peso corporeo, area sotto la curva di GIR durante studio di clamp |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | Information not present in EudraCT |
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |