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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045234 |
E.1.2 | Term | Type I diabetes mellitus with other specified manifestations |
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 characterize insulin activity of Glargine U 100 vs insulin Glargine U 300, in subjects with type 1 diabetes in a setting of real life conditions, in order to transfer informations obtained with pharmacokinetic and pharmacodynamic studies into every day clinical practice. |
Obiettivo dello Studio ¿ quello di caratterizzare efficacia cinica ed attivit¿ glucodinamica di glargine U-300, nei confronti di glargine U-100, nel diabete Tipo 1, utilizzando dosi terapeutiche di insulina. Lo studio comprende una parte clinica, che verr¿ seguita da tutti i pazienti arruolati che si solger¿ su 6 mesi (3 mesi di intervento attivo per ciascun trattamento intervallati da 2 mesi di wash-out). |
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E.2.2 | Secondary objectives of the trial |
¿ Dose of insulin Gla-U300 vs Gla-U100.
¿ Risk for nocturnal hypoglycemia
¿ PK/PD and effects on lipid metabolism of Gla U-100 and Gla U-300
¿ Intra-subject variability of Gla U-300 vs Gla U-100, as calculated from day-to-day pre-dinner PG in the 3 month treatment, and CGM during last week 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
|
Un subset di pazienti andr¿ indagato anche con uno studio di farmacocinetica e farmacodinamica per valutare l¿attivit¿ dell¿insulina basale. Ulteriore osservazione sar¿ qualle ottenuta da un terzo subset di pazienti che varr¿ studiato con un test al digiuno di 12 ore, per verificare la durata di azione dell¿insulina basale, in un contesto pi¿ clinico, comunque standardizzato ma pi¿ vicino alle reali condizioni di vita del paziente. |
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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 10 may 2015 vers #1
Fast test 10 may 2015 vers #1
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: - Farmacocinetica e farmacodinamica.
- Test al digiuno
10 Maggio 2015, per entrambi; versione #1
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
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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 micro-macroangiopatiche, 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
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- 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 establish the non-inferiority of Gla-U300 to Gla-U100 in lowering pre-injection (pre-dinner) PG. |
Stabilire la non-inferiorità di Glargine U300 rispetto a Glargine U100 nella riduzione della glicemia prima dell'iniezione insulinica pre-cena |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the three months of treatment |
Alla fine del terzo mese di trattamento |
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E.5.2 | Secondary end point(s) |
¿ Dose of insulin Gla-U300 vs Gla-U100.
¿ Risk for nocturnal hypoglycemia
¿ PK/PD and effects on lipid metabolism of Gla U-100 and Gla U-300
¿ Intra-subject variability of Gla U-300 vs Gla U-100, as calculated from day-to-day pre-dinner PG in the 3 month treatment, and CGM during last week 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
|
¿ Durata di azione dell¿effetto insulinico
¿ Glicemia plasmatica
¿ Infusione di insulina durante la fase pre-clamp
¿ Infusione di glucosio
¿ Indice di fluttuazione
¿ Effetto insulinico sul metabolismo lipidico
¿ Variabilit¿ intra ed inter soggetto dell¿infusione di glucosio durante clamp
¿ Concentrazioni plasmatiche dei substrati non-glucidici
¿ Turnover del glucosio con stima della produzione epatica e dell¿utilizzazione periferica
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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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Medesimo prinicpio attivo formulato ad una diversa concentrazione |
Same drug with different concentration |
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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 |