E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type2-Diabetes |
Diabete Mellito di tipo II |
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E.1.1.1 | Medical condition in easily understood language |
Type2-Diabetes |
Diabete Mellito di tipo II |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 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 demonstrate non-inferiority of SAR342434 versus Humalog in glycated hemoglobin A1c (HbA1c) change from baseline to Week 26 in patients with type 2 diabetes mellitus (T2DM) also using insulin glargine |
Dimostrare la non inferiorità di SAR342434 rispetto a Humalog per quanto riguarda la variazione dei livelli di HbA1c alla settimana 26 rispetto al basale in pazienti con diabete mellito di tipo 2 trattati anche con insulina glargine |
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E.2.2 | Secondary objectives of the trial |
- To assess the immunogenicity of SAR342434 and Humalog in terms of positive/negative status and antibody titers at baseline and during the course of the study; -To assess the relationship of anti-insulin antibodies with efficacy and safety; - To assess the efficacy of SAR342434 and Humalog on: proportion of patients reaching target HbA1c <7.0% and ≤6.5%, fasting plasma glucose (FPG) and self-measured plasma glucose (SMPG) profiles, and insulin dose; - To assess safety of SAR342434 and Humalog.- To assess the immunogenicity of SAR342434 and Humalog in terms of positive/negative status and antibody titers at baseline and during the course of the study; -To assess the relationship of anti-insulin antibodies with efficacy and safety; - To assess the efficacy of SAR342434 and Humalog on: proportion of patients reaching target HbA1c <7.0% and ≤6.5%, fasting plasma glucose (FPG) and self-measured plasma glucose (SMPG) profiles, and insulin dose; - To assess safety of SAR342434 and Humalog. |
- Valutare l'immunogenicità di SAR342434 e di Humalog per quanto riguarda lo stato di positività o negatività e il titolo di anticorpi al basale e durante il corso dello studio; - Valutare la relazione tra lo sviluppo di anticorpi anti-insulina e l’efficacia e la sicurezza; - Valutare l'efficacia di SAR342434 e di Humalog su: quota di pazienti che raggiungono i livelli target di HbA1c (<7.0% e <6.5%); glicemia plasmatica a digiuno (FPG); profili della glicemia plasmatica automonitorata (SMPG); dose di insulina; - Valutare la sicurezza di SAR342434 e Humalog. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with T2DM diagnosed for at least 12 months and treated with insulin glargine and Humalog or NovoLog®/NovoRapid® (at least 3 times daily, before each meal) in the last 6 months prior to the screening visit; - Signed Written informed consent. |
- Pazienti con diabete mellito di tipo 2 diagnosticato da almeno 12 mesi e trattato con insulina glargine e Humalog o NovoLog®/NovoRapid® (almeno 3 volte al giorno prima di ogni pasto) nei sei mesi prima della visita di Screening; - Consenso informato scritto |
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E.4 | Principal exclusion criteria |
- At screening visit, age under legal age of adulthood; - HbA1c <6.5% or >10.0% at screening; - Diabetes other than T2DM; - Pregnancy and lactation; - Women of childbearing potential not protected by highly effective contraceptive method of birth control; - Use of insulin pump in the 6 months before screening visit; - Use of insulin other than insulin glargine and Humalog or NovoLog/NovoRapid in the 6 months prior to screening visit. Liprolog® is an EU approved insulin lispro and is allowed in those countries where it is marketed; - Use of Humalog or Novolog/NovoRapid less than 3 times daily, before each meal; - Use of non-injectable peptides (eg, GLP-1-receptor-agonists or other peptides) in the 6 months prior to screening visit; - Body mass index (BMI) ≥40kg/m² at screening visit; - Hospitalization for diabetic ketoacidosis in the last 6 months before screening visit; - Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (eg, laser, surgical treatment, or injectable drugs) during the study period. |
- Età inferiore alla maggiore età legale alla visita di Screening; - HbA1c <6,5% o >10% alla visita di screening; - Diabete diverso dal diabete mellito di tipo 2; - Gravidanza e allattamento; - Donne in età fertile che non fanno uso di un metodo contraccettivo efficace; - Uso di una pompa per insulina nei 6 mesi precedenti la visita di screening; - Uso di un'insulina diversa dall'insulina glargine e da Humalog o NovoLog/NovoRapid nei 6 mesi precedenti alla visita di screening; Liprolog® è una insulina lispro ed è consentito in quei paesi dove è commercializzato; - Uso di Humalog o di NovoLog/NovoRapid meno di 3 volte al giorno prima di ogni pasto; - Uso di peptidi iniettabili non insulinici (ad es. agonisti del recettore del GLP1 o altri peptidi) nei 6 mesi precedenti la visita di screening; - Indice di massa corporeo ≥ 40 Kg/m2 alla visita di screening; - Ricovero ospedaliero per chetoacidosi diabetica (DKA) nei 6 mesi precedenti la visita di screening; - Retinopatia diabetica proliferante instabile o qualsiasi altra retinopatia diabetica a rapida progressione o edema maculare che presumibilmente necessiterà di un trattamento (ad es. laser, trattamento chirurgico o medicinali iniettabili) durante il periodo di studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c |
Variazione dei livelli di HbA1c |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
from baseline to week 26 |
dal basale alla settimana 26 |
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E.5.2 | Secondary end point(s) |
1.Percentage of patients with HbA1c <7.0% and ≤6.5% 2.Change in FPG 3.Change in the mean 24-hour plasma glucose concentration, based on the 7-point Self Measured Plasma Glucose profile 4.Change in postprandial plasma glucose excursions (difference between 2 hour postprandial and pre-prandial plasma glucose values at breakfast, lunch, and dinner) 5.Number of patients with hypoglycemia event 6.Number of hypoglycemia events per patient 7.Number of patients with injection site reactions 8.Number of patients with hypersensitivity reactions 9.Number of patients with adverse events |
1.Percentuale di pazienti che raggiungono valori di HbA1c < 7% o ≤ 6,5%; 2.Variazione della FPG; 3.Variazione della concentrazione plasmatica media di glucosio nelle 24 ore, basata sul profilo SMPG a 7 punti; 4.Variazione delle escursioni della glicemia postprandiale (differenza tra i valori glicemici 2 ore dopo e prima dei pasti a colazione, pranzo e cena); 5.Numero di pazienti con eventi ipoglicemici 6.Numero di eventi ipoglicemici per paziente 7.Numero di pazienti con reazioni al sito di iniezione 8.Numero di pazienti con reazioni di ipersensibilità 9.Numero di pazienti con eventi avversi
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: at week 26 2, 3 and 4: from baseline to week 26 5, 6, 7, 8 and 9: up to 26 weeks |
1: alla settimana 26 2, 3 e 4: dal basale alla settimana 26 5, 6, 7, 8 e 9: fino alla settimana 26
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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 | 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 | 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 | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
Argentina |
Brazil |
Colombia |
Germany |
Hungary |
Italy |
Korea, Republic of |
Mexico |
Romania |
Russian Federation |
Spain |
Turkey |
United States |
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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 | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 1 |