E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Diabete Mellito di tipo 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Diabete Mellito di tipo 2 |
|
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 | 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 that treatment with semaglutide does not result in an unacceptable increase in cardiovascular risk as compared to a pooled comparator group (including placebo and active comparators) in adults with type 2 diabetes. This is done by demonstrating that the upper limit of the 95% confidence interval (CI) of the hazard ratio for semaglutide versus comparators is less than 1.8 when comparing in a meta-analysis time to first occurrence of a major adverse cardiovascular event (MACE) using all MACEs accrued from all subjects included in all of the confirmatory phase 3a clinical trials. |
Confermare che il trattamento con semaglutide, confrontato con
un gruppo di confronto misto (che include placebo e comparatori attivi), non comporti un aumento inaccettabile del rischio cardiovascolare in pazienti adulti con diabete di tipo 2.
Questo verrà effettuato dimostrando che il limite superiore del 95% dell'intervallo di confidenza di hazard ratio tra semaglutide e i comapratori sia inferiore a 1.8 quando comparato in una meta analisi del tempo di insorgenza del primo evento cardiovascolare maggiore (MACE), utilizzando tutti gli eventi MACE registrati per tutti i pazienti inclusi in tutti gli studi clinici di fase 3a. |
|
E.2.2 | Secondary objectives of the trial |
To assess the long-term safety and efficacy of semaglutide 0.5 mg and 1.0 mg once weekly compared to placebo, both added on to standard of care, in adults with type 2 diabetes at high risk for cardiovascular events. |
Testare l'efficacia e la sicurezza a lungo termine di semaglutide in
somministrazione settimanale (0,5 mg e 1,0 mg)in confronto con
placebo, anche in aggiunta alla terapia standard (standard of care), in pazienti adulti con diabete di tipo 2 ad alto
rischio cardiovascolare. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men and women with type 2 diabetes mellitus.
- Age ≥50 years at screening and clinical evidence of cardiovascular disease or age ≥60 years at screening and subclinical evidence of cardiovascular disease.
- Anti-diabetic drug naïve, or treated with one or two OAD(s), or treated with human NPH insulin or long-acting insulin analogue or pre-mixed insulin, both types of insulin either alone or in combination with one or two OAD(s).
- HbA1c ≥7.0% at screening. |
Uomini e donne con diabete di tipo 2 -Età 50 anni allo screening con evidenze cliniche di patologie cardiovascolari oppure età 60 anni allo screening con evidenze sub-cliniche di patologie cardiovascolari. -pazienti che non hanno mai assunto farmaci antidibetici, oppure trattati con uno o due antidiebetici orali, oppure trattati con insulina umana NPH o analoghi insulinici a ad azione prolungata o insuline premiscelate, con sola terapia insulinica o associata ad uno o due antidibetici orali. -HbA1c > o uguale al 7% allo screening. |
|
E.4 | Principal exclusion criteria |
- Type 1 diabetes mellitus.
- Use of GLP-1 receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening.
- Use of any DPP-IV inhibitor within 30 days prior to screening.
- Treatment with insulin other than basal and pre-mixed insulin within 90 days prior to screening - except for short-term use in connection with intercurrent illness.
- Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (eg diabetes ketoacidosis) within 90 days prior to screening.
- History of chronic pancreatitis or idiopathic acute pancreatitis.
- An acute coronary or cerebro-vascular event within the previous 14 days from Visit 2.
- Currently planned coronary, carotid or peripheral artery revascularisation.
- Chronic heart failure NYHA class IV.
- Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma.
- Personal history of non-familial medullary thyroid carcinoma.
- Screening calcitonin ≥50 ng/L. |
Diabete di tipo1 - Uso di agonisti del recettore GLP-1 (exenatide,
liraglutide o altri) o pramlintide nei 90 giorni precedenti lo screening - Uso di qualsiasi inibitore DPP-IV nei 30 giorni precedenti lo screening. - Trattamento con insuline diverse dalla basale o dalla premiscelata nei 90 giorni precedenti lo screening, eccetto per uso a breve termine per patologie concomitanti. - Scompenso glicemico acuto che richieda un'immediata intensificazione del trattamento per prevenire complicanze acute del diabete (chetoacidosi diabetica) nei 90 giorni precedenti lo screening - Storia di pancreatite cronica o pancreatite acuta idiopatica - Un evento coronarico o cerebro-vascolare acuto nei 14 giorni precedenti la visita 2 - Eventi di rivascolarizzazione coronarica, carotidea o periferica programmati. - Scompenso cardiaco cronico di classe NYHA IV. - Storia personale o familiare di neoplasia endocrina multipla di tipo2 (MEN2) o storia familiare di carcinoma midollare della tiroide - Storia personale di carcinoma midollare della tiroide non familiare - Calcitonina 50 ng/L allo screening |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time from randomisation to first occurrence of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. |
Tempo dalla randomizzaione al prirmo evento cardiovascolare maggiore (MACE), definito come morte cardiovascolare, infarto del miocardio non fatale o ictus non fatale. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time from randomisation to first occurrence of a major adverse cardiovascular event (MACE). |
Tempo trascorso dalla randomizzazione al primo evento cardiovascolare maggiore (MACE). |
|
E.5.2 | Secondary end point(s) |
1 - Time from randomisation to first occurrence of an expanded composite cardiovascular outcome.
2 - Time from randomisation to each individual component of the expanded composite cardiovascular outcome.
3 - Change from baseline to last assessment during the treatment period in other treatment outcomes, including HbA1c, fasting plasma glucose, body weight, lipid profile, urinary albumin to creatinine ratio, vital signs, hypoglycaemic events, adverse events, antisemaglutide antibodies and patient reported outcome (PRO). |
1 - Tempo trascorso dalla randomizzazione al primo esito
cardiovascolare composito esteso.
2 - Tempo trascorso dalla randomizzazione alla comparsa di ciascun
componente individuale dell'esito cardiovascolare composito esteso.
3 - Cambiamenti rispetto alla baseline fino
all'ultima valutazione durante il periodo di trattamento in altri risultati del trattamento inclusa l'HbA1c, la glicemia a digiuno, il peso, il profilo lipidico, il rapporto albumina/creatinina nelle urine, segni vitali, eventi ipoglicemici, eventi avversi, anticorpi contro al semaglutide e i patient recorded outcome (PRO - questionari) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time from randomisation up to end of Follow-up (up to max. 148 weeks)
2. Time from randomisation up to end of Follow-up (up to max. 148 weeks)
3. From randomisation to end of treatment (up to max. 143 weeks)
|
- Tempo trascorso dalla randomizzaizone fino alla fine del follow up (massimo 148 settimane)
2 - Tempo trascorso dalla randomizzaizone fino alla fine del follow up (massimo 148 settimane)
3 - Tempo trascorso dalla randomizzaizone fino alla fine del trattamento (massimo 143 settimane) |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Evaluation of cardiovascular outcome |
Valutazione degli esiti cardiovascolari |
|
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 | Yes |
E.8.2.3.1 | Comparator description |
Two different doses of test IMP |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
European Union |
Algeria |
Argentina |
Australia |
Brazil |
Canada |
India |
Israel |
Malaysia |
Mexico |
Russian Federation |
Taiwan |
Thailand |
Turkey |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 15 |