E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes |
Diabete mellito, tipo 2 |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Diabete tipo 2 |
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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 | 21.1 |
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 |
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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 that oral semaglutide lowers the risk of major adverse cardiovascular events compared to placebo, both added to standard of care in patients with type 2 diabetes and at high risk of cardiovascular events. |
Dimostrare che semaglutide orale abbassa il rischio di eventi avversi cardiovascolari maggiori in confronto al placebo, in aggiunta alla terapia standard in pazienti con diabete tipo 2 e ad alto rischio cardiovascolare. |
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E.2.2 | Secondary objectives of the trial |
To compare the effects of oral semaglutide versus placebo, both added to standard of care in patients with type 2 diabetes and at high risk of cardiovascular events with regards to: -Chronic kidney disease -Cardiovascular events -Peripheral artery disease -Glycaemic control and body weight -Safety |
Confrontare gli effetti di semaglutide orale in confronto a placebo, in in aggiunta alla terapia standard in pazienti con diabete tipo 2 e ad alto rischio cardiovascolare rispetto a: -Malattia renale cronica -Eventi cardiovascolari -Malattia delle arterie periferiche -Controllo glicemico e peso corporeo -Sicurezza |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, age 50 years or older at the time of signing informed consent. 2. Diagnosed with type 2 diabetes mellitus 3. HbA1c 6.5% - 10.0% (47 - 86 mmol/mol) (both inclusive) (latest available and no more than 30 days old local laboratory assessment based on medical records or point of care measurement) 4. At least one of the below conditions (a-d): a) Coronary heart disease defined as at least one of the following: i. Prior myocardial infarction ii. Prior coronary revascularisation procedure iii. Equal to or above 50% stenosis in coronary artery documented by cardiac catheterisation, computerizede tomography coronary angiography iv. Coronary heart disease with ischaemia documented by stress test with any imaging modality b) Cerebrovascular disease defined as at least one of the following: i. Prior stroke ii. Prior carotid artery revascularisation procedure iii. Equal to or above 50% stenosis in carotid artery documented by X-ray angiography, magnetic resonance angiography, computerizede tomography angiography or Doppler ultrasound c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an Ankle-brachial index (ABI) < 0.85 at rest ii. Intermittent claudication with an equal to or above 50% stenosis in peripheral artery (excluding carotid) documented by X-ray angiography, magnetic resonance angiography, computerizede tomography angiography or Doppler ultrasound iii. Prior peripheral artery (excluding carotid) revascularization procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or osteomyelitis) d) Chronic kidney disease defined as: i. eGFR < 60 mL/min/1.73 m2 (Based on medical records using latest available and no more than 6 months old assessment). |
1.Pazienti di sesso maschile o femminile, età =50 anni al momento della firma del modulo di consenso informato 2.Diagnosi di diabete mellito tipo 2. 3. HbA1c compresa tra 6,5% e 10,0% (47-86 mmol/mol) (entrambi inclusi) (ultimo valore disponibile e non più vecchio di 30 giorni ottenuto tramite laboratorio locale o valore ottenuto tramite lo strumento point of care. 4. Almeno una delle seguenti condizioni (a-d): a) Cardiopatia coronarica, definita come la presenza di almeno una delle seguenti condizioni: i. Precedente infarto del miocardio ii. Precedente procedura di rivascolarizzazione coronarica iii. Stenosi =50% nell’arteria coronaria, documentata mediante cateterizzazione cardiaca o angiografia coronarica mediante TC [Tomografia computerizzata] iv. Cardiopatia coronarica con ischemia, documentata mediante test da sforzo con qualsiasi tecnica di diagnostica per immagini b) Malattia cardiovascolare definita come la presenza di almeno una delle seguenti condizioni: i. Precedente ictus ii. Precedente procedura di rivascolarizzazione carotidea iii. Stenosi =50% nell’arteria carotidea, documentata mediante angioradiografia, angiografia con RM [Risonanza magnetica], angiografia mediante tomografia computerizzata o EcoDoppler c) Arteriopatia periferica sintomatica (PAD), definita come la presenza di almeno una delle seguenti condizioni: i. Claudicatio intermittente con un indice caviglia-braccio (Ankle-Brachial Index, ABI) <0,85 a riposo ii. Claudicatio intermittente con una stenosi =50% nell’arteria periferica (esclusa la carotide), documentata mediante angioradiografia, angiografia con RM (Risonanza Magnetica), angiografia mediante tomografia computerizzata o EcoDoppler iii. Precedente procedura di rivascolarizzazione di un’arteria periferica (esclusa la carotide) iv. Amputazione di un arto inferiore a livello della caviglia o sopra la caviglia a causa di una malattia aterosclerotica (esclusi, ad esempio, traumi od osteomielite) d) Malattia renale cronica, definita come: i. eGFR <60 ml/min/1,73 m2 (Secondo quanto riportato nella cartella clinica in base all’ultima valutazione disponibile e non risalente a più di 6 mesi prima). |
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E.4 | Principal exclusion criteria |
1. Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack (TIA) within the past 60 days prior to the day of screening 2. Planned coronary, carotid or peripheral artery revascularisation. 3. Heart failure presently classified as being in New York Heart Association (NYHA) Class IV. 4. Treatment with any GLP-1 receptor agonist (RA) within 30 days before screening. |
1. Uno qualsiasi dei seguenti eventi: infarto miocardico, ictus, ricovero per angina pectoris instabile o attacco ischemico transitorio (TIA) nei 60 giorni precedenti il giorno dello screening. 2. Rivascolarizzazione pianificata delle arterie coronarie, carotidi o arterie periferiche. 3. Insufficienza cardiaca di Classe IV secondo la New York Heart Association (NYHA). 4. Trattamento con qualsiasi agonista del recettore (Receptor Agonist, RA) del GLP-1 [Glucagon-Like Peptide-1 (Peptide glucagone-simile 1)] nei 30 giorni precedenti lo screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first occurrence of MACE, a composite endpoint consisting of: -CV death -non-fatal myocardial infarction -non-fatal stroke. |
Tempo che intercorre fino al primo episodio MACE (endpoint composito espanso) costituito da: -Morte cardiovascolare -Infarto del miocardio non fatale -Ictus non fatale. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomisation (week 0) to end-of-trial (up to 61 months or more) (trial is event driven). |
Dalla randomizzazione (Settimana 0) al termine dello studio (fino a =61 mesi) (lo studio è event driven). |
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E.5.2 | Secondary end point(s) |
Time to first occurrence of a composite endpoint consisting of: -Cardiovascular death -Renal death -Onset of persistent = 50% reduction in eGFR (CKD-EPI) (compared with baseline) -Onset of persistent eGFR (CKD-EPI) < 15 mL/min/1.73 m2 -Initiation of chronic renal replacement therapy (dialysis or kidney transplantation); Time to occurrence of Cardiovascular Death; Time to first occurrence of major adverse limb events (MALE), a composite endpoint consisting of: -acute limb ischemia hospitalisation -chronic limb ischemia hospitalisation |
Tempo che intercorre fino al primo endpoint composito espanso costituito da: -Morte cardiovascolare -Morte renale -Comparsa di una riduzione persistente =50% nell’eGFR (CKD-EPI) (in confronto al baseline) -Comparsa di eGFR persistente (CKD-EPI) <15 ml/min/1,73 m2 -Inizio di una terapia di sostituzione renale cronica (dialisi o trapianto di rene); Tempo che intercorre fino al primo evento di decesso cardiovascolare; Tempo che intercorre fino al primo episodio di un evento avverso maggiore a carico degli arti (Major Adverse Limb Event, MALE), un endpoint composito costituito da: -Ricovero per ischemia acuta a carico degli arti -Ricovero per ischemia cronica a carico degli arti |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From randomisation (week 0) to end-of-trial (up to 61 months or more) (the trial is event driven).; From randomisation (week 0) to end-of-trial (up to 61 months or more) (the trial is event driven).; From randomisation (week 0) to end-of-trial (up to 61 months or more) (the trial is event driven). |
Dalla randomizzazione (Settimana 0) al termine dello studio (fino a =61 mesi) (lo studio è event driven); Dalla randomizzazione (Settimana 0) al termine dello studio (fino a =61 mesi) (lo studio è event driven); Dalla randomizzazione (Settimana 0) al termine dello studio (fino a =61 mesi) (lo studio è event driven) |
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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 | 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 | 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 | 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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 121 |
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 | Information not present in EudraCT |
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 |
Algeria |
Brazil |
Canada |
China |
Colombia |
Hong Kong |
India |
Israel |
Japan |
Korea, Democratic People's Republic of |
Malaysia |
Mexico |
Russian Federation |
South Africa |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
European Union |
Argentina |
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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
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 12 |