E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
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 compare the effect of once-daily dosing of 14 mg oral semaglutide versus 25 mg empagliflozin, both in combination with metformin, on glycaemic control in subjects with type 2 diabetes mellitus |
L’obiettivo primario è confrontare l’effetto del trattamento giornaliero di semaglutide 14 mg rispetto a empagliflozin 25 mg entrambi in combinazione con metformina, sul controllo glicemico in soggetti affetti da diabete mellito tipo 2. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the effect of once-daily dosing of 14 mg oral semaglutide versus 25 mg empagliflozin, both in combination with metformin, on body weight in subjects with type 2 diabetes mellitus.
2. To compare the safety and tolerability of once-daily dosing of 14 mg oral semaglutide versus 25 mg empagliflozin, both in combination with metformin, in subjects with type 2 diabetes mellitus
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Gli obiettivi secondari sono: - Confrontare l’effetto del trattamento giornaliero di semaglutide 14 mg rispetto ad empagliflozin 25 mg, entrambi in combinazione con metformina, sul peso corporeo in soggetti affetti da diabete mellito di tipo 2. - Confrontare la sicurezza e la tollerabilità del trattamento giornaliero di semaglutide 14 mg rispetto a empagliflozin 25 mg, entrambi in combinazione con metformina, in soggetti affetti da diabete mellito di tipo 2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. 2. Male or female, age above or equal to 18 years at the time of signing informed consent. 3. Diagnosed with type 2 diabetes mellitus = 90 days prior to day of screening. 4. HbA1c of 7.0-10.5 % (53-91 mmol/mol) (both inclusive). 5. Stable daily dose of metformin (= 1500 mg or maximum tolerated dose as documented in the subject medical record) = 90 days prior to the day of screening.
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1. Consenso informato ottenuto prima di qualsiasi attività correlata allo studio. Per attività correlate allo studio si intende qualunque procedura effettuata nell’ambito dello studio, incluse le attività per stabilire l’idoneità a partecipare. 2. Soggetti di sesso maschile o femminile, con almeno 18 anni di età al momento della firma del modulo di consenso informato. 3. Soggetti a cui è stato diagnosticato il diabete mellito tipo 2 da almeno 90 giorni prima del giorno dello screening. 4. HbA1c compresa tra 7,0 -10,5 % (53 - 91 mmol/mol) (inclusi). 5. Dose giornaliera stabile di metformina (= 1.500 mg o dose massima tollerata come documentato nella cartella clinica del soggetto) da almeno 90 giorni prima del giorno dello screening.
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E.4 | Principal exclusion criteria |
1. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). For certain specific countries: Additional specific requirements apply. 2. Any disorder, which in the investigator’s opinion might jeopardise subject’s safety or compliance with the protocol. 3. Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma. 4. History of pancreatitis (acute or chronic). 5. History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery). 6. Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening. 7. Subjects presently classified as being in New York Heart Association Class IV. 8. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening. 9. Subjects with ALT > 2.5 x upper normal limit. 10. Renal impairment defined as Estimated Glomerular Filtration Rate < 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). 11. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of = 14 days. 12. Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation. 13. History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ). 14. History of diabetic ketoacidosis.
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1. Paziente di sesso femminile in gravidanza, in allattamento, o che intenda iniziare una gravidanza o sia in età fertile e non utilizzi un metodo contraccettivo adeguato (misure contraccettive adeguate come richiesto dalla legge o dalla prassi locale). 2. Qualsiasi disturbo che, a giudizio dello sperimentatore, potrebbe mettere a rischio la sicurezza del soggetto o la compliance al protocollo. 3. Storia famigliare o personale di neoplasia endocrina multipla di tipo 2 (multiple endocrine neoplasia type 2, MEN 2) o carcinoma midollare della tiroide (Medullary Thyroids Carcinoma, MTC). 4. Storia di pancreatite (acuta o cronica). 5. Storia di interventi chirurgici maggiori che coinvolgono lo stomaco o che influiscono potenzialmente sull’assorbimento del prodotto sperimentale (ad es. gastrectomia parziale o totale, gastrectomia a manica, intervento di bypass gastrico). 6. Uno qualsiasi dei seguenti eventi: infarto del miocardio, ictus o ricovero in ospedale per angina instabile o per attacco ischemico transitorio nei 180 giorni precedenti lo screening. 7. Soggetti attualmente classificati nella classe IV della NYHA (New York Heart Association). 8. Procedure di rivascolarizzazione arteriosa periferica, carotidea o coronarica, pianificate già il giorno dello screening. 9. Soggetti con alanina aminotransferasi (ALT) superiore a 2,5 volte il limite superiore della norma (Upper Normal Limit, UNL). 10. Insufficienza renale definita come velocità di filtrazione glomerulare stimata per insufficienza renale (Glomerular Filtration Rate, eGFR) < 60 ml/min/1,73 m2 in base alla formula CKD-EPI(Chronic Kidney Disease Epidemiology Collaboration). 11. Trattamento con qualsiasi farmaco indicato per il diabete o l’obesità, diverso da quelli stabiliti nei criteri di inclusione, nel periodo dei 90 giorni precedenti lo screening. Fa eccezione il trattamento insulinico di breve termine per malattia acuta per un totale di = 14 giorni. 12. Retinopatia proliferativa o maculopatia che necessita di trattamento acuto, verificata per mezzo di fotografia del fondo oculare o fundoscopia per dilatazione eseguita entro i 90 giorni precedenti la randomizzazione. 13. Diagnosi o storia di neoplasie maligne negli ultimi 5 anni (fatta eccezione per il carcinoma basale e squamoso e carcinomi in situ). 14. Storia di chetoacidosi diabetica. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in glycosylated haemoglobin (Hba1c) |
Variazione dell’emoglobina glicosilata (HbA1c) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 26 |
Dal valore basale dopo 26 settimane di trattamento |
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E.5.2 | Secondary end point(s) |
1. Change in HbA1c
2. Change in body weight (kg)
3. Change in fasting plasma glucose
4. Achieved HbA1c < 7.0 % (53 mmol/mol) American Diabetes Association target (yes/no)
5. Number of treatment-emergent adverse events
6. Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes
; 1. Valore di HbA1c 2. Peso corporeo (kg) 3. Valore di FPG 4. Raggiungimento di HbA1c < 7.0% target dell'American Diabetes Association 5. Numero di eventi avversi correlati al trattamento 6. Numero di eventi avversi acuti correlati al trattamento oppure episodi ipoglicemici sintomatici confermati da valori registrati con glucometro |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From baseline to week 52
2. + 3. From baseline to week 26 and week 52
4. After week 26 and week 52
5. + 6. During exposure to trial product, assessed up to approximately 57 weeks
; 1. Dal baseline alla settimana 52 2-3. Dal baseline alle settimane 26 e 52 4. Dopo la settimana 26 e 52 5-6. Durante l'esposizione al prodotto sperimentale, valutato approssimativamente alla settimane 57 |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerabilty |
Tollerabilità |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Brazil |
Russian Federation |
Serbia |
Thailand |
United States |
European Union |
Argentina |
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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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LVLS |
Ultima Visita dell'ultimo paziente (Last Patient Last Visit) |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 3 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 3 |