E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
diabete mellito, tipo 2. |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
diabete mellito, 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 | 16.0 |
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 demonstrate superiority of once-weekly dosing of two dose levels of semaglutide versus placebo on glycaemic control after 30 weeks of treatment in drug-naïve subjects with type 2 diabetes |
Dimostrare la superiorità di due diversi dosaggi di semaglutide somministrata una volta la settimana rispetto al placebo sul controllo glicemico dopo 30 settimane di trattamento in pazienti con diabete di tipo 2 mai trattati. |
|
E.2.2 | Secondary objectives of the trial |
To compare the effects of once-weekly dosing of two dose levels of semaglutide versus placebo after 30 weeks of treatment on:
- Inducing and maintaining weight loss
- Other parameters of efficacy, safety and tolerability |
Confrontare gli effetti della somministrazione una volta a settimana dei due diversi dosaggi di semaglutide rispetto al placebo dopo 30 settimane di trattamento sui seguenti parametri:
- Induzione e mantenimento della perdita di peso corporeo
- Altri parametri di efficacia, sicurezza e tollerabilità |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, age equal to or above 18 years at the time of signing informed consent
2. For Japan only: Male or female, age equal to or above 20 years at the time of signing informed consent
3. Subjects diagnosed with type 2 diabetes and treated with diet and exercise for at least 30 days before screening
4. HbA1c 7.0 – 10.0 % (53 - 86 mmol/mol) (both inclusive) |
1. Uomini e donne di età ≥ 18 anni al momento della firma del consenso informato.
2. Solo per il Giappone: Uomini e donne di età ≥ 20 anni al momento della firma del consenso
informato.
3. Pazienti con diagnosi di diabete di tipo 2 in trattamento con dieta ed esercizio fisico per
almeno 30 giorni prima dello screening.
4. HbA1c 7,0 – 10,0 % (53 - 86 mmol/mol) (entrambi compresi). |
|
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 adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice) throughout the trial including the 5 week follow-up period. United Kingdom: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilisation (where partner is sole partner of subject), or true abstinence (when in line with preferred and usual lifestyle)
2. Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject’s safety or compliance with the protocol
3. Treatment with any glucose lowering agent(s) in a period of 90 days prior to screening. An exception is short-term treatment (equal to or less than 7 days in total) with insulin in connection with inter-current illness
4. History of chronic or idiopathic acute pancreatitis
5. Screening calcitonin value equal to or above 50 ng/L (pg/mL)
6. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2)
7. Impaired renal function defined as eGFR below 30 mL/min/1.73 m^2 per modification of diet in renal disease (MDRD) formula (4 variable version)
8. Acute coronary or cerebrovascular event within 90 days before randomisation
9. Heart failure, New York Heart Association class IV |
1. Donne in età fertile in stato di gravidanza, in allattamento al seno, che stiano pianificando
una gravidanza o che non utilizzino adeguati metodi contraccettivi (metodi di contraccezione adeguati secondo quanto previsto dalle leggi vigenti o dalle procedure locali) per tutta la durata dello studio, comprese le 5 settimane del periodo di controllo
(follow-up).
2. Malattie croniche o gravi patologie che, secondo il medico sperimentatore, potrebbero mettere a rischio la sicurezza del paziente, l’aderenza (compliance) al protocollo.
3.Trattamento con agenti ipoglicemizzanti nei 90 giorni precedenti lo screening. Eccezione fatta per il trattamento a breve termine (≤ 7 giorni ) con insulina per il trattamento di una malattia intercorrente.
4. Storia di pancreatite cronica o pancreatite acuta idiopatica.
5. Valori di calcitonina allo screening ≥ 50 ng/L (pg/mL).
6. Storia personale o familiare di carcinoma midollare della tiroide (MTC) o neoplasia endocrina multipla di tipo 2 (MEN 2).
7. Funzione renale ridotta definita come stima della filtrazione glomerulare (eGFR) < 30
mL/min/1.73 m2, secondo la formula MDRD (versione a 4 variabili).
8. Eventi acuti coronarici o cerebrovascolari verificatisi nei 90 giorni precedenti la randomizzazione.
9. Insufficienza cardiaca, classe IV NYHA (New York Heart Association).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c |
Variazione del valore di HbA1c |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 30 |
rispetto al valore basale dopo 30 settimane di trattamento |
|
E.5.2 | Secondary end point(s) |
Change in
1. Body weight
2. Fasting plasma glucose
3. Systolic and diastolic blood pressure
Subjects who achieve (yes/no):
4. HbA1c below 7.0% (53 mmol/mol) American Diabetes Association target
5. HbA1c equal to or below 6.5% (48 mmol/mol) American Association of Clinical Endocrinologists target |
Variazione dei seguenti valori basali:
1. peso
2. glicemia a digiuno
3. Pressione arteriosa sistolica e diastolica
Pazienti che conseguono o meno i seguenti valori:
4. HbA1c <7,0% (53 mmol/mol), target stabilito dalla American Diabetes Association
5. HbA1c ≤6,5% (48 mmol/mol), target stabilito dalla American Association of Clinical
Endocrinologists
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. + 2. + 3.: From baseline to week 30
4. + 5.: After 30 weeks' treatment |
1. + 2. + 3.: fino alla trentesima settimana a partire dalla baseline
4. + 5.: Dopo 30 settimane di trattamento |
|
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 |
Tolerability |
Tollerabilità |
|
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 | 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 | 30 |
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 |
Canada |
Japan |
Mexico |
Russian Federation |
South Africa |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 14 |