E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Dijabetes tipa 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Šećerna bolest tipa 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 | 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 |
|
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. |
Pokazati da primjena oralnog semaglutida smanjuje rizik od MACE u usporedbi s placebom, oba dodana standardnom liječenju, u osoba sa šećernom bolešću tipa 2 i visokim rizikom za kardiovaskularne događaje |
|
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 |
Usporedba učinka oralnog semaglutida u usporedbi s placebom, oba dodana standardnom liječenju, u bolesnika sa šećernom bolešću tipa 2 i visokim rizikom za kardiovaskularne događaje vezano uz:
- kroničnu bubrežnu bolest
- kardiovaskularne događaje
- perifernu arterijsku bolest
- kontrolu glikemije i tjelesnu težinu
- sigurnost
|
|
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, computerized 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, computerized 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) below 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, computerized 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 below 60 mL/min/1.73 m^2 (Based on medical records using latest available and no more than 6 months old assessment). |
1. Muškarci ili žene u dobi ≥ 50 godina u vrijeme potpisivanja Informiranog pristanka
2. Dijagnoza šećerne bolesti tipa 2
3. HbA1c 6.5%-10% (na temelju laboratorijskih nalaza ne starijih od 30 dana)
4. Barem jedna od sljedećih dijagnoza:
a. koronarna srčana bolest definirana kao najmanje jedno od sljedećeg:
i. Preboljen infarkta miokarda
ii. Prethodni postupak koronarne revaskularizacije
iii. Stenoza koronarne arterije jednaka ili veća od 50% ustanovljena kateterizacija srca, kompjuteriziranom tomografijom koronarne angiografije
iv. Koronarna bolest srca s ishemijom potvrđena stresnim testom
s bilo kojim načinom prikazivanja
b) Cerebrovaskularna bolest definirana kao najmanje jedno od sljedećeg:
i. Preboljen moždani udar
ii. Prethodni postupak revaskularizacije karotidnih arterija
iii. Stenoza jednaka ili veća od 50% u karotidnoj arteriji potvrđena angiografijom, magnetskom rezonancijom, kompjutoriziranom tomografskom angiografijom ili Doppler ultrazvukom
c) Simptomatska bolest perifernih arterija (BPA) definirana kao najmanje jedna od sljedećeg:
i. Povremena klaudikacija s gležanjsko-brahijalnim indeksom (ABI) ispod
0.85 u mirovanju
ii. Povremena klaudikacija sa stenozom jednakom ili iznad 50% u
periferna arterija (osim karotide) potvrđena rendgenskom angiografijom,
magnetskom rezonancijskom angiografijom, kompjutoriziranom tomografskom angiografijom ili Doppler ultrazvukom
iii. Prethodna revaskularizacija perifernih arterija (isključujući karotidnu)
iv. Amputacija donjih ekstremiteta na ili iznad gležnja zbog ateroskleroze (isključujući npr. traumu ili osteomijelitis)
d) Kronična bubrežna bolest definirana kao:
i. eGFR ispod 60 ml / min / 1,73 m ^ 2 (na temelju povijesti bolesti ne starijih od od 6 mjeseci).
|
|
E.4 | Principal exclusion criteria |
1. Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
2. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
3. Heart failure presently classified as being in New York Heart Association Class IV
4. Treatment with any glucagon-like peptide-1 receptor agonist within 30 days before screening |
1.Bilo što od sljedećeg: infarkt miokarda, moždani udar, hospitalizacija zbog nestabilne angine pektoris ili prolazni ishemijski napad u posljednjih 60 dana prije dana probira
2. Planirana revaskularizacija koronarnih, karotidnih ili perifernih arterija
poznata na dan probira
3. Zatajenje srca klasificirano kao Klasa IV prema NYHA smjernicama
4. Liječenje s bilo kojim agonistom receptora peptida-1 sličnog glukagonu
30 dana prije probira
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to first occurrence of a major adverse
cardiovascular event (MACE), a composite endpoint consisting of:
- CV death
- non-fatal myocardial infarction
- non-fatal stroke |
Vrijeme do prve pojave MACEa, kompozitnog ishoda kojeg čine:
- smrt uzrokovana kardiovaskularnim događajem,
- infarkt miokarda bez smrtnog ishoda
- moždani udar bez smrtnog ishoda
|
|
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) |
Vrijeme od randomizacije (0.-ti tjedan) do kraja ispitivanja (61 mjeseci ili više) |
|
E.5.2 | Secondary end point(s) |
1. Time to first occurrence of a composite endpoint consisting of:
- cardiovascular death
- renal death
- onset of persistent equal to or above 50% reduction in eGFR (CKD-EPI) (Compared with baseline)
- onset of persistent eGFR (CKD-EPI) below 15 mL/min/1.73 m^2
- initiation of chronic renal replacement therapy (dialysis or kidney transplantation)
2. Time to occurrence of cardiovascular death
3. Time to first occurrence of major adverse limb events (MALE), a composite endpoint consisting of:
- acute limb ischemia hospitalisation
- chronic limb ischemia hospitalisation |
Sekundarni:
1.Vrijeme do prve pojave kompozitne mjere ishoda koja se sastoji od:
-kardiovaskularne smrti
-renalne smrti
-pojave stalnog smanjenja eGFR ≥ 50% u usporedbi s početnom vrijednosti
- stalne pojave eGFR ispod 15 mL/min/1.3 m2
-uvođenje kronične nadomjesne bubrežne terapije (dijaliza ili transplantacija bubrega)
2. Vrijeme do pojave smrti uzrokovane kardiovaskularnim događajem
3.Vrijeme do prve pojave velikog štetnog događaja udova (engl. major adverse limb events, MALE) (hospitalizacija zbog akutne ili kronične ishemije udova)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints:
From randomisation (week 0) to end-of-trial (up to 61 months or more) (trial is event driven) |
Sve sekundarne mjere ishoda:
Vrijeme od randomizacije (0.-ti tjedan) do kraja ispitivanja (61 mjeseci ili više)
|
|
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 | 8 |
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 | 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 |
Algeria |
Argentina |
Brazil |
Canada |
China |
Colombia |
European Union |
Hong Kong |
India |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Russian Federation |
Serbia |
South Africa |
Taiwan |
Thailand |
Turkey |
Ukraine |
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 | 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 |