E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Dijabetes Mellitus tip 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Dijabetes tipa 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 | 20.1 |
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 semaglutide once-weekly on glycaemic control versus insulin aspart three
times daily, both as add on to metformin and optimised insulin glargine (U100) in subjects with
type 2 diabetes. |
Usporediti učinak na glikemijsku kontrolu semaglutida primijenjenog jedanput tjedno u odnosu na učinak aspart inzulina primijenjenog tri puta dnevno, oba kao dodatak metforminu i optimalnoj dozi glargin inzulina (U100), u bolesnika sa šećernom bolesti tipa 2 |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate that semaglutide once-weekly lowers the risk of severe hypoglycaemic episodes
compared to insulin aspart three times daily, both as add on to metformin and optimised insulin
glargine (U100) in subjects with type 2 diabetes.
2. To compare the effect of semaglutide once-weekly versus insulin aspart three times daily, both as
add on to metformin and optimised insulin glargine (U100) in subjects with type 2 diabetes with
regards to:
-body weight
-lipids
-blood pressure
-health-related quality of life
-safety |
Pokazati da semaglutid primijenjen jedanput tjedno smanjuje rizik od teških hipoglikemijskih epizoda u usporedbi s aspart inzulinom primijenjenim tri puta dnevno, oba kao dodatak metforminu i optimalnoj dozi glargin inzulina (U100), u bolesnika sa šećernom bolesti tipa 2.
Usporediti učinak semaglutida primijenjenog jedanput tjedno u odnosu na učinak aspart inzulina primijenjenog tri puta dnevno, oba kao dodatak metforminu i optimalnoj dozi glargin inzulina (U100), u bolesnika sa šećernom bolesti tipa 2 vezano uz:
• tjelesnu težinu
• lipide
• krvni tlak
• kvalitetu života povezanu sa zdravljem
• sigurnost |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age greater than or equal to 18 years at the time of signing informed consent
- Diagnosed with type 2 diabetes greater than or equal to 180 days prior to the day of screening
- Treated with basal insulin once daily or twice daily for greater than or equal to 90 days prior to the day of screening
- Stable daily dose for 90 days prior to the day of screening of the following anti-diabetic drugs or combination regimens: Any metformin formulations (greater than or equal to 1500 mg to less than or equal to 3000 mg or maximum tolerated or effective dose documented in subject's medical record), alone or in combination (including fixed-dose drug combination) with up to one additional of the following oral antidiabetic drugs: sulfonylureas, meglitinides, dipeptidyl peptidase-4 inhibitors or alpha-glucosidase inhibitors
- Haemoglobin A1c (HbA1c) of greater than 7.5% to less than or equal to 10.0% (greater than 58 mmol/mol to less than or equal to 86 mmol/mol) |
- Muškarci ili žene, u dobi ≥ 18 godina u vrijeme potpisivanja Informiranog pristanka
- Postavljena dijagnoza šećerne bolesti tipa 2 ≥ 180 dana prije probira
- Liječenje bazalnim inzulinom jedanput ili dvaput dnevno ≥ 90 dana prije probira
- 90 dana prije probira potrebna je stabilna dnevna doza sljedećih antidijabetika ili kombinacije režima liječenja:
Bilo koja formulacija metformina (≥ 1500 mg do ≤ 3000 mg ili najveća podnošljiva ili učinkovita doza zabilježena u medicinskom kartonu bolesnika), primijenjena pojedinačno ili u kombinaciji (uključujući kombinaciju lijekova fiksne doze) s najviše jednim od sljedećih antidijabetskih lijekova: derivati sulfonilureje, meglitinidi, inhibitori dipeptidil peptidaze 4 (DPP-4 inhibitori) ili inhibitori alfa-glukozidaze.
- HbA1c > 7.5% do ≤ 10.0% (>58 mmol/mol do ≤ 86 mmol/mol).
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E.4 | Principal exclusion criteria |
- History or presence of pancreatitis (acute or chronic)
- Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening
- Subjects presently classified as being in New York Heart Association Class IV
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term bolus insulin treatment for a maximum of 14 days prior to the day of screening is allowed
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to run-in |
- Povijest ili prisutnost pankreatitisa (akutnog ili kroničnog)
- Bilo što od sljedećeg: infarkt miokarda, moždani udar, hospitalizacija zbog nestabilne angine ili prolaznog ishemijskog napada u proteklih 180 dana prije dana probira
- Pacijenti koji su klasificirani u New York Heart Association (NYHA) klasa IV
- Planirana revaskularizacija koronarnih, karotidnih ili perifernih arterija, poznata na dan probira
- Liječenje bilo kojim lijekom za indikaciju dijabetesa ili pretilosti osim navedenih u uključnim kriterijima u razdoblju od 90 dana prije pronira. Međutim, dopušteno je kratkotrajno liječenje inzulinommaksimalno do 14 dana prije probira
- Nekontrolirana i potencijalno nestabilna dijabetička retinopatija ili makulopatija. Potvrđena pregledom dilatiranih pupila fundusa, od strane oftalmologa ili jednako kvalificiranog davatelja zdravstvene skrbi (npr optometra), u proteklih 90 dana prije početka perioda prilagođavanja doze ispitivanog lijeka
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c (%-point) |
Promjene vrijednosti HbA1c (%) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 52 |
Od početka do 52. tjedna |
|
E.5.2 | Secondary end point(s) |
1. Time to first event adjudication committee confirmed severe hypoglycaemic episode (American Diabetes Association)
2. Time to first event adjudication committee confirmed severe hypoglycaemic episode (American Diabetes Association) requiring hospitalisation, documented medical help, or is life threatening
3. Change in body weight (kg) |
1. Vrijeme do pojave prvog događaja teške hipoglikemijske epizode (prema American Diabetes Association)
2. Vrijeme do pojave prvog događaja teške hipoglikemijske epizode koja zahtjeva hospitalizaciju, dokumentiranu medicinsku pomoć, ili je po život opasna (prema American Diabetes Association)
3. Promjena u tjelesnoj težini (prema American Diabetes Association)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-2. From randomisation up to week 52
3. From baseline to week 52 |
1-2. Od randomizacije do 52. tjedna
3. Od početka ispitivanja do 52. tjedna |
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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 | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 168 |
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 |
Bosnia and Herzegovina |
European Union |
India |
Macedonia, the former Yugoslav Republic of |
Serbia |
South Africa |
Turkey |
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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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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 | 1 |
E.8.9.1 | In the Member State concerned days | 12 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 12 |