E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Diabetes Mellitus, Tip 2 |
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Dijabetes 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 | 19.0 |
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 compare the effect of once-daily dosing of 14 mg oral semaglutide versus 1.8 mg liraglutide subcutaneous and versus placebo, all in combination with metformin with or without a SGLT-2 inhibitor, on glycaemic control in subjects with type 2 diabetes mellitus (T2DM). |
Usporedba učinka doze od 14 mg oralnog semaglutida jednom dnevno u odnosu na 1,8 mg liraglutida subkutano te u odnosu na placebo, svi u kombinaciji s metforminom s ili bez inhibitora SGLT-2, na kontrolu glikemije u ispitanika sa šećernom bolešću tipa 2. |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the effect of once-daily dosing of 14 mg oral semaglutide versus 1.8 mg liraglutide subcutaneous and versus placebo, all in combination with metformin with or without a SGLT-2 inhibitor, on body weight in subjects with T2DM.
2. To compare the safety and tolerability of once-daily dosing of 14 mg oral semaglutide versus 1.8 mg liraglutide subcutaneous and versus placebo, all in combination with metformin with or without a SGLT-2 inhibitor, in subjects with T2DM.
|
1. Usporedba učinka doze od 14 mg oralnog semaglutida jednom dnevno u odnosu na 1,8 mg liraglutida subkutano te u odnosu na placebo, svi u
kombinaciji s metforminom s ili bez inhibitora SGLT-2, na tjelesnu težinu u ispitanika sa šećernom bolešću tipa 2.
2. Usporedba sigurnosti i podnošljivosti doze od 14 mg oralnog semaglutida jednom dnevno u odnosu na 1,8 mg liraglutida subkutano te u odnosu na placebo, svi u kombinaciji s metforminom s ili bez inhibitora SGLT-2, u ispitanika sa šećernom bolešću tipa 2. |
|
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. For Japan only: Male or female, age ≥ 20 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 7.0–9.5 % (53–80.3 mmol/mol) (both inclusive).
5. Stable daily dose of metformin (≥1500 mg or maximum tolerated dose as documented in the subject medical record) alone or in combination with a stable daily dose of a SGLT-2 inhibitor for at least 90 days prior to day of screening (fixed-dose combinations are allowed).
|
1. Informirani pristanak potpisan prije bilo koje aktivnosti vezane uz kliničko ispitivanje. Aktivnosti vezane uz ispitivanje su bilo koji postupci provedeni kao dio ispitivanja, uključujući aktivnosti utvrđivanja prikladnosti za ispitivanje.
2. Muški ili ženski ispitanik/ca ≥ 18 godina u vrijeme potpisivanja informiranog pristanka.
3. Šećerna bolest tipa 2 dijagnosticirana ≥ 90 dana prije probira.
4. HbA1c 7,0 – 9,5% (53 – 80,3 mmol/mol) (obje vrijednosti uključive).
5. Ispitanici na stabilnoj dnevnoj dozi metformina (≥ 1500 mg ili najviša podnošljiva doza dokumentirana u ispitanikovim medicinskim zapisima) sama ili u kombinaciji sa stabilnom dnevnom dozom inhibitora SGLT-2 najmanje 90 dana prije probira (kombinacije s fiksnim dozama su dozvoljene). |
|
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 (MEN 2) or Medullary Thyroid Carcinoma (MTC).
4. History of pancreatitis (acute or chronic).
5. History of major surgical procedures involving the stomach and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery).
6. Any of the following: myocardial infarction (MI), 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 (NYHA) Class IV.
8. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
9. Subjects with ALT > 2.5 × upper normal limit (UNL).
10. Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) < 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.
|
1. Žena koja je trudna, doji, planira zatrudnjeti ili je u reproduktivnoj dobi, a ne koristi odgovarajuću kontraceptivnu metodu (hormonski kontraceptivi, sterilizacija, intrauterini uložak, metode barijere – kondomi ili dijafragma u kombinaciji sa spermicidnim sredstvima /krema, pjene, gelovi/ i, ako je primjenjivo, suzdržavanje od odnosa).
2. Bilo koje stanje koje po mišljenju ispitivača može ugroziti sigurnost ispitanika ili pridržavanje plana ispitivanja.
3. Obiteljska ili osobna anamneza multiple endokrine neoplazije tipa 2 ili medularnog karcinoma štitnjače.
4. Anamneza pankreatitisa (akutni ili kronični).
5. Anamneza velikih operacijskih postupaka koji zahvaćaju želudac s potencijalnim učinkom na apsorpciju ispitivanog lijeka (npr. parcijalna ili totalna gastrektomija, sleeve gastrektomija, ugradnja želučane premosnice).
6. Bilo koje od slijedećeg: infarkt miokarda, moždani udar ili hospitalizacija zbog nestabilne angine ili tranzitorne ishemične atake unutar 180 dana prije probira.
7. Ispitanici koji su trenutno svrstani u klasu IV prema New York Heart Association.
8. Planirana koronarna, karotidna, ili periferna arterijska revaskularizacija poznata na dan probira.
9. Ispitanici s ALT > 2,5 x gornje granične vrijednosti
10. Oštećenje bubrega definirano s EGFR < 60 mL/min/1,73 m2 prema CKD-EPI jednadžbi .
11. Liječenje bilo kojim lijekom indiciranim za dijabetes ili pretilost osim nevedenih u uključnim kriterijima u razdoblju od 90 dana prije probira. Iznimka je kratkotrajno liječenje akutnih stanja inzulinom u trajanju ukupno ≤ 14 dana.
12. Proliferativna retinopatija ili makulopatija koja zahtijeva akutno liječenje. Potvrđeno fotografijom fundusa ili dilatiranom fundoskopijom napravljenom u razdoblju od 90 dana prije randomizacije.
13. Anamneza ili prisutnost malignih neoplazija unutar 5 godina (osim karcinoma bazalnih i skvamoznih stanica i karcinoma in situ).
14. Anamneza dijabetičke ketoacidoze. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c |
Promjena u HbA1c |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 26 |
Od početnih vrijednosti do 26. tjedna |
|
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. Promjena u HbA1c
2. Promjena u tjelesnoj težini (kg)
3. Promjena u vrijednosti glukoze u plazmi natašte
4. Postignut (da/ne) HbA1c < 7,0 % (53 mmol/mol), što je cilj Američkog društva za kliničku endokrinologiju
5. Broj neželjenih događaja kao posljedica liječenja
6. Broj teških ili potvrđenih vrijednostima glukoze u krvi simptomatskih hipoglikemijskih epizoda kao posljedica liječenja |
|
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. Od početnih vrijednosti do 52. tjedna
2. + 3. Od početnih vrijednosti do tjedna 26 i 52
4. Nakon 26 i 52 tjedna liječenja
5. + 6. Tijekom izloženosti ispitivanom lijeku, procijenjuje se oko 57 tjedana |
|
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 |
Podnošljivost |
|
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
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 |
Japan |
South Africa |
Ukraine |
United Arab Emirates |
United States |
|
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
|
|
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 | 24 |
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 | 24 |