E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Šećerna bolest tipa 2 |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Šećerna bolest 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 | 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 confirm superiority of once weekly IcoSema compared with once weekly insulin icodec, both treatment arms with or without OADs, in terms of glycaemic control measured by change in HbA1c from baseline after 52 weeks in participants with T2D inadequately controlled with daily basal insulin. |
Cilj ovog ispitivanja je potvrditi superiornost IcoSeme u odnosu na icodec inzulin, primijenjenih jedanput tjedno s ili bez oralnih antidijabetika na kontrolu glikemije u ispitanika sa šećernom bolešću tipa 2 koji su neodgovarajuće kontrolirani na terapiji dnevnim bazalnim inzulinom. |
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E.2.2 | Secondary objectives of the trial |
- To confirm superiority of once weekly IcoSema compared to once weekly insulin icodec, both treatment arms with or without OADs, in participants with T2D inadequately controlled with daily basal insulin in terms of: • Change in body weight from baseline after 52 weeks • Number of clinically significant hypoglycaemic (level 2) or severe hypoglycaemic (level 3) episodes during 52 weeks and the 5 week follow up period - To compare parameters of glycaemic control and safety of once weekly IcoSema with once weekly insulin icodec, both treatment arms with or without OADs, in participants with T2D inadequately controlled with daily basal insulin. |
Potvrda superiornosti IcoSeme u odnosu na icodec inzulin, primijenjenih jedanput tjedno s ili bez oralnih antidijabetika u ispitanika sa šećernom bolešću tipa 2 koji su neodgovarajuće kontrolirani na terapiji dnevnim bazalnim inzulinom u vidu: • promjene u tjelesnoj težini od početka ispitivanja do 52. tjedna • broja kliničkih značajnih hipoglikemijskih epizoda (razina 2) ili teških hipoglikemisjskih epizoda (razina 3) tijekom 52 tjedna i 5 tjedana nakon završetka ispitivanja -uporedba kontrole glikemije i sigurnosti primjene IcoSeme u odnosu na icodec inzulin, primijenjenih jedanput tjedno s ili bez oralnih antidijabetika u ispitanika sa šećernom bolešću tipa 2 koji su neodgovarajuće kontrolirani na terapiji dnevnim bazalnim inzulinom
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female and age above or equal to 18 years at the time of signing informed consent. - Diagnosed with type 2 diabetes mellitus 180 days or more before screening. - Glycated haemoglobin (HbA1c) of 7.0-10.0% (53.0-85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening. - Treated with once daily or twice daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20-80 units/day 90 days or more before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti diabetic drugs with stable doses above or equal to 90 days before screening: • Metformin • Sulfonylureas * • Meglitinides (glinides) * • DPP 4 inhibitors * • Sodium glucose co transporter 2 inhibitors • Alpha glucosidase inhibitors • Thiazolidinediones • Marketed oral combination products only including the products listed above. - Body mass index (BMI) less than or equal to 40.0 kg/m^2.
* Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation. |
- Muškarci i žene u dobi od ≥ 18 godina u vrijeme potpisivanja Informiranog pristanka - Dijagnoza šećerne bolesti tipa 2 ≥ 180 dana prije probira - Vrijednost HbA1c od 7,0-11,0% na dan probira prema nalazu centralnog laboratorija - Ispitanici na terapiji bazalnim inzulinom jedanput ili dvaput dnevno (neutralni protamin hagedorn inzulin, degludek inzulin, detemir inzulin, glargin inzulin 100 jedinica/mL ili 300 jedinica/mL) 20-80 jedinica dnevno ≥ 90 dana prije probira. Međutim, dozvoljeno je kratkotrajno liječenje bolus inzulinom do maksimalno 14 dana prije probira, kao i liječenje gestacijskog dijabetesa inzulinom. Liječenje šećerne bolesti tipa 2 stabilnom dnevnom dozom ≥ 90 dana prije probira bilo kojih od sljedećih antidijabetičkih lijekova: • metformin • sulfonilureje* • meglitinidi (glinidi)* • inhibitori DPP-4* • inhibitori SGLT2 • inhibitori alfa-glukozidaze • tiazolidindioni • kombinacije oralnih lijekova (isključivo gore navedenih) - Indeks tjelesne težine (BMI) ≤ 40,0 kg/m2 * liječenje sulfonilurejama, meglitinidima (glinidi) i inhibitorima DPP-4 mora se prekinuti prije randomizacije
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E.4 | Principal exclusion criteria |
- Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method. - Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid, hormones, or systemic corticosteroids). - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. - Any episodes (as declared by the participant or in the medical records) of diabetic ketoacidosis within 90 days before screening. - Presence or history of pancreatitis (acute or chronic) within 180 days before screening. - Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening. - Chronic heart failure classified as being in New York Heart Association Class IV at screening. - Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator. - Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil dilation is a requirement unless using a digital fundus photography camera specified for non dilated examination. |
-Žena koja je trudna, doji,namjerava zatrudnjeti ili je u reproduktivnoj dobi i ne koristi visoko učinkovitu metodu kontracepcije -Očekivani početak ili promjena istodobnog uzimanja lijekova (dulje od 14 uzastopnih dana) za koje se zna da utječu na težinu ili metabolizam glukoze (npr. liječenje orlistatom, hormonima štitnjače ili sistemskim kortikosteroidima) -Liječenje bilo kojim lijekom indiciranim za dijabetes ili pretilost osim navedenog u kriterijima za uključivanje unutar 90 dana prije probira -Bilo kakva epizoda dijabetičke ketoacidoze (bilo rečena od strane ispitanike ili navedena u medicinskoj dokumentaciji) unutar 90 dana prije probira -Postojanje ili anamneza pankreatitisa (akutnog ili kroničnog) unutar 180 dana prije probira -Bilo što od sljedećeg: infarkt miokarda, moždani udar, hospitalizacija zbog nestabilne angine pektoris ili prolaznog ishemijskog napada unutar 180 dana prije probira -Kronično zatajenje srca klasificirano kao NYHA (New York Heart Association) klasa IV na probiru -Ponavljajuće teške hipoglikemijske epizode u posljednjih godinu dana (12 mjeseci) prema procjeni glavnog ispitivača -Nekontrolirana i potencijalno nestabilna dijabetička retinopatija ili makulopatija. Potvrđeno pregledom fundusa obavljenim u posljednjih 90 dana prije probira ili u razdoblju između probira i randomizacije. Farmakološko širenje zjenica je uvjet osim ako se ne koristi digitalna kamera za fotografiranje fundusa koja je određena za nedilatirani pregled
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in glycated haemoglobin (HbA1c) |
Promjena u vrijednosti HbA1c |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline week 0 (V2) to week 52 (V54) |
Od početka ispitivanja tjedan 0 (V2) do 52. tjedna (V54) |
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E.5.2 | Secondary end point(s) |
1. Change in body weight 2. Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) 3. Time in range 3.9 10.0 mmol/L (70 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 4. Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 5. Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 6. Change in fasting plasma glucose (FPG) 7. Weekly basal insulin dose 8. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) 9. Number of severe hypoglycaemic episodes (level 3) |
1. Promjena u tjelesnoj težini 2. Broj klinički značajnih hipoglikemijskih epizoda (vrijednost šećera u krvi mjererena glukometrom < 3.0 mmol/L) ili teške hipoglikemijske epizode 3. Vrijeme u kojem je vrijednost šećera u krvi bila unutar ciljanog raspona od 3.9 do 10.0 mmol/L izmjerenom koristeći sustav za kontinuirano mjerenje šećera u krvi (CGM), Dexcom G6 4. Vrijeme u kojem je vrijednost šećera u krvi bila < 3.0 mmol/L izmjerenom koristeći sustav za kontinuirano mjerenje šećera u krvi (CGM), Dexcom G6 5. Vrijeme u kojem je vrijednost šećera u krvi bila iznad 10.0 mmol/L zmjerenom koristeći sustav za kontinuirano mjerenje šećera u krvi (CGM), Dexcom G6 6. Promjena vrijednosti šećera u krvi mjerena natašte (FPG) 7. Tjedna doza balnog inzulina 8. Broj klinički značajnih hipoglikemijskih epizoda (vrijednost šećera u krvi < 3 mmol/L) izmjereno glukometrom 9. Broj teških hipoglikemijskih epizoda
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From baseline week 0 (V2) to week 52 (V54) 2. From baseline week 0 (V2) to week 57 (V56) 3-5. From week 48 (V50) to week 52 (V54) 6. From baseline week 0 (V2) to week 52 (V54) 7. From week 50 (V52) to week 52 (V54) 8-9. From baseline week 0 (V2) to week 57 (V56) |
1. Od početka ispitivanja tjedan 0 (V2) do 52. tjedna (V54) 2. Od početka ispitivanja tjedan 0 (V2) do 57. tjedna (V56) 3.-5. Od 48. tjedna (V50) do 52. tjedna (V54) 6. Od početka ispitivanja tjedan 0 (V“) do 52. tjedna (V54) 7. Od 50- tjedna (V52) do 52. tjedna (V54) 8.-9. Od početka ispitivanja tjedan 0 (V2) do 57. tjedna (V56)
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Australia |
China |
India |
Japan |
Korea, Republic of |
Mexico |
South Africa |
Taiwan |
United States |
European Union |
Norway |
Russian Federation |
Serbia |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 22 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 22 |