E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 1 |
Dijabetes tipa 1 |
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E.1.1.1 | Medical condition in easily understood language |
Type 1 diabetes |
Šećerna bolest tipa 1 |
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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 | 10045228 |
E.1.2 | Term | Type I 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 |
1. To compare the effect on glycaemic control of insulin degludec once daily plus insulin aspart 2-4
times daily with meals and insulin detemir once daily or twice daily plus insulin aspart 2-4 times
daily with meals in a population of pregnant women with type 1 diabetes mellitus. |
1. Usporedba učinka na kontrolu glikemije degludek inzulina primijenjenog jednom dnevno i detemir inzulina primijenjenog jednom il dva puta dnevno, oba uz aspart inzulin primijenjen 2-4 puta dnevno uz obroke u trudnica sa šećernom bolešću tipa 1. |
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E.2.2 | Secondary objectives of the trial |
1. To compare the effect on maternal safety of insulin degludec once daily plus insulin aspart 2-4
times daily with meals and insulin detemir once daily or twice daily plus insulin aspart 2-4 times
daily with meals in a population of pregnant women with type 1 diabetes mellitus.
2. To compare the effect on pregnancy outcome of insulin degludec once daily plus insulin aspart 2-4
times daily with meals and insulin detemir once daily or twice daily plus insulin aspart 2-4 times
daily with meals in a population of pregnant women with type 1 diabetes mellitus. |
1. Usporedba učinka na sigurnost majke degludek inzulina primijenjenog jednom dnevno i detemir inzulina primijenjenog jednom ili dva puta dnevno, oba uz aspart inzulin primijenjen 2-4 puta dnevno uz obroke u trudnica sa šećernom bolešću tipa 1.
2. Usporedba učinka na ishod trudnoće degludek inzulina primijenjenog jednom dnevno i detemir inzulina primijenjenog jednom ili dva puta dnevno, oba uz aspart inzulin primijenjen 2-4 puta dnevno uz obroke u trudnica sa šećernom bolešću tipa 1.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Female, age at least 18 years at the time of signing informed consent
- Diagnosed with type 1 diabetes mellitus for at least 1 year prior to the day of screening
- Treated with multiple daily subcutaneous insulin injections or continuous subcutaneous insulin infusion (CSII) or inhaled insulin for at least 90 days prior to the day of screening
- The subject is planning to become pregnant within 12 months from randomisation and willing to undertake pre-pregnancy counselling or the subject is pregnant with an intrauterine singleton living foetus (gestational week 8 to 13 (+6 days)) without any observed anomalies at randomisation, confirmed by an ultrasound scan
- HbA1c at screening below or equal to 8.0% (64 mmol/mol) by central laboratory |
- Žene u dobi ≥ 18 godina u vrijeme potpisivanja Informiranog pristanka
- Dijagnosticirana šećerna bolest tipa 1 najmanje godinu dana prije probira
- Liječenje sa više dnevnih supkutanih injekcija inzulina ili kontinuiranom supkutanom infuzijom inzulina („inzulinske pumpe“) ili inhalacijskim inzulinom najmanje 90 dana prije probira
- Ispitanica planira ostati trudna unutar 12 mjeseci od randomizacije i voljna je proći kroz prekoncepcijsko savjetovanje ili je trudna 8-13 (+6) tjedana sa urednom jednoplodnom trudnoćom bez uočenih anomalija potvrđenom nalazom ultrazvuka na randomizaciji
- HbA1c na probiru ≤ 8.0% izmjereno u centralnom laboratoriju
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E.4 | Principal exclusion criteria |
- 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
- Pregnant and having proteinuria as evaluated by urine protein-to-creatinine ratio above or equal to 300 mg/g in urine sample measured at screening
- Subject being treated or became pregnant with assistance of in vitro fertilisation or other medical infertility treatment
- Receipt of any concomitant medication contraindicated in pregnancy according to local label within 28 days before screening and between screening and randomisation for non-pregnant subjects and 28 days before conception and between conception and randomisation for pregnant subjects
- Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or pharmacologically dilated fundoscopy performed within the past 90 days prior to randomisation for non-pregnant subjects or within 28 days prior to randomisation for pregnant subjects
- History of severe hyperemesis gravidarum (requiring hospitalisation) |
- Liječenje šećerne bolesti ili pretilosti bilo kojim lijekovima koji nisu navedeni u kriterijima za uključivanje pacijenata unutar 90 dana prije probira
- Trudnoća uz prisutnu proteinuriju potvrđenu prisutnošću proteina i kreatinina u kolićini ≥ 300 mg/g u uzorku urina, analizirano na dan probira
- Ispitanica koja zatrudni pomoću in vitro oplodnje ili se liječi medicinskim tretmanima od neplodnosti
- Istovremeno korištenje bilo kojeg lijeka kontraindiciranog u trudnoći unutar 28 dana prije probira, 28 dana prije zaćeća te zmeđu zaćeća i randomizacije
- Proliferativna retinopatija ili makulopatija koja zahtijeva akutno liječenje. Potvrđena slikom fundusa ili farmakološki dilatiranom fundoskopijom obavljenom unutar 28 dana prije randomizacije.
- Medicinska povijest teške trudničke hiperemezije čije je liječenje zahtijevalo hospitalizaciju
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Last planned glycosylated haemoglobin (HbA1c) prior to delivery |
1. Posljednja vrijednost glikoziliranog hemoglobina (HbA1c)u uzorku krvi mjereno prije poroda |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. After gestational week 16 |
1. Nakon 16.-tog gestacijskog tjedna |
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E.5.2 | Secondary end point(s) |
Supportive maternal efficacy endpoints
1. HbA1c ≤ 6.0% (42 mmol/mol) from last planned HbA1c prior to delivery (yes/no)
2. Last planned average post-prandial glucose prior to delivery. Average of three main meals.
3. Last planned fasting plasma glucose prior to delivery
Supportive maternal safety endpoints
4. Number of hypoglycaemic episodes
5. Development of sight-threatening retinopathy defined as proliferative retinopathy or
maculopathy (yes/no)
6. Number of adverse events during the pregnancy period
7. Pre-eclampsia defined as new-onset hypertension (blood pressure ≥ 140 mmHg systolic or
≥ 90 mmHg diastolic, based on at least 2 measurements taken at least 4 hours apart)and simultaneous proteinuria (defined as ≥ 300 mg protein in a 24 hours urine sample, a protein-to-creatinine ratio of ≥ 300 mg/g in a urine sample or a urine dipstick protein of 1+) or presence of eclampsia, HELLP syndrome, or other severe organ involvement (yes/no)
Supportive pregnancy outcome endpoints
8. Birth weight (kg)
9. Pre-term delivery (delivery < 37 completed gestational weeks) (yes/no)
10. Presence of major abnormalities (classified according to EUROCAT) (yes/no)
11. Live born infants (yes/no)
12. Number of adverse events in the infant
13. Neonatal hypoglycaemic episodes defined as plasma glucose ≤ 1.7 mmol/L (31 mg/dL) during the first 24 hours after birth or ≤ 2.5 mmol/L (45 mg/dL) between 24 hours and 48 hours after birth (yes/no) |
Dodatni pokazatelji učinkovitosti ispitivanog lijeka kod majke:
1. HbA1c ≤ 6,0% od posljednjeg planiranog mjerenja HbA1c prije poroda (da / ne)
2. Posljednje planirano mjerenje prosječne vrijednosti glukoze u krvi nakon 3 glavna obroka (post-prandijalna vrijednost) prije poroda
3. Posljednje planirano mjerenje vrijednosti glukoze natašte prije poroda
Dodatni pokazatelji sigurnosti primjene ispitivanog lijeka kod majke:
4. Broj epizoda hipoglikemije
5. Razvoj retinopatije koja može oštetiti vid definirana kao proliferativna retinopatija ili makulopatija (da /ne)
6. Broj štetnih događaja tijekom trudnoće
7. Preeklapsija definirana kao novi 'napad' hipertenzije ( sistolički krvni tlak ≥ 140 mmHg ili dijastolički ≥ 90 mmHg, temeljeno na posljednja 2 mjerenja učinjena u razmaku od najmanje 4 sata) i istodobno prisutne proteinurije (definirane kao prisutnost ≥ 300 mg proteina u uzorku 24-satnog urina, te razina proteina i kreatinina ≥ 300 mg/g u uzorku urina ili protein 1+ na trakici za analizu urina) ili prisutnost eklapsije, HELLP sindoma ili druga teška oštećenja organa (da / ne)
Dodatni pokazatelji ishoda trudnoće
8. Porođajna težina (kg)
9. Prijevremeni porođaj (<37 gestacijskog tjedna) (da / ne)
10. Prisutnost teških anomalija (klasifikacija prema EUROCAT-u) (da / ne)
11. Živorođena djeca (da / ne)
12. Broj štetnih događaja kod novorođenčadi
13. Neonatalne epizode hipoglikemije definirane kao glukoza u plazmi ≤ 1,7 mmol / L tijekom prva 24 sata nakon rođenja ili ≤ 2,5 mmol / L u periodu između 24 sata i 48 sati nakon rođenja (da / ne)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.-3. After gestational week 16
4. During the pregnancy period (from first day of pregnancy (date of conception) or randomisation (whichever comes last) to delivery)
5. From treatment baseline as well as from pregnancy baseline to the end of treatment visit
6. From first day of pregnancy (date of conception) or randomisation (whichever comes last) to delivery)
7. occurring from gestational week 20 to delivery
8. - 11. At birth
12. From delivery to final follow-up
13. During the first 24 hours after birth or between 24 hours and 48 hours after birth |
1.-3. Nakon 16.-tog gestacijskog tjedna
4. Tijekom trudnoće (od prvog dana trudnoće (datum začeća) ili randomizacije (ovisno o tome koje je posljednje) do poroda)
5. Od početka liječenja kao i od početka trudnoće do posljednjeg posjeta
6. Od prvog dana trudnoće (dan začeća) ili randomizacije (ovisno o tome koje je posljednje) do poroda)
7. Pojavnost od 20.-tog gestacijskog tjedna do poroda
8.-11. Pri rođenju
12. Od poroda do posljednjeg kontrolnog pregleda
13. Tijekom prvih 24 satza nakon rođenja ili u periodu od 24 do 48 sati nakon rođenja
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 |
Argentina |
Australia |
Brazil |
Canada |
European Union |
Israel |
Russian Federation |
Serbia |
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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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 6 |