E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
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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 the efficacy of SIBA + insulin aspart in controlling glycaemia with respect to change from baseline in HbA1c after 26 weeks of treatment. This is done by comparing the difference in change from baseline in HbA1c after 26 weeks of treatment between SIBA + insulin aspart and insulin detemir + insulin aspart to a non-inferiority limit of 0.4%, and if non-inferiority is confirmed, to a superiority limit of 0%. |
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E.2.2 | Secondary objectives of the trial |
To confirm superiority of SIBA + insulin aspart to insulin detemir + insulin aspart after 26 week of treatment in terms of: Nocturnal hypoglycaemic episodes (severe and minor) Hypoglycaemic episodes (severe and minor) Fasting plasma glucose (FPG) from central laboratory Within-subject variability in pre-breakfast self measured plasma glucose (SMPG) To compare efficacy and safety in terms of: Frequency of responders for HbA1c as specified in section 4.2 9-point profile (SMPG) 4-point profile (SMPG) for dose adjustments |
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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 defined as any procedure that would not have been performed during normal management of the subject) 2. Males or females, ≥ 18 years of age (≥ 20 years for Japan) 3. Type 1 diabetes mellitus (diagnosed clinically) ≥ 12 months 4. Current treatment with any basal/bolus insulin regimen for at least 12 months prior to Visit 1 5. HbA1c ≤ 10.0 % by central laboratory analysis 6. BMI ≤ 35.0 kg/m2 7. Ability and willingness to adhere to the protocol including performance of self measured plasma glucose (SMPG) profiles according to the protocol |
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E.4 | Principal exclusion criteria |
Use within the last 3 months prior to Visit 1 of any other antidiabetic glucose lowering drug than insulin 2. Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as systemic corticosteroids, beta-blockers, MAO inhibitors 3. Cardiovascular disease, within the last 6 months prior to visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA)2 class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty 4. Uncontrolled treated/untreated severe hypertension (systolic blood pressure ≥ 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure ≥ 100 mmHg) 5. Impaired liver function, defined as ALAT ≥ 2.5 times upper limit of normal (one re-test analysed at the central laboratory within a week from receipt of the result is permitted with the result of the last sample being conclusive) 6. Impaired renal function defined as serum-creatinine ≥ 180 μmol/L (≥ 2.0 mg/dl); one re-test within a week from receipt of the result is permitted. Last sample will be conclusive 7. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode during the last 12 months) or hypoglycaemic unawareness or hospitalisation for diabetic ketoacidosis during the previous 6 months 8. Proliferative retinopathy or maculopathy requiring treatment according to the Investigator 9. Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements (for UK: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, sterilisation, intrauterine device or intrauterine system, or consistent use of barrier methods) 10. Cancer and medical history of cancer (except basal cell skin cancer or squamous cell skin cancer) 11. Any clinically significant disease or disorder, except for conditions associated with type 1 diabetes, which in the Investigator s opinion could interfere with the results of the trial 12. Mental incapacity, psychiatric disorder, unwillingness or language barriers precluding adequate understanding or co-operation, including subjects not able to read or write 13. Previous participation in this trial. Participation is defined as randomised. Re-screening of screening failures is allowed only once within the limits of the recruitment period 14. Known or suspected allergy to any of the trial products or related products 15. Receipt of any investigational drug within one month prior to screening visit (Visit 1) 16. Donation of blood within one month prior to screening visit (Visit 1) 17. Participation in other trials within one month prior to screening visit (Visit 1). For Brazil only: receipt of any investigational drug within one year prior to screening visit (visit 1), unless there is a direct benefit to the research subject at the investigator`s discretion 18. Known or suspected abuse of alcohol, narcotics or illicit drugs 19. Previous treatment with insulin 454 20. Anticipated significant lifestyle changes during the study, e.g. shift work (including permanent night/evening shift workers), as well as highly variable eating habits |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c after 26 weeks of treatment (analysed by central laboratory). |
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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.8.3 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 | Information not present in EudraCT |
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 |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |