E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes mellitus type 2 Diabetes mellitus tipo 2 |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II 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 ± OAD(s) in controlling glycaemia with respect to change from baseline in HbA1c after 52 weeks of treatment. This is done by comparing the difference in change from baseline in HbA1c after 52 weeks of treatment between SIBA + insulin aspart ± OAD(s) and insulin glargine + insulin aspart ± OAD(s) 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 ± OAD(s) to insulin glargine + insulin aspart ± OAD(s) after 52 weeks of treatment in terms of: • Hypoglycaemic episodes • FPG from central laboratory • Within-subject variability in self-measured FPG • Frequency of responders for HbA1c without hypoglycaemic episodes To compare efficacy and safety in terms of: • Frequency of responders for HbA1c • 9-point profile (SMPG) • Insulin dose • Body weight • AEs • Hypoglycaemic episodes • Clinical and laboratory assessments • Cardiovascular risk markers • PRO |
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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 standard management of the subject) 2. Male or female, age ≥ 18 years 3. Type 2 diabetes mellitus (diagnosed clinically) ≥ 6 months 4. Current treatment with any insulin regimen (premix, self-mix, basal only, basal bolus (one or more boluses), bolus only, pump) for at least 3 months +/- OADs prior to Visit 1 5. HbA1c 7.0 – 10.0% (both inclusive) by central laboratory analysis 6. BMI ≤ 40.0 kg/m2 7. Ability and willingness to adhere to the protocol including performance of SMPG profiles according to the protocol. |
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E.4 | Principal exclusion criteria |
1. Use within the last 3 months prior to Visit 1 of: GLP-1 receptor agonist (exenatide, liraglutide) and/or rosiglitazone 2. Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as systemic corticosteroids, beta-blockers, MAO inhibitors 3. Off-label use of any concomitant medication, including OADs to be continued in the trial 4. For pioglitazone user: clinically significant peripheral oedema or contraindications/restrictions to pioglitazone use 5. Cardiovascular disease, within the last 6 months prior to visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA)29 class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty. 6. Uncontrolled treated/untreated severe hypertension (systolic blood pressure ≥ 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure ≥ 100 mmHg) 7. Impaired liver function, defined as alanine aminotransferase (ALAT) ≥ 2.5 times upper limit of normal (one retest analysed at the central laboratory within a week of receipt of the result is permitted with the result of the last sample being conclusive)8. Impaired renal function defined as serum-creatinine ≥ 125 µmol/L (≥ 1.4 mg/dL) for males and ≥ 110 µmol/L (≥ 1.3 mg/dL) for females or according to local label for metformin use. One retest within a week of receipt of the result is permitted with the result of the last sample being conclusive 9. Recurrent (more than 1 severe hypoglycaemic event per year) severe hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months 10. Proliferative retinopathy or maculopathy requiring treatment according to the Investigator 11. Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements (for Germany: implants, injectables, combined oral contraceptives, hormonal intrauterine device (IUD), sexual abstinence or vasectomised partner) 12. Cancer and any medical history of cancer (except basal cell skin cancer or squamous cell skin cancer) 13. Any clinically significant disease or disorder, except for conditions associated with type 2 diabetes, which in the Investigator’s opinion could interfere with the results of the trial 14. Mental incapacity, psychiatric disorder, unwillingness or language barriers precluding adequate understanding or co-operation, including subject not able to read or write 15. Previous participation in this trial. Participation is defined as randomised. Re-screening for screening failures is allowed once only within the limits of the recruitment period 16. Known or suspected allergy to any of the trial products or related products 17. Receipt of any investigational drug within one month prior to Visit 1 18. Donation of blood or participation in other trials within one month prior to Visit 1 19. Known or suspected abuse of alcohol, narcotics or illicit drugs |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c after 52 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 14 |