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 | 12.0 |
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 SIAC OD + metformin ± pioglitazone ± DPP-4 inhibitors 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 between SIAC OD + metformin ± pioglitazone ± DPP-4 inhibitors and insulin glargine OD + metformin ± pioglitazone ± DPP-4 inhibitors 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 SIAC OD + metformin ± pioglitazone ± DPP-4 inhibitors over insulin glargine + metformin ± pioglitazone ± DPP-4 inhibitors after 26 weeks of treatment in terms of • Prandial plasma glucose (PG) increment • Frequency of responders for HbA1c (<7%) without hypoglycaemic episodes • Fluctuation in nocturnal interstitial glucose (IG) • Nocturnal hypoglycaemic episodes • Body weight To compare efficacy and safety after 26 weeks of treatment in terms of: • Fasting plasma glucose (FPG) from central laboratory • 9-point self measured plasma glucose (SMPG) profile • SMPG for dose adjustments • Frequency of responders for HbA1c • Glucose profile as measured with CGM in a sub-population • Insulin dose • Adverse events • Hypoglycaemic episodes • Clinical and laboratory assessments • Patient reported outcome
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Informed consent obtained before any trial-related activities. (Trial related activities are defined as any procedures that would not have been performed during standard management of the subject). • Male or female ≥ 18 years of age • Type 2 diabetes mellitus (diagnosed clinically) for ≥ 6 months • Treatment with basal insulin regimen (insulin detemir, insulin glargine or neutral protamine Hagedorn [NPH] insulin) OD, for at least 3 months • Ongoing treatment with: metformin with or without other OADs for at least 3 months prior to randomisation • HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis • BMI ≤ 40.0 kg/m²
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E.4 | Principal exclusion criteria |
• Treatment with insulin regimens other than a basal insulin regimen (insulin detemir or insulin glargine or NPH insulin) OD within 3 months prior to Visit 1 • Total daily insulin dose above 1 U/kg • Treatment with glucagon-like peptide 1(GLP-1) receptor agonists within 3 months prior to visit 1 • Current rosiglitazone users • Anticipated significant lifestyle changes during the study, e.g. shift work (including permanent night/evening shift workers), as well as highly variable eating habits • Cardiovascular disease, within the last 6 months prior to visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty |
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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 | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | 11 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 11 |