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 | 10067585 |
E.1.2 | Term | Type 2 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 |
The primary objective of this trial is to confirm efficacy of step-wise addition of bolus insulin in terms of glycaemic control assessed by change in HbA1c. This is done by comparing the difference in change from baseline in HbA1c after 32 weeks of treatment/end of trial between step-wise addition of bolus insulin versus complete basal-bolus therapy using a non-inferiority approach. |
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E.2.2 | Secondary objectives of the trial |
• To assess and compare efficacy in terms of: Fasting plasma glucose (FPG) values 7-point Self Measured Plasma Glucose (SMPG) Profile • To assess and compare safety and tolerability in terms of: Hypoglycaemic episodes Adverse events Clinical and laboratory assessments Change in body weight and body mass index (BMI) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female ≥18 years of age • Type 2 diabetes (diagnosed clinically) for ≥12 months • Basal insulin treatment (NPH once or twice daily, insulin glargine once daily or insulin detemir once daily) ≥ 6 months • HbA1c 7.0-9.0 % (both inclusive) by central laboratory analysis (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive) • BMI < 40.0 kg/m^2
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E.4 | Principal exclusion criteria |
• Previous use of pre-mix or bolus insulin (allowed is previous use of bolus insulin only in case of a hospitalisation or a severe condition requiring intermittent use of bolus insulin for less than 14 consecutive days, but not during the last 6 months prior to screening visit (Visit 1) • Use of GLP-1 receptor agonists or pramlintide within the last 6 months prior to screening visit (Visit 1) • Anticipated change in concomitant medication known to interfere significantly with glucose metabolism (e.g. systemic corticosteroids, beta-blockers, MAO inhibitors, etc.) • Cardiovascular disease, within the last 12 months prior to screening visit (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. • Uncontrolled treated/untreated severe hypertension (systolic blood pressure sitting ≥ 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure ≥ 100 mmHg). For Argentina: systolic blood pressure sitting ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg • Impaired liver function, defined as ALAT ≥ 2.5 times upper limit of normal (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive). • Impaired renal function defined as serum creatinine >135 μmol/L (>1.5 mg/dL) for males and >110 μmol/L ( >1.2 mg/dL) for females; and, if required by the locally applicable metformin label, glomerular filtration rate below 60 ml/min, calculated by the Cockroft & Gault formula). One retest within a week is permitted with the result of the last sample being conclusive. • Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode, during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months. • Proliferative retinopathy or maculopathy requiring treatment according to the Investigator • Treatment with OADs contraindicated or unapproved for combination treatment with insulin (according to local OAD label)
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c from baseline to week 32/end of trial |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Two different combinations of the two trial products |
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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 | 10 |
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 | 9 |
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 | 9 |