E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 1 |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.0 |
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 |
To compare the rates of severe or BG (blood glucose) confirmed symptomatic hypoglycaemia of IDeg once daily (OD) + IAsp to IGlar OD + IAsp, by demonstrating that the upper limit of the 95% confidence interval of the rate ratio is below or equal to a non-inferiority margin of 1.10, and if confirmed, to a superiority limit of 1.0 |
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E.2.2 | Secondary objectives of the trial |
To compare the rates of severe or BG confirmed symptomatic nocturnal hypoglycaemia with IDeg OD + IAsp to IGlar OD + IAsp, by demonstrating that the upper limit of the 95% confidence interval of the rate ratio is below or equal to a non-inferiority margin of 1.10, and if confirmed, to a superiority limit of 1.0.
To confirm superiority of IDeg OD + IAsp compared to IGlar OD + IAsp in terms of proportion of subjects with severe hypoglycaemic episodes.
To compare efficacy of IDeg OD + IAsp in controlling glycaemia with respect to change from baseline in HbA1c after 32 weeks of treatment. This is done by comparing the difference in change from baseline in HbA1c after 32 weeks of treatment between IDeg OD + IAsp and IGlar OD + IAsp to a non-inferiority limit of 0.4%.To compare IDeg OD + IAsp and IGlar OD + IAsp in terms of safety, other parameters of glycaemic control and patient reported outcome (PRO). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, age ≥ 18 years at the time of signing informed consent
2. Subjects fulfilling at least one of the below criteria:
a) Experienced at least one severe hypo episode within the last year (according to the ADA definition, April 2013)
b) Moderate chronic renal failure, defined as glomerular filtration rate 30 - 59 mL/min/1.73 m^2 per CKD-Epi
c) Hypoglycaemic symptom unawareness
d) Diabetes mellitus duration for more than 15 years
e) Recent episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (≤ 70 mg/dL [≤ 3.9 mmol/L])) within the last 12 weeks prior to Visit 1 (screening)
3. Type 1 diabetes mellitus (diagnosed clinically) ≥ 52 weeks prior to Visit 1
4. Current treatment with a basal−bolus regimen (consisting of neutral protamine Hagedorn (NPH) insulin OD / BID or insulin detemir (IDet) OD / BID plus 2−4 daily injections of any rapid acting or fast acting meal time insulin) or CSII (with rapid acting insulin) for ≥ 26 weeks prior to Visit 1
5. HbA1c ≤ 10% by central laboratory analysis
6. BMI ≤ 45 kg/m^2 |
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E.4 | Principal exclusion criteria |
1. Treatment with IGlar or IDeg within the last 26 weeks prior to Visit 1 (short term use [≤ 2 weeks] is allowed, but not within 4 weeks prior to screening)
2. Use of any other anti-diabetic agent than those stated in the inclusion criteria within the last 26 weeks prior to Visit 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of treatment emergent severe or BG (blood glucose) confirmed symptomatic hypoglycaemic episodes during the maintenance period.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64) |
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E.5.2 | Secondary end point(s) |
1. Number of treatment emergent severe or BG confirmed symptomatic nocturnal hypoglycaemic episodes during the maintenance period.
2. Proportion of subjects with one or more severe hypoglycaemic episodes during the maintenance period.
3. Incidence of treatment emergent adverse events.
4. Change from baseline in HbA1c (glycosylated haemoglobin).
5. FPG (Fasting plasma glucose).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)
2. After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)
3. During 32 weeks of treatment for each treatment period
4. Week 32, Week 64
5. Week 32, Week 64
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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 | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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
| 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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
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 |
European Union |
United States |
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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 | 4 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 29 |