E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II 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 confirm efficacy of treatment with meal time faster-acting insulin aspart (FIAsp) in terms of glycaemic control measured by glycosylated haemoglobin (HbA1c) after 26 weeks of randomised treatment, by comparing to meal time insulin aspart, both in combination with once daily insulin glargine and metformin, using a non-inferiority approach. |
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E.2.2 | Secondary objectives of the trial |
1. To confirm superiority of meal time FIAsp vs. meal time insulin aspart both in combination with once daily insulin glargine and metformin after 26 weeks of randomised treatment in terms of:
• Postprandial glucose (PPG) regulation
• Number of hypoglycaemic episodes
• Body weight regulation
2. To compare other efficacy and safety endpoints of meal time FIAsp with meal time insulin aspart, both in combination with once daily insulin glargine and metformin, after 26 weeks of randomised treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female or male, age ≥ 18 years at the time of signing inform consent
• Type 2 diabetes (diagnosed clinically) ≥ 6 months at time of screening (visit 1)
• Treated with basal insulin for at least 6 months prior to screening (visit 1)
• Current once daily treatment with insulin NPH, insulin detemir or glargine for at least 3 months prior to the screening visit (visit 1)
• Current treatment with:
a. metformin with unchanged dosing for at least 3 months prior to screening (visit 1). The metformin dose must be at least 1000 mg
or
b. metformin in combination with sulfonylurea (SU) or glinide or DPP-IV inhibitors and/or alpha-glucosidase inhibitors (AGI) with unchanged dosing for at least 3 months prior to screening (visit 1). The metformin dose must be at least 1000 mg
• HbA1c by central laboratory:
a. 7.0 - 9.5% (53 – 80 mmol/mol) (both inclusive) in the metformin group at the screening visit (visit 1)
or
b. 7.0 - 9.0% (53 – 75 mmol/mol) (both inclusive) in the metformin + other OAD (SU, glinide, DDP-IV inhibitors, AGI) combination group at the screening visit (visit 1)
• Body mass index (BMI) ≤ 40.0 kg/m^2
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E.4 | Principal exclusion criteria |
• Any use of bolus insulin, except short-term use due to intermittent illness (no longer than 14 days consecutive treatment) and not 3 months prior to the screening visit (visit 1)
• Use of GLP-1 agonists and/or TZDs within the last 3 months prior to screening (visit 1)
• Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months prior to screening (visit 1)
• Cardiovascular disease, within the last 6 months prior to screening (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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of randomised treatment |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in 2-hour PPG increment (meal test)
2. Number of treatment emergent confirmed hypoglycaemic episodes
3. Change from baseline in body weight |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 26 weeks of randomised treatment
2. From baseline to 26 weeks of randomised treatment
3. After 26 weeks of randomised treatment
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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 | Yes |
E.8.1.6 | Cross over | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
Canada |
Croatia |
India |
Israel |
Russian Federation |
Serbia |
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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |