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 | 10045228 |
E.1.2 | Term | Type I 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 compare the pharmacokinetic and pharmacodynamic profile of the rapid-acting insulin analogue aspart (novorapid®) injected subcutaneously with jet-injection to that of the same insulin injected with a conventional pen in people without diabetes and in people with type 1 diabetes mellitus. Main study endpoint: Pharmacodynamic profile of insulin, based on parameters of the exogenous glucose infusion rate (GIR, in ml/min/kg) required to maintain euglycaemia |
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E.2.2 | Secondary objectives of the trial |
Secondary study endpoint: Pharmacokinetic profile of insulin, based on plasma insulin levels |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The study entails three sub-studies that will be executed consecutively. These sub-studies are:
Sub-study 1: This sub-study will be conducted in healthy non-diabetic volunteers. Novorapid will be administered at a dose of 0.2 units per kg body weight.
Sub-study 2: This sub-study will be conducted in healthy non-diabetic volunteers. Novorapid will be administered at a dose of 0.4 units per kg body weight.
Sub-study 3: This sub-study will be conducted in people with type 1 diabetes mellitus. Novorapid will be administered at a dose of 0.4 units per kg body weight.
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E.3 | Principal inclusion criteria |
Inclusion criteria for healthy subjects • Age 18-50 years • Body-mass index 18-28 kg/m2 • Blood pressure <160/90 mmHg Inclusion criteria for patients with type 1 diabetes • Age 18-50 years • Body-mass index 18-28 kg/m2 • Stable glycaemic control with HbA1c 6.5-9.0% • Duration of diabetes >1 year • Blood pressure <160/90 mmHg |
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E.4 | Principal exclusion criteria |
Exclusion criteria for healthy subjects • Inability to provide informed consent • Chronic use of medication other than oral contraceptives or thyroid hormone replacement therapy (with stable euthyroidism for at least 3 months) • Type 2 diabetes in first-degree relatives • History of a major cardiovascular disease event (myocardial infarction, stroke, symptomatic peripheral artery disease, coronary bypass surgery, percutaneous coronary or peripheral artery angioplasty) • Pregnancy Exclusion criteria for patients with type 1 diabetes • Inability to provide informed consent • Chronic use of medication other than insulin, oral contraceptives, thyroid hormone replacement therapy (with stable euthyroidism for at least 3 months), or low-dose angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) treatment • Macroalbuminuria, i.e. urinary albumin excretion >200 g/min in collected urine sample or urinary albumin-to-creatinine ratio >300 mg/g in spot urine sample • Symptomatic diabetic neuropathy • Proliferative diabetic retinopathy (a history of proliferative retinopathy that was successfully treated with laser coagulopathy is not an exclusion criterion) • History of a major cardiovascular disease event (myocardial infarction, stroke, symptomatic peripheral artery disease, coronary bypass surgery, percutaneous coronary or peripheral artery angioplasty) • Pregnancy |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacodynamic profile of insulin, based on parameters of the exogenous glucose infusion rate (GIR, in ml/min/kg) required to maintain euglycaemia: - Cmax (mg/min): maximal GIR during the 8-hour study (from timepoint 0) - Tmax (min): time to maximal GIR - AUC (g): area under the curve for GIR during the 8-hour study (from timepoint 0) - TAUC½ (min): time of 50% of glucose disposal, i.e. the median of the GIR profile
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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last visit of the last subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |