E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
Comparison of postprandial blood glucose (BG) control after administration of BC222 insulin Lispro (BC Lispro) and Humalog® at the start (t=0) of a standardised meal ingestion |
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E.2.2 | Secondary objectives of the trial |
Comparison of the postprandial pharmacokinetic profiles of BC222 insulin lispro and Humalog® when injected after a standardized meal |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subject aged 18-64 years (both inclusive).
2. Type 1 diabetes mellitus (as diagnosed clinically) >= 12 months.
3. Treated with multiple daily insulin injections or CSII >= 12 months.
4. Current total daily insulin treatment < 1.2 (I)U/kg/day.
5. BMI 18.5-28.0 kg/m^22 (both inclusive).
6. HbA1c <= 9.0% by local laboratory analysis (one retest within a week is permitted with the result of the last test being conclusive).
7. Fasting C-peptide <= 0.3 nmol/L.
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E.4 | Principal exclusion criteria |
1. Known or suspected hypersensitivity to trial products or related products.
2. Type 2 diabetes mellitus.
3. Previous participation in this trial. Participation is defined as randomised.
4. The receipt of any trial product within 60 days prior to this trial.
5. Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis screening tests, as judged by the Investigator considering the underlying disease.
6. Presence of clinically significant acute gastrointestinal symptoms (e.g. nausea, vomiting, heartburn or diarrhoea), as judged by the Investigator.
7. Known slowing of gastric emptying and or gastrointestinal surgery that in the opinion of the investigator might change gastrointestinal motility and food absorption.
8. Unusual meal habits and special diet requirements or unwillingness to eat the food provided in the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
AUCBG,0-2h, area under the blood glucose concentration-time curve from 0-2 hours after a standardised meal |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
0-2 h after trial drug administration |
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E.5.2 | Secondary end point(s) |
Secondary Pharmacodynamic Endpoints:
• AUCBG,0-8h, area under the blood glucose concentration-time curve from 0-8 hours after a standardised meal
• AUCBG,0-1h, area under the blood glucose concentration-time curve from 0-1 hours after a standardised meal
• ΔBGmax, maximum blood glucose excursion after a standardised meal (0-8 hours)
• BGmax, maximum blood glucose concentration after a standardised meal (0-8 hours)
• tBGmax, time to maximum blood glucose concentration after a standardised meal (0-8 hours)
• ΔBGmin, minimum blood glucose excursion after a standardised meal (0-8 hours)
• BGmin, minimum blood glucose concentration after a standardised meal (0-8 hours)
• BG1h, blood glucose concentration at 1 hour after a standardised meal (0-8 hours)
• BG2h, blood glucose concentration at 2 hours after a standardised meal (0-8 hours)
• AUCFFA,0-8h, area under the free fatty acid concentration-time curve from 0-8 hours after a standardised meal
• FFAmin, minimum free fatty acid concentration after a standardised meal (0-8 hours)
• tFFAmin, time to the minimum free fatty acid concentration after a standardised meal (0-8 hours)
Secondary pharmacokinetic Endpoints :
• AUCILisp,0-8h, area under the serum insulin lispro concentration-time curve from 0-8 hours
• AUCILisp,0-30min, area under the serum insulin lispro concentration-time curve from 0-30 min
• AUCILisp,0-1h, area under the serum insulin lispro concentration-time curve from 0-1 hours
• AUCILisp,0-∞, area under the serum insulin lispro concentration-time curve from 0 to infinity
• tmax,ILisp, time to maximum observed serum insulin lispro concentration
• Early t[0.5max(/Lisp)] Time to first observed half maximum serum insulin /lispro concentrations
• Late t[0.5max(Lisp)] Time to last observed half maximum serum insulin lispro concentrations
• Cmax,ILisp, maximum observed serum insulin lispro concentration
• t1/2, ILisp, terminal half-life for insulin lispro
Safety:
• Adverse events
• Local tolerability at the injection site
• Laboratory safety variables (haematology, biochemistry, lipids, urinalysis)
• Physical examination
• Vital signs
• Electrocardiogram
• Hypoglycaemic episodes
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From 0-30min up to 0-8h after trial drug Administration, as given above
Safety: ongoing |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |