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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 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 |
To investigate the effects of two single subcutaneous lixisenatide doses (5 and 10 µg) as compared to placebo in reducing postprandial glucose (PPG) in type 2 diabetic paediatric population (10-17 years old) and adults as controls |
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E.2.2 | Secondary objectives of the trial |
To evaluate in both paediatric and adult populations:
- the blood levels of lixisenatide (pharmacokinetic) parameters in plasma after single subcutaneous ascending doses
- the maximum post-prandial glucose excursion, and on the changes in insulin, C-peptide and glucagon plasma concentrations following a standardized breakfast
- safety and tolerability. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients with type 2 diabetes mellitus, as defined by WHO (fasting plasma glucose ≥ 7 mmol/L (126mg/dL) or 2 hours postprandial plasma glucose ≥ 11.1 mmol/L (200 mg/dL)), diagnosed for at least 1 year (adults) and at least 3 months for paediatric population at the time of screening visit, with or without metformin (stable dose ± 10 % for at least 4 weeks prior to randomization)
- HbA1c ≥ 7% and ≤ 10% at screening
- Age eligibility for paediatric population: ≥ 10 years and <18 years with at least 3 patients below 15 years and no more than 3 patients aged between 16 and 18 years; Age eligibility for adults: ≥ 18 and ≤ 65 years
- For paediatric population: body weight > 50 kg; BMI > 85th percentile
for age and gender and ≤ 50 kg/m2
For adults: body weight > 50 kg; BMI > 25 kg/m2 and ≤ 37 kg/m2 |
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E.4 | Principal exclusion criteria |
If female, pregnancy (defined as positive serum pregnancy test), breast-feeding
Diabetes other than type 2 diabetes
Positive test for insulinoma associated protein (IA2) and glutamic acid decarboxylase (GAD) autoantibodies
Use of other oral or injectable antidiabetic or hypoglycemic agents other than metformin (e.g., alpha glucosidase inhibitor, exenatide, DPP-IV inhibitors, insulin etc.) within 3 months prior to the time of screening
Allergic reaction to any GLP-1 agonist in the past (e.g. exenatide, liraglutide) or to metacresol
History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g., multiple endocrine neoplasia syndromes)
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E.5 End points |
E.5.1 | Primary end point(s) |
GLU-AUC0:30-4:30h: area under the plasma glucose concentration time profile from time of the standardized breakfast start (30 min after IMP injection and pre-meal plasma glucose) until 4 hours later subtracting the pre-meal value |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
D1 at each period up to 4h30 after study drug injection (8 timepoints) |
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E.5.2 | Secondary end point(s) |
- Pharmacokinetics: lixisenatide plasma concentration
- Pharmacokinetic parameter (Cmax)
- Pharmacokinetic parameter (Tmax)
- Pharmacokinetic parameter (AUClast)
- Pharmacokinetic parameter (AUC)
- Area under the concentration time profile from time of standardized breakfast start (30 min after IMP injection and pre-meal plasma glucose) until 4 hours later for insulin, C-peptide and glucagon |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Pharmacokinetics: lixisenatide plasma concentration : D1 at each period up to 6h30 after study drug injection (8 timepoints)
- Others Pharmacokinetic parameters : D1 at each period
- Area under the concentration time profile from time of standardized breakfast start (30 min after IMP injection and pre-meal plasma glucose) until 4 hours later for insulin, C-peptide and glucagon: D1 at each period up to 4h30 after study drug injection (7 timespoints) |
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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 | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Tolerability, PK and PD in pediatric and adult patients |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
Mexico |
South Africa |
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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |