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 | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
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 |
1. To investigate how Lixisenatide lowers blood glucose after feeding.
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E.2.2 | Secondary objectives of the trial |
2. To investigate the effects of Lixisenatide on the contributions of fat coming from the intestine and fat coming from the liver to the raised levels of fat found in blood after feeding in patients with type II diabetes. 3. To investigate the effects of Lixisenatide on the rate at which food is absorbed from the gut. 4. To investigate the activity of a protein which is involved in fat breakdown. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects with type 2 diabetes inadequately controlled by metformin • Stable over last 3 months • Caucasian • Male • 40-65 years • HbA1c 7.5-8.5% • BMI 30-35 • Able and willing to self-administer placebo/lixisenatide injection • Able and willing to perform self-blood glucose monitoring.
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E.4 | Principal exclusion criteria |
• Subjects treated with insulin, any oral hypoglycaemic agents (OHA) other than metformin, any insulin secretagogues • A history of heavy alcohol use (>12 to 15 g of alcohol per day), • Arteriopathy • Hepatic disease-with ALT >3 times upper limit of normal • Renal disease-estimated glomerular filtration rate less than 40ml/minute. • Subjects receiving fibrates or weight reducing drugs, • Mental incapacity, • Unwillingness or a language barrier precluding adequate understanding or co-operation • Fasting plasma triglycerides >4.0 mmol/l • Blood pressure limits Systolic <160 mmHg • Laboratory findings at the time of screening, including amylase and/or lipase > 3 times the upper limit of the normal laboratory range (ULN) and P-calcitonin ≥20 pg/ml (5.9 pmol/L). • Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes). • History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, • Allergic reaction to any GLP-1 receptor agonist or to metacresol. • Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting. • Patients on beta blockers. • Smokers |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint The total rate of glucose appearance following the breakfast meal at visits 3 and 7, measured as area under the curve (AUC) from 0-180 minutes and AUC from 0-240 minutes, where the meal is given at 0 minutes.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
180 minutes and 240 minutes where the meal is given at 0 minutes. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints At visits 3 and 7 • endogenous glucose production measured as AUC (0-180 minutes) and AUC (0-240 minutes) • rate of meal glucose appearance measured as AUC (0-180 minutes) and AUC (0-240 minutes) • glucose clearance rate measured as AUC (0-180 minutes) and AUC (0-240 minutes) • postprandial glycaemia measured as AUC (0-180 minutes) and AUC (0-240 minutes) • the rate of gastric emptying • post-heparin lipoprotein lipase activity At visits 4 and 8 • the production rate of chylomicrons • the production rate of VLDL • the clearance rate of chylomicrons • the clearance rate of VLDL • postprandial triglyceridaemia (AUC- visits 3 and 7; steady state TGs - visits 4 and 8) • energy intake measured by diet diary
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Understanding mechanism of action |
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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.8.2.4 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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When all the laboratory analysis is completed. |
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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 | 3 |
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 | 0 |
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 |