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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of this study is to compare the insulin sensitivity in volunteers with type 2 diabetes during a continuous infusion (pyr1) -Apeline-13 versus a placebo infusion. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to: 1) Get the tolerance and safety data for the administration of (pyr1) -Apeline-13 in humans, complementing data from published and ongoing studies, 2) Measure the plasma concentration of apelin depending on the administered dose, 3) Perform a serum bank for hormonal and metabolic posteriori trials (insulin, glucagon, apelin, other cytokines and hormones involved in energy metabolism). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient aged 40-65 years.
Type 2 diabetes
Diabetes treated with oral antidiabetic agents only
BMI between 27 and 33 Kg / cm².
HbA1c <8.5%
Non-pathological ECG
Resting heart rate of between 50 and 80 beats per minute
Complete Blood Count (CBC) without clinically significant abnormalities in terms of the investigator.
Liver function tests without clinically significant abnormalities in terms of the investigator.
Renal function tests without clinically significant abnormalities in terms of the investigator .
Serum electrolytes without clinically significant abnormalities in terms of the investigator.
Good peripheral venous system (forearm and back of the hand)
Acceptance to participate in the establishment of a serum bank
Ability to sign an informed consent.
Affiliation to a social security scheme or equivalent. |
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E.4 | Principal exclusion criteria |
Patients experiencing secondary cardiovascular prevention.
Diabetes treated by insulin or GLP-1 in the 6 months prior to inclusion
Risk factor, treatment or ECG as recommended ICH E14 "Clinical Evaluation of QT / QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs":
- Repeated measurement of a QTc interval> 450 ms
- Torsade de pointes risk factor: myocardial infarction, hypokalemia, family history of long QT syndrome
Personal history of cancer.
Positive HIV serology.
Hepatitis B serology positive.
Hepatitis C serology positive.
Cognitive impairment or mental illness (at the discretion of the investigator)
Excessive alcohol chronic use (consumption> 30g / day or 210g / week)
Subject having a systolic blood pressure greater than the rest to 140 mm Hg and 90 mm Hg diastolic
Smoking> 10 cig / day and can not be interrupted during 24 hours
About participating in another research protocol or exclusion period from another protocol
Nobody in safeguarding justice, guardianship |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the measure of the difference between recent glucose infusion rate measured in the last 30 minutes of a hyperinsulinemic euglycemic clamp in the presence of a continuous infusion (pyr1) -Apeline-13 infusion rate glucose measured under the same conditions in the presence of a continuous infusion of placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
in the last 30 minutes of a hyperinsulinemic euglycemic clamp |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are:
- Calculation of the M factor (glucose metabolism) according ref De Fronzo (12, 37)
- Variations of the measurement of the systolic blood pressure
- Variations of the measurement of the diastolic blood pressure
- Changes in heart rate measurement
- Route of ECG Changes
- Clinical signs of intolerance / allergy / toxicity
- Determination of plasma insulin
- Determination of glucagon
- Determination of apelin
- Determination of leptin
- Determination of adiponectin |
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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 | 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) | 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) | 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.8.5 | 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 | Yes |
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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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |