Selections of Subjects With Important Changes in Their Cardiac Repolarization Parameters for the Procurement of Skin and Blood Samples

Study Overview
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Brief Summary
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The study main objective is to assess the changes in the ventricular repolarization (measure by the delta QTcf) after drug induced stimulation, compare to placebo, in order to identify subjects with extreme responses and collecting their skin and blood samples.

Detailed Description
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An ECG is performed after a dose of sotalol on about 100 healthy subjects in order to identify about 20 extreme responders (10 high responders and 10 non responders) assessed as Delta QTcf compare to baseline. The ECG will be measured and the delta QTcf will be calculated on the 20 selected subjects in a second part of the clinical trial, cross over erythromycin/placebo.

Official Title
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Selections of Subjects With Dramatic Changes in Their Cardiac Repolarization Parameters After a Pharmacologic Stimulus Aiming to Collect Their Skin Biopsy and Blood Cells

Conditions
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Cardiology: RR / QT

Intervention / Treatment
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* Drug: Erythromycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 40 years of age Caucasian origin BMI 19 to 29 kg/m² Informed Consent obtained National Health Security Number Eligible for Phase I as mentioned in the national registry of healthy volunteers For woman: use of an effective contraceptive method Non Inclusion Criteria: Asthma Heart Rate < 50 bpm Hypotension with systolic blood pressure< 100 mm Hg. atrioventricular block (PR interval > 200 ms) Known Chronic illness (hepatic, renal or cardiac impairment, etc..) Raynaud's phenomenon Drug known to prolong QT (http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm) in the last 7 days. All chronic treatments are forbidden exceptive : oral contraceptives, paracetamol, vitamins and comfort treatment that do not prolong the QT Known family or individual past history of QT prolongation or unexplained syncope (QTcF) > 450 ms QRS interval non assessable on ECG at rest or bundle-branch block, QRS > 100 ms Allergy to macrolide type antibiotics Known allergy to sotalol or lidocaine Positive blood pregnancy test (Inclusion visit) Known abnormal haemostasis Kaliemia< 3.5 mmol/L Magnesemia< 0,7 mmol/L Under exclusion period or participating to another clinical trial on a new medicinal product Creatinin clearance < 80 ml/min (Cockroft and Gault formula) AST-ALT >3x upper normal limit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erythromycin<br> | Drug: Erythromycin<br>* 4mg/Kg, IV during 20 min once<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 4mg/Kg, IV during 20 min once<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prolongation of cardiac QT due to erythromycin compare to Placebo reported as Delta QTcf | Delta QTcf is measured at H0, H0+20 minutes, and H0+1h20, on groups' erythromycin and placebo. QTcf may be adjusted based on the pharmacokinetic data to ensure time of the plasmatic pick is used. | 1hour and 20 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison Delta QTcf eryhtromycin-sotalol | compare the effect of erythromycin and sotalol on QT prologation | over 3 hours | 
| Assess the effect of erythromycin Twave morphologie changes | Analysis of Qwave morphologic changes | 1hour and 20 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug induced QT prolongation