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

Phase 1

Completed

• Conditions: Cardiology: RR / QT
• Interventions: Drug: Placebo; Drug: Erythromycin

• Registration Number: NCT01338441
• Lead Sponsor: Ectycell SASU

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-04-15
• Study First Submitted QC: 2011-04-18
• Study First Posted: 2011-04-19
• Primary Completion: 2011-05
• Study Completion: 2011-08
• Status Verified: 2011-09
• Last Update Submitted: 2011-09-14
• Last Update Posted: 2011-09-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Erythromycin	Erythromycin	-

Primary Outcome Measures

Name	Time	Method
Prolongation of cardiac QT due to erythromycin compare to Placebo reported as Delta QTcf	1hour and 20 minutes	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

BIOTRIAL; 🇫🇷 Rueil Malmaison, France