Healthy subjects between 25 and 65 years old MedDRA version: 18.0 Level: HLT Classification code 10007574 Term: Cardiac imaging procedures System Organ Class: 10022891 - Investigations MedDRA version: 18.0 Level: PT Classification code 10052677 Term: Vascular imaging System Organ Class: 10022891 - Investigations MedDRA version: 18.0 Level: PT Classification code 10006093 Term: Bradycardia System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: PROCORALAN
Pharmaceutical Form: Capsule
INN or Proposed INN: Ivabradine
CAS Number: 148849-67-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharm
Sponsors
CHU - Hôpitaux de Rouen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Healthy subject • Aged between 25 and 65 years old • Caucasian • Resting heart rate mesured three times after a rest period of 15 min = 70 bpm • No significant ECG abnormality • No significant biological abnormality • Childbearing age women must have effective contraception (estrogen-progestin contraceptives, intrauterin device or tubal ligation). Will be considered postmenopausal women with amenorrhea for more than 2 years • Able to read and understand information form and to give written informed consent • Subjects with medical insurance Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Subjects who don’t understand French language • Subjects deprived of liberty by an administrative or judicial decision or protected adult subject (under guardianship) • Pregnant women, nursing mother or women without contraception • Subjects who participate to an other trial / participated to an other interventional research without drugs during the last month or a trial with drugs during the last 3 months • Hypersensitivity to the active substance or to any of the excipients • Congenital galactosemia, lactase deficiency (Lapp), malabsorption of glucose and galactose • Severe hypotension, mesured three times after a rest period of 15 min (5 cigarettes/day) • Severe hypercholesterolemia (Total cholesterol >2,5 g/L) • Subjects who practice sports intensively (= 1 hour/day) • Renal insufficiency (creatinine clearance = 60 ml/min/1,73 m² Cockroft and Gault formula) • Known liver failure • Known heart failure or suspected heart failure (congestive episode) • Atrial fibrillation • High-grade conduction block (Sick sinus syndrome, sino-atrial block or grade 2 or 3 atrio-ventricular block) • Abnormal corrected QT with Bazett formula (cQT > 450 ms (men) or > 470 ms (women)). • Pacemaker • All cardiac or no cardiac diseases, active or with sequelae, which, in the opinion of the investigator, is accompanied by a risk of cardiac or vascular abnormality • Known retinal disease • Subject disagrees with the prohibition of taking grapefruit juice, millepertuis or any medication during the study except oral contraceptive, acetaminophene or decision of the investigator. (annex n°02) • Administration of any medication listed in anex n°02 (aspirin, NSAID and inhibitors of cytochrome P450 3A4) during the previous week.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of heart rate reduction after repeated administration of ivabradine on wall viscosity of the common carotid artery in healthy subjects;Secondary Objective: - To assess the effect of heart rate reduction after repeated administration of ivabradine on vascular geometry and function, and cardiovascular haemodynamics in healthy subjects - To assess the role of aging on the effect of heart rate reduction after repeated administration of ivabradine on all these parameters in healthy subjects ;Primary end point(s): Magnitude of change in wall viscosity of the common carotid artery after repeated administration of ivabradine and placebo in healthy subjects.;Timepoint(s) of evaluation of this end point: This study contain five visits. At each visit, from the first (V1) to the fourth visit (V4), the primary criteria will be evaluated. In fact, vascular echotracking and applanation tonometry will enable us to evaluate the primary criteria during the first(two to ten days after inclusion visit), second (6 days after V1), third (12 to 16 days after V2) and fourth (6 days after V3) visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Magnitude of change in diameter, intima-media thickness and carotid distensibility and carotid to femoral pulse wave velocity after repeated administration of ivabradine and placebo in healthy subjects . - Magnitude of change in plasma levels of biomarkers of endothelial function and in endothelial shear stress after repeated administration of ivabradine and placebo in healthy subjects - Magnitude of change in peripheral and central pressures, augmentation index, Buckberg index and cardiac output after repeated administration of ivabradine and placebo in healthy subjects. - Relationship between age and the magnitude of change in all previous parameters after repeated administration of ivabradine and placebo, in healthy subjects.;Timepoint(s) of evaluation of this end point: The examinations which will allow to assess these secondary criteria are : -Applanation tonometry -Vascular echo-tracking -Automated velocimetry -Biological examination -High Resolution Doppler -Vascular oscillometry -Bio-impedancemetry This study contain five visits. At each visit, from the first (V1) to the fourth visit (V4), the secondary cirteria will be evaluated : -First visit (V1), two to ten days after inclusion visit, -Second visit(V2), 6 days after V1, -Third visit (V3), 12 to 16 days after V2, -Fourth visit (V4), 6 days after V3. | — |
Countries
France
Contacts
Public ContactMEYOHAS
Délégation à la recherche clinique et à l'innovation
Outcome results
None listed