Paediatric dilated cardiomyopathy and symptomatic chronic heart failure MedDRA version: 16.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: S16257-2
Product Code: S16527-2
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivabradine
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Concentration unit: mg mill
Sponsors
Institut de Recherches Internationales Servier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Patients of both gender aged from 6 months to less than 18 years old -Patients with dilated cardiomyopathy (DCM) receiving their usual treatment for chronic heart failure (CHF) at the optimal dose -Patients in sinus rhythm Resting heart rate (HR) complying with the following criteria: .HR >= 105 bpm in the age-subset [6-12[ months .HR >= 95 bpm in the age-subset [1-3[ years .HR >= 75 bpm in the age-subset [3-5[ years .HR >= 70 bpm in the age-subset [5-18[ years. -CHF class II to IV NYHA or Ross classification, stable for at leas 1 month prior to selection Left ventricular (LV) dysfunction with LVEF =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Class I NYHA or Ross Classification (asymptomatic patients), •A girl having childbearing potential and sexually active not having contraceeption •History of symptomatic or sustained (= 30 sec) ventricular arrhythmia unless a cardioverter defibrillator was implanted, •Patients with structural valvular disease or severe functional valvular disease requiring surgery, •Significant systemic ventricular outflow obstruction, •DCM secondary to muscular dystrophies, hemoglobinopathies, HIV, carnitine deficiency •Patients requiring unauthorised concomitant treatment •Serum creatinine >2.0 mg/dL or >180 µmol/L (blood sample performed at ASSE visit), •AST and/or ALT > 3 upper normal limits (blood sample performed at ASSE visit), •Unstable cardiovascular conditionat selection or inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the optimal dose of ivabradine to reach the target heart rate reduction (HRR) of 20% without inducing a bradycardia (i.e. HR should be greater than a predefined HR threshold by age subset) and/or signs or symptoms related to bradycardia, To assess the pharmacokinetic (PK) parameters of ivabradine and its active metabolite S 18982 after repeated oral administrations, To assess the PKPD relationship of ivabradine and its active metabolite S 18982 using heart rate as evaluation criterion. ;Secondary Objective: To assess, compared to placebo, the effects of ivabradine at target dose, on: .left ventricular ejection fraction, measured by echocardiography, .clinical symptoms by using the NYHA/ROSS classification, .global clinical status evaluated by the investigator/parents, .cardiovascular biomarker by measuring NT-proBNP, To assess, compared to placebo, the long-term safety of ivabradine over 1-year. ;Primary end point(s): -Characterization PK and PKPD -Target HR achievement;Timepoint(s) of evaluation of this end point: PK measurements: at D014 and M000 Heart rate reduction (HRR): HR measurements during titration period (D000, D014, D028, D042, D056, M000) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Echocardiographic parameters -Heart failure symptoms severity -Cardiovascular biomarker NT- proBNP. -Safety ;Timepoint(s) of evaluation of this end point: over the study | — |
Countries
Australia, Brazil, Denmark, Finland, Germany, Hungary, Italy, Mexico, Portugal, Russian Federation, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical Studies Department
Institut de Recherches Internationales Servier
Outcome results
None listed