Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure aged from 6 months to less than 18 years

• Register: EUCTR
• Last refreshed on: 12 May 2014
• Main ID: EUCTR2011-001292-39-IT
• Date of registration: 28/12/2011
• Prospective Registration: No
• Primary sponsor: INSTITUT DE RECHERCHES INTERNATIONALES SERVIER
• Public title: Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure aged from 6 months to less than 18 years
• Scientific title: Determination of the efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symptomatic chronic heart failure aged from 6 months to less than 18 years. A randomised, double-blind, multicentre, placebo controlled, phase II/III dose-finding study with a PK/PD characterisation and a 1 year efficacy/safety evaluation.
• Date of first enrolment: 02/11/2011
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001292-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Brazil, Canada, Denmark, Finland, Germany, Hungary, India, Italy, Mexico, Portugal, Russian Federation, Spain, Sweden, United Kingdom

Contacts

• Name: PROJECT MANAGER - S. CECCOTTI
• Affiliation: ISTITUTO DI RICERCA SERVIER

• Name: PROJECT MANAGER - S. CECCOTTI
• Affiliation: ISTITUTO DI RICERCA SERVIER

Key inclusion & exclusion 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 least 1 month prior to selection; -Left ventricular (LV) dysfunction with LVEF <= 45% documented by echocardiography; -LV dysfunction consecutive to idiopathic DCM, post-viral myocarditis DCM or ischaemic DCM
Are the trial subjects under 18? yes
Number of subjects for this age range: 90
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Class I NYHA or Ross Classification (asymptomatic patients), •Patients actively listed for transplantation at time of entry into the study or anticipated to undergo heart transplantation or corrective heart surgery during the 1 year following entry into the study, •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, anthracyclines, •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 condition at selection or inclusion.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Paediatric dilated cardiomyopathy and symptomatic chronic heart failure
MedDRA version: 14.1 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 10007541 - Cardiac disorders
MedDRA version: 14.1 Level: SOC Classification code 10007541 Term: Cardiac disorders System Organ Class: 10007541 - Cardiac disorders

Intervention(s)

Product Name: S16257-2
Product Code: S16257-2
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IVABRADINE
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: PROCORALAN
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IVABRADINE
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: PROCORALAN
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IVABRADINE
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: S16257-2
Product Code: S16257-2
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IVABRADINE
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: S16257-2
Product Code: S16257-2
Pharmaceutical Form: Oral solution
INN or Proposed INN: IVABRADINE
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: .1-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Product Name: S16257-2
Product Code: S16257-2
Pharmaceutical Form: Oral solution
INN or Proposed INN: IVABRADINE
CAS Number: 155974-00-8
Current Sponsor code: S16257-2
Concentration unit: mg/ml milligram(s)/mil

Primary Outcome(s)

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 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.

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.

Primary end point(s): -Characterization PK and PKPD -Target HR achievement

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: over the study

Secondary end point(s): - Echocardiographic parameters -Heart failure symptoms severity - Cardiovascular biomarker NT- proBNP. -Safety

Secondary ID(s)

2011-001292-39-FI

CL2-16257-090

Source(s) of Monetary Support

ADIR