study to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of lcz696 followed by a 52-week, double-blind study of lcz696 compared with enalapril in pediatric patients with heart failure

Conditions: Pediatric Heart Failure

Summary: this study consists of two parts (part 1 and part 2). the purpose of part 1 is to evaluate the way the body absorbs, distributes, metabolizes and removes the drug lcz696. this will help determine the proper dose of lcz696 for part 2 of the study. the purpose for part 2 is to compare the effectiveness and safety of lcz696 with enalapril in a double-blind manner, in pediatric heart failure patients over 52 weeks of treatment.

this study consists of two parts (part 1 and part 2). the purpose of part 1 is to evaluate the way the body absorbs, distributes, metabolizes and removes the drug lcz696. this will help determine the proper dose of lcz696 for part 2 of the study. the purpose for part 2 is to compare the effectiveness and safety of lcz696 with enalapril in a double-blind manner, in pediatric heart failure patients over 52 weeks of treatment.

Eligibility criteria:
key inclusion criteria: * chronic heart failure (chf) resulting from left ventricular systolic dysfunction, and receiving chronic hf therapy (if not newly diagnosed) * new york heart association (nyha) classification ii-iv (older children: 6 to \<18 years old) or ross chf classification ii-iv (younger children: \< 6 years old) * systemic left ventricular ejection fraction ≤ 45% or fractional shortening ≤22.5% * for part 1 study: patients must be treated with an angiotensin converting enzyme inhibitor (acei) or angiotensin receptor blockers (arb) prior to screening. patients in group 1 and 2 must be currently treated with the dose equivalent of at least enalapril 0.2 mg/kg prior to the lcz696 3.1 mg/kg administration. group 3 patients will participate in lcz696 0.8 mg/kg and not lcz696 3.1 mg/kg. * biventricular physiology with systemic left ventricle key exclusion criteria: * patient with single ventricle or systemic right ventricle * patients listed for heart transplantation (as united network for organ sharing status 1a) or hospitalized waiting for transplant (while on inotropes or with ventricular assist device) * sustained or symptomatic dysrhythmias uncontrolled with drug or device therapy * patients that have had cardiovascular surgery or percutaneous intervention to palliate or correct congenital cardiovascular malformations within 3 months of the screening visit. patients anticipated to undergo corrective heart surgery during the 12 months after entry into part 2 * patients with unoperated obstructive or severe regurgitant valvular (aortic, pulmonary, or tricuspid) disease, or significant systemic ventricular outflow obstruction or aortic arch obstruction * patients with restrictive or hypertrophic cardiomyopathy * active myocarditis * renal vascular hypertension (including renal artery stenosis) * moderate-to severe obstructive pulmonary disease * serum potassium \> 5.3 mmol/l * history of angioedema * allergy or hypersensitivity to acei / arb

Keywords: pediatric heart failure, systemic left ventricle, reduced ejection fraction