Pharmacokinetics, pharmacodynamics, safety and efficacy study of LCZ696 in children (1 month to < 18 years) with heart failure
- Conditions
- Pediatric heart failure 1 month to <18 years oldMedDRA version: 20.0Level: LLTClassification code 10019279Term: Heart failureSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2015-004207-22-BG
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 360
- Chronic heart failure resulting from left ventricular systolic dysfunction, and receiving chronic HF therapy (if not newly diagnosed)
- 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%
(assessed by most recent echocardiography, MRI, MUGA or left ventricular angiogram within 1 month before patient begins Part 2).
[Note: The study will target enrollment of approximately 80% patients with a systemic left ventricular ejection fraction (EF) = 40% or fractional
shortening =20% for Part 2 only].
- Biventricular physiology with systemic left ventricle
- For Part 1 PK/PD, patients must be treated with an ACEI (Angiotensin converting enzyme inhibitor) or ARB (Angiotensin receptor blockers) prior to screening.
For Part 1 PK/PD, patients in Group 1 and 2 must be currently treated with a daily dose equivalent of at least enalapril 0.2 mg/kg prior to the LCZ696 3.1 mg/kg single dose assessment.
For Part 1 PK/PD, patients in Group 3 must be currently treated with a daily dose equivalent of at least enalapril 0.1 mg/kg prior to the LCZ696
1.6 mg/kg single dose assessment
Sub-study entry criteria:
The patient is assigned at randomization in Part 2 of the main study CLCZ696B2319 to one of the following formulations:
LCZ696/ placebo liquid
OR
CZ696/ placebo granules
- Participant and/or participant's parent/caregiver capable of understanding the assessment procedures and participant obligations.
- Must not have any impairment in swallowing either solids or liquids as a consequence of acute or chronic illness and /or the inability to
participate in the palatability/acceptability assessment due to a condition that includes loss or alteration of taste.
Are the trial subjects under 18? yes
Number of subjects for this age range: 360
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
- 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
- For Part 2 only, 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
- For Part 2 only Active myocarditis
- Renal vascular hypertension (including renal artery stenosis)
- Moderate-to severe obstructive pulmonary disease
- Serum potassium >5.3 mmol/L at Visit 1 or at Visit 301
- History of angioedema
- Allergy or hypersensitivity to ACEI / ARB
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug
- Patient breastfed by a mother taking ACEI
Other protocol defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method