Pharmacokinetics, pharmacodynamics, safety and efficacy study of LCZ696 in children (1 month to < 18 years) with heart failure

Phase 1

• Conditions: Pediatric heart failure 1 month to <18 years old; MedDRA version: 20.0Level: LLTClassification code 10019279Term: Heart failureSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-004207-22-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-10-07
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

-Male or female, inpatient or outpatient, 1 month to < 18 years of age
- 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) any time prior
to screening
- 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

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
- 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