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

Multicenter, open-label, study to evaluate safety, tolerability, pharmacokinetics and, pharmacodynamics of LCZ696 followed by a 52-week randomized, double-blind, parallel group, active-controlled study to evaluate the efficacy and safety of LCZ696 compared with enalapril in pediatric patients from1 month to < 18 years of age with heart failure due to systemic left ventricle systolic dysfunction

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-004207-22-FR

Enrollment

360

Registered

2017-03-01

Start date

Unknown

Completion date

Unknown

Last updated

2019-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pediatric heart failure 1 month to <18 years old MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849

Interventions

Product Name: LCZ696 12.5 mg film-coated granules in capsule (4 x 3.125 mg film-coated granules) Product Code: LCZ696 Pharmaceutical Form: Granules INN

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - 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 =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

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 at Visit 1 or at Visit 301 - History of angioedema - Allergy or hypersensitivity to ACEI / ARB Other protocol defined inclusion/exclusion criteria may apply.

Design outcomes

Primary

Measure	Time frame
Secondary Objective: Not applicable; Main Objective: This study consist of two parts (Part 1 and Part 2). Part 1: to evaluate the way the body absorbs, distributes and removes the drug LCZ696. This will help determine the proper dose of LCZ696 for Part 2 of the study. Part 2: to compare the effectiveness and safety of LCZ696 with enalapril in pediatric heart failure patients over 52 weeks of treatment. ; Primary end point(s): Part 1: - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Maximum drug concentration in plasma (Cmax). Cmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time to maximum plasma concentration (Tmax). Tmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): area under the plasma concentration-time curve from time zero to infinity (AUCinf) and area under the plasma concentration-time curve from time zero to last (AUClast). AUCinf and AUClast will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma (CL/F). CL/F will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half (T 1/2). T 1/2 will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods - Pharmacodynamics of LCZ696 analytes (sacubitril, LBQ657, and val	—

Measure

Time frame

Secondary Objective: Not applicable; Main Objective: This study consist of two parts (Part 1 and Part 2). Part 1: to evaluate the way the body absorbs, distributes and removes the drug LCZ696. This will help determine the proper dose of LCZ696 for Part 2 of the study. Part 2: to compare the effectiveness and safety of LCZ696 with enalapril in pediatric heart failure patients over 52 weeks of treatment. ; Primary end point(s): Part 1: - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Maximum drug concentration in plasma (Cmax). Cmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time to maximum plasma concentration (Tmax). Tmax will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): area under the plasma concentration-time curve from time zero to infinity (AUCinf) and area under the plasma concentration-time curve from time zero to last (AUClast). AUCinf and AUClast will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma (CL/F). CL/F will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods. - Pharmacokinetics of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half (T 1/2). T 1/2 will be determined for LCZ696 analytes (sacubitril, LBQ657, and valsartan) by using non-compartmental methods - Pharmacodynamics of LCZ696 analytes (sacubitril, LBQ657, and val

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Secondary

Measure	Time frame
Secondary end point(s): Part 1: To assess the safety and tolerability of LCZ696 in pediatric patients with heart failure Part 2: - Time to first occurrence of Category 1 or Category 2 event. Category 1: Death; United Network for Organ Sharing (UNOS) status 1A listing for heart transplant or equivalent; VAD/ECMO/mechanical ventilation/intra-aortic balloon pump requirement for life support at end of study. Category 2: Worsening HF (WHF); defined by signs and symptoms of WHF that requires an intensification of HF therapy - Change from baseline in NYHA/Ross functional class. NYHA/Ross functional class will be compared through 52 weeks of double-blind treatment - Change from baseline in Patient Global impression of severity score (PGIS) scale. PGIS scale will be compared for LCZ696 and enalapril through 52 weeks of double-blind treatment - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma in steady state (CL,ss). The steady state population PK parameter clearance will be estimated to be used in model. - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Volume of distribution in steady state. The steady state population PK parameter volume of distribution will be estimated to be used in model. - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Absorption rate constant in steady state (Ka,ss). The steady state population PK parameter Ka will be estimated to be used in model. - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half in steady state (T 1/2,ss). The steady state population PK parameter T 1/2 will be estimated to be used in model. - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Maximum drug concentration in plasma at s	—

Measure

Time frame

Secondary end point(s): Part 1: To assess the safety and tolerability of LCZ696 in pediatric patients with heart failure Part 2: - Time to first occurrence of Category 1 or Category 2 event. Category 1: Death; United Network for Organ Sharing (UNOS) status 1A listing for heart transplant or equivalent; VAD/ECMO/mechanical ventilation/intra-aortic balloon pump requirement for life support at end of study. Category 2: Worsening HF (WHF); defined by signs and symptoms of WHF that requires an intensification of HF therapy - Change from baseline in NYHA/Ross functional class. NYHA/Ross functional class will be compared through 52 weeks of double-blind treatment - Change from baseline in Patient Global impression of severity score (PGIS) scale. PGIS scale will be compared for LCZ696 and enalapril through 52 weeks of double-blind treatment - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Clearance from plasma in steady state (CL,ss). The steady state population PK parameter clearance will be estimated to be used in model. - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Volume of distribution in steady state. The steady state population PK parameter volume of distribution will be estimated to be used in model. - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Absorption rate constant in steady state (Ka,ss). The steady state population PK parameter Ka will be estimated to be used in model. - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Time required to drug concentration to decrease by half in steady state (T 1/2,ss). The steady state population PK parameter T 1/2 will be estimated to be used in model. - Population PK of LCZ696 analytes (sacubitril, LBQ657, and valsartan): Maximum drug concentration in plasma at s

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Countries

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Egypt, Finland, France, Germany, Hungary, India, Israel, Italy, Japan, Jordan, Korea, Republic of, Lebanon, Malaysia, Netherlands, Norway, Philippines, Poland, Portugal, Russian Federation, Saudi Arabia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Arab Emirates, United Kingdom, United States

Contacts

Public ContactInformation&Communication Médicales

Novartis Pharma S.A.S

icm.phfr@novartis.com+331 55476600

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026