Phase 3
N=17
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
Pediatric Heart Failure
Bottom Line
View on ClinicalTrials.gov: NCT02678312 ↗Enrolled (actual)
17
Serious AEs
32.5%
Results posted
Feb 2023
Primary outcome: Primary: Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Maximum Drug Concentration in Plasma (Cmax) — 523; 179; 1970; 549 nanograms per milliliter (ng/ml)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- LCZ696 (Drug); Enalapril (Drug); Placebo of LCZ696 (Drug); Placebo of Enalapril (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Jan 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Maximum Drug Concentration in Plasma (Cmax) |
523; 179; 1970; 549; 124; 433 | — |
| PRIMARY Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Time to Maximum Plasma Concentration (Tmax) |
1.1; 1.2; 0.8; 1.2; 1.1; 1.0 | — |
| PRIMARY Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) |
690; 494; 3021; 1214; 270; 1063 | — |
| PRIMARY Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Number of Participants With Area Under the Plasma Concentration-time Curve From Time Zero to Last (AUClast) |
7; 8; 7; 6; 4; 5 | — |
| PRIMARY Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, and Valsartan): Clearance From Plasma (CL/F) |
0.73; 1.19; 0.63; 1.67; 1.19; 1.67 | — |
| PRIMARY Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril): Time Required to Drug Concentration to Decrease by Half (T 1/2) |
1.26; 1.53; 1.34; 1.51; 1.33 | — |
| PRIMARY Part 1: Pharmacodynamics (PD) of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Change From Baseline in Plasma B-type Natriuretic Peptide (BNP) |
100.87; 63.80; 97.52; 120.51; 21.20; 129.29 | — |
| PRIMARY Part 1: Pharmacodynamics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Change From Baseline in Plasma N-terminal Pro-brain Natriuretic Peptide (NTproBNP) |
2385.34; 2179.94; 961.76; 5086.37; 0.74; 0.59 | — |
| PRIMARY Part 1: Pharmacodynamics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Change From Baseline in Plasma Cyclic Guanosine Monophosphate (cGMP) |
18.18; 21.41; 12.20; 24.55; 13.38; 22.84 | — |
| PRIMARY Part 1: Pharmacodynamics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Change From Baseline in Urine cGMP |
1055.56; 1349.91; 914.57; 1123.69; 485.00; 386.32 | — |
| PRIMARY Part 2: Percentage of Participants With Worst Event in Each Category Based on Global Ranking |
10.16; 15.96; 9.63; 4.79; 6.95; 5.85 | — |
| SECONDARY Part 1: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) |
28.57; 50.00; 28.57; 50.00; 50.00; 80.00 | — |
| SECONDARY Part 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) |
88.77; 87.77 | — |
| SECONDARY Part 2: Exposure-adjusted Incidence Rate of Category 1 or Category 2 Event |
20.133; 20.042 | 0.7958 |
| SECONDARY Part 2: Percentage of Participants With Change From Baseline in New York Heart Association (NYHA)/Ross Functional Class |
14.21; 15.67; 84.15; 82.61; 1.64; 1.63 | — |
| SECONDARY Part 2: Percentage of Participants With Change From Baseline in Patient Global Impression of Severity (PGIS) Score |
27.01; 29.67; 58.05; 59.89; 14.94; 10.44 | — |
| SECONDARY Part 1 and Part 2: Population PK of LCZ696 Analytes: Clearance From Plasma (CL) |
25.93; 0.44; 1.97 | — |
| SECONDARY Part 1 and Part 2: Population PK of LCZ696 Analytes: Volume of Distribution in Steady State |
4.67; 0.34; 0.68 | — |
| SECONDARY Part 1 and Part 2: Population PK of LCZ696 Analytes: Absorption Rate Constant (Ka) |
1.25; 1.04; 1.42 | — |
| SECONDARY Part 1 and Part 2: Population PK of LCZ696 Analytes: Time Required to Drug Concentration to Decrease by Half (T 1/2) |
8.51; 18.21; 7.96 | — |
| SECONDARY Part 1 and Part 2: Population PK of LCZ696 Analytes: Maximum Drug Concentration in Plasma at Steady State (Cmax,ss) |
1348; 10153; 3861 | — |
| SECONDARY Part 1 and Part 2: Population PK of LCZ696 Analytes: Lowest Plasma Concentration Observed During a Dosing Interval at Steady State (Cmin,ss) |
63; 6442; 1442 | — |
| SECONDARY Part 1 and Part 2: Population PK of LCZ696 Analytes: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau at Steady State (AUCtau,ss) |
2179; 98906; 28672 | — |
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.
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 5.3 mmol/L
- History of angioedema
- Allergy or hypersensitivity to ACEI / ARB
Data sourced from ClinicalTrials.gov (NCT02678312). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.