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
CompletedPhase 2, PHASE3Results postedLast updated 10 February 2023
What this trial tests
Phase 2, PHASE3 trial testing LCZ696 in Pediatric Heart Failure in 393 participants. Completed in 3 January 2022.
Adults 1 Month to 17, any sex, with Pediatric Heart Failure. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Maximum Drug Concentration in Plasma (Cmax)Primary· Age group 1: Pre-dose and 0.5, 1, 2, 4, 8, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2; Age groups 2 and 3: Pre-dose and 1, 2, 4, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2
The analyses of Cmax was based on plasma concentrations of three sacubitril/valsartan analytes (AHU377 (sacubitril), LBQ657 (sacubitrilat), and valsartan). The plasma levels of sacubitril/valsartan analytes were determined using a validated LCMS/MS method with a lower limit of quantitation (LLOQ) of 1 ng/mL for sacubitril, 20 ng/mL for LBQ657, and 10 ng/mL for valsartan. The PK parameters were determined using the non-compartmental method(s).
Sacubitril
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
523
± 390
LCZ696: 0.8 mg/kg (Age Group 2)
179
± 97
LCZ696: 3.1 mg/kg (Age Group 1)
1970
± 1666
LCZ696: 3.1 mg/kg (Age Group 2)
549
± 298
LCZ696: 0.4 mg/kg (Age Group 3)
124
± 80
LCZ696: 1.6 mg/kg (Age Group 3)
433
± 181
LBQ657
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1951
± 839
LCZ696: 0.8 mg/kg (Age Group 2)
1359
± 711
LCZ696: 3.1 mg/kg (Age Group 1)
6707
± 1887
LCZ696: 3.1 mg/kg (Age Group 2)
5453
± 1032
LCZ696: 0.4 mg/kg (Age Group 3)
632
± 89
LCZ696: 1.6 mg/kg (Age Group 3)
2326
± 629
Valsartan
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1271
± 1011
LCZ696: 0.8 mg/kg (Age Group 2)
1112
± 583
LCZ696: 3.1 mg/kg (Age Group 1)
4035
± 1678
LCZ696: 3.1 mg/kg (Age Group 2)
4935
± 1268
LCZ696: 0.4 mg/kg (Age Group 3)
440
± 275
LCZ696: 1.6 mg/kg (Age Group 3)
2487
± 1564
Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Time to Maximum Plasma Concentration (Tmax)Primary· Age group 1: Pre-dose and 0.5, 1, 2, 4, 8, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2; Age groups 2 and 3: Pre-dose and 1, 2, 4, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2
The analyses of Tmax was based on plasma concentrations of three sacubitril/valsartan analytes (AHU377 (sacubitril), LBQ657 (sacubitrilat), and valsartan). The plasma levels of sacubitril/valsartan analytes were determined using a validated LCMS/MS method with a lower limit of quantitation (LLOQ) of 1 ng/mL for sacubitril, 20 ng/mL for LBQ657, and 10 ng/mL for valsartan. The PK parameters were determined using the non-compartmental method(s).
Sacubitril
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1.1
± 1.3
LCZ696: 0.8 mg/kg (Age Group 2)
1.2
± 0.5
LCZ696: 3.1 mg/kg (Age Group 1)
0.8
± 0.3
LCZ696: 3.1 mg/kg (Age Group 2)
1.2
± 0.4
LCZ696: 0.4 mg/kg (Age Group 3)
1.1
± 0.1
LCZ696: 1.6 mg/kg (Age Group 3)
1.0
± 0.0
LBQ657
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
4.0
± 2.0
LCZ696: 0.8 mg/kg (Age Group 2)
2.9
± 1.1
LCZ696: 3.1 mg/kg (Age Group 1)
2.9
± 1.1
LCZ696: 3.1 mg/kg (Age Group 2)
3.6
± 3.2
LCZ696: 0.4 mg/kg (Age Group 3)
2.8
± 1.6
LCZ696: 1.6 mg/kg (Age Group 3)
3.6
± 0.9
Valsartan
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1.7
± 1.1
LCZ696: 0.8 mg/kg (Age Group 2)
2.1
± 1.4
LCZ696: 3.1 mg/kg (Age Group 1)
2.6
± 1.0
LCZ696: 3.1 mg/kg (Age Group 2)
1.9
± 0.4
LCZ696: 0.4 mg/kg (Age Group 3)
1.8
± 1.5
LCZ696: 1.6 mg/kg (Age Group 3)
1.8
± 1.3
Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)Primary· Age group 1: Pre-dose and 0.5, 1, 2, 4, 8, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2; Age groups 2 and 3: Pre-dose and 1, 2, 4, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2
The analyses of AUCinf was based on plasma concentrations of three sacubitril/valsartan analytes (AHU377 (sacubitril), LBQ657 (sacubitrilat), and valsartan). The plasma levels of sacubitril/valsartan analytes were determined using a validated LCMS/MS method with a lower limit of quantitation (LLOQ) of 1 ng/mL for sacubitril, 20 ng/mL for LBQ657, and 10 ng/mL for valsartan. The PK parameters were determined using the non-compartmental method(s).
Sacubitril
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
690
± 410
LCZ696: 0.8 mg/kg (Age Group 2)
494
± 286
LCZ696: 3.1 mg/kg (Age Group 1)
3021
± 1814
LCZ696: 3.1 mg/kg (Age Group 2)
1214
± 684
LCZ696: 0.4 mg/kg (Age Group 3)
270
± 182
LCZ696: 1.6 mg/kg (Age Group 3)
1063
± 266
LBQ657
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
48264
± 22939
LCZ696: 0.8 mg/kg (Age Group 2)
31042
± 17259
LCZ696: 3.1 mg/kg (Age Group 1)
150440
± 49515
LCZ696: 3.1 mg/kg (Age Group 2)
127625
± 35634
LCZ696: 0.4 mg/kg (Age Group 3)
15835
± 2912
LCZ696: 1.6 mg/kg (Age Group 3)
62377
± 16035
Valsartan
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
13540
± 12962
LCZ696: 0.8 mg/kg (Age Group 2)
11036
± 7031
LCZ696: 3.1 mg/kg (Age Group 1)
40733
± 21003
LCZ696: 3.1 mg/kg (Age Group 2)
48561
± 21163
LCZ696: 0.4 mg/kg (Age Group 3)
3923
± 1424
LCZ696: 1.6 mg/kg (Age Group 3)
26170
± 16826
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)Primary· Age group 1: Pre-dose and 0.5, 1, 2, 4, 8, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2; Age groups 2 and 3: Pre-dose and 1, 2, 4, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2
As prespecified in protocol and SAP the analysis of this outcome measure was done based on dose of LCZ696 administered within the different age groups.
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
7
LCZ696: 0.8 mg/kg (Age Group 2)
8
LCZ696: 3.1 mg/kg (Age Group 1)
7
LCZ696: 3.1 mg/kg (Age Group 2)
6
LCZ696: 0.4 mg/kg (Age Group 3)
4
LCZ696: 1.6 mg/kg (Age Group 3)
5
Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril, and Valsartan): Clearance From Plasma (CL/F)Primary· Age group 1: Pre-dose and 0.5, 1, 2, 4, 8, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2; Age groups 2 and 3: Pre-dose and 1, 2, 4, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2
The analyses was based on plasma concentrations of two sacubitril/valsartan analytes (AHU377 (sacubitril), and valsartan). The plasma levels of sacubitril/valsartan analytes were determined using a validated LCMS/MS method with a lower limit of quantitation (LLOQ) of 1 ng/mL for sacubitril, 20 ng/mL for LBQ657, and 10 ng/mL for valsartan. The PK parameters were determined using the non-compartmental method(s). CL/F was not estimated for LBQ657 as it is a metabolite.
Sacubitril
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
0.73
± 0.35
LCZ696: 0.8 mg/kg (Age Group 2)
1.19
± 0.96
LCZ696: 3.1 mg/kg (Age Group 1)
0.63
± 0.28
LCZ696: 3.1 mg/kg (Age Group 2)
1.67
± 1.01
LCZ696: 0.4 mg/kg (Age Group 3)
1.19
± 1.11
LCZ696: 1.6 mg/kg (Age Group 3)
1.67
± 1.01
Valsartan
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
0.06
± 0.05
LCZ696: 0.8 mg/kg (Age Group 2)
0.07
± 0.09
LCZ696: 3.1 mg/kg (Age Group 1)
0.06
± 0.06
LCZ696: 3.1 mg/kg (Age Group 2)
0.04
± 0.01
LCZ696: 0.4 mg/kg (Age Group 3)
0.06
± 0.02
LCZ696: 1.6 mg/kg (Age Group 3)
0.05
± 0.03
Part 1: Pharmacokinetics of LCZ696 Analytes (Sacubitril): Time Required to Drug Concentration to Decrease by Half (T 1/2)Primary· Age group 1: Pre-dose and 0.5, 1, 2, 4, 8, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2; Age groups 2 and 3: Pre-dose and 1, 2, 4, 10, optional 24 hours post-dose on Day 1 of Period 1 and 2
The analyses of T1/2 was based on plasma concentrations of sacubitril. The plasma levels of sacubitril/valsartan analytes were determined using a validated LCMS/MS method with a lower limit of quantitation (LLOQ) of 1 ng/mL for sacubitril, 20 ng/mL for LBQ657, and 10 ng/mL for valsartan. The PK parameters were determined using the non-compartmental method(s). T1/2 for other analytes of LCZ696 (LBQ657 and Valsartan) was not estimable due to the short sample collection timeframe.
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1.26
0.95 – 2.36
LCZ696: 0.8 mg/kg (Age Group 2)
1.53
1.40 – 1.65
LCZ696: 3.1 mg/kg (Age Group 1)
1.34
1.16 – 1.60
LCZ696: 3.1 mg/kg (Age Group 2)
1.51
1.34 – 1.70
LCZ696: 1.6 mg/kg (Age Group 3)
1.33
1.16 – 1.64
Part 1: Pharmacodynamics (PD) of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Change From Baseline in Plasma B-type Natriuretic Peptide (BNP)Primary· Baseline (0 hrs pre dose), 4 and 8 hrs post dose on Day 1 of Period 1 and Period 2
Biomarkers were used to assess the PD effects of LCZ696. Blood biomarkers of potential interest included plasma BNP. Biomarkers related to heart failure or the mechanism of action of the study drug were measured. Summary statistics for change from baseline at each time point is presented. The baseline assessment is defined as the last non-missing assessment (scheduled or unscheduled) prior to (the first dose time of the study drug within the dose associated period). For each post-dose time point, participants are included if and only if the participant has both pre-dose assessment and current
Baseline (0 hrs pre dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
100.87
49.84 – 204.13
LCZ696: 0.8 mg/kg (Age Group 2)
63.80
8.65 – 470.81
LCZ696: 3.1 mg/kg (Age Group 1)
97.52
51.59 – 184.32
LCZ696: 3.1 mg/kg (Age Group 2)
120.51
5.21 – 2787.44
LCZ696: 0.4 mg/kg (Age Group 3)
21.20
2.14 – 210.41
LCZ696: 1.6 mg/kg (Age Group 3)
129.29
9.45 – 1768.43
Change From Baseline (4 hrs post dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1.31
0.93 – 1.85
LCZ696: 0.8 mg/kg (Age Group 2)
1.60
0.21 – 11.95
LCZ696: 3.1 mg/kg (Age Group 1)
1.22
0.94 – 1.58
LCZ696: 3.1 mg/kg (Age Group 2)
0.62
NA – NA
LCZ696: 0.4 mg/kg (Age Group 3)
0.77
0.56 – 1.05
LCZ696: 1.6 mg/kg (Age Group 3)
1.09
0.61 – 1.93
Change From Baseline (8 hrs post dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1.32
0.92 – 1.88
LCZ696: 0.8 mg/kg (Age Group 2)
1.21
0.21 – 7.04
LCZ696: 3.1 mg/kg (Age Group 1)
0.97
0.70 – 1.34
LCZ696: 3.1 mg/kg (Age Group 2)
0.80
NA – NA
LCZ696: 0.4 mg/kg (Age Group 3)
0.59
0.27 – 1.30
LCZ696: 1.6 mg/kg (Age Group 3)
0.55
0.15 – 2.02
Part 1: Pharmacodynamics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Change From Baseline in Plasma N-terminal Pro-brain Natriuretic Peptide (NTproBNP)Primary· Baseline (0 hrs pre dose) and optional 24 hrs post dosing on Day 1 of Period 1 and Period 2
Biomarkers were used to assess the PD effects of LCZ696. Blood biomarkers of potential interest included plasma NTproBNP. Biomarkers related to heart failure or the mechanism of action of the study drug were measured. Summary statistics for change from baseline at each time point is presented. The baseline assessment is defined as the last non-missing assessment (scheduled or unscheduled) prior to (the first dose time of the study drug within the dose associated period). For each post-dose time point, participants are included if and only if the participant has both pre-dose assessment and cur
Baseline (0 hrs pre dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
2385.34
1186.13 – 4796.98
LCZ696: 3.1 mg/kg (Age Group 1)
2179.94
932.77 – 5094.69
LCZ696: 0.4 mg/kg (Age Group 3)
961.76
125.65 – 7361.70
LCZ696: 1.6 mg/kg (Age Group 3)
5086.37
683.53 – 37849.47
Change From Baseline (24 hrs post dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
0.74
0.31 – 1.78
LCZ696: 0.4 mg/kg (Age Group 3)
0.59
0.00 – 134.25
LCZ696: 1.6 mg/kg (Age Group 3)
0.41
0.34 – 0.48
Part 1: Pharmacodynamics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Change From Baseline in Plasma Cyclic Guanosine Monophosphate (cGMP)Primary· Baseline (0 hrs pre dose), 4 and 8 hrs post dose on Day 1 of Period 1 and Period 2
Biomarkers were used to assess the PD effects of LCZ696. Blood biomarkers of potential interest included plasma cGMP. Biomarkers related to heart failure or the mechanism of action of the study drug were measured. Summary statistics for change from baseline at each time point is presented. The baseline assessment is defined as the last non-missing assessment (scheduled or unscheduled) prior to (the first dose time of the study drug within the dose associated period). For each post-dose time point, participants are included if and only if the participant has both pre-dose assessment and current
Baseline (0 hrs pre dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
18.18
12.01 – 27.51
LCZ696: 0.8 mg/kg (Age Group 2)
21.41
12.83 – 35.71
LCZ696: 3.1 mg/kg (Age Group 1)
12.20
8.13 – 18.32
LCZ696: 3.1 mg/kg (Age Group 2)
24.55
18.37 – 32.82
LCZ696: 0.4 mg/kg (Age Group 3)
13.38
0.05 – 3883.59
LCZ696: 1.6 mg/kg (Age Group 3)
22.84
12.51 – 41.68
Change From Baseline (4 hrs post dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1.30
0.89 – 1.90
LCZ696: 0.8 mg/kg (Age Group 2)
0.90
0.50 – 1.62
LCZ696: 3.1 mg/kg (Age Group 1)
1.54
1.12 – 2.10
LCZ696: 3.1 mg/kg (Age Group 2)
1.02
0.52 – 2.01
LCZ696: 0.4 mg/kg (Age Group 3)
0.80
0.00 – 618.02
LCZ696: 1.6 mg/kg (Age Group 3)
0.78
0.27 – 2.22
Change From Baseline (8 hrs post dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1.17
0.91 – 1.50
LCZ696: 0.8 mg/kg (Age Group 2)
0.92
0.66 – 1.29
LCZ696: 3.1 mg/kg (Age Group 1)
1.60
1.10 – 2.31
LCZ696: 3.1 mg/kg (Age Group 2)
0.40
0.02 – 8.86
LCZ696: 0.4 mg/kg (Age Group 3)
0.79
0.00 – 230.10
LCZ696: 1.6 mg/kg (Age Group 3)
0.79
0.29 – 2.18
Part 1: Pharmacodynamics of LCZ696 Analytes (Sacubitril, LBQ657, and Valsartan): Change From Baseline in Urine cGMPPrimary· Baseline (0 hrs pre dose), 4 to 8 hrs post dose on Day 1 of Period 1 and Period 2
Biomarkers were used to assess the PD effects of LCZ696. Blood biomarkers of potential interest included urine cGMP. Biomarkers related to heart failure or the mechanism of action of the study drug were measured. Summary statistics for change from baseline at each time point is presented. The baseline assessment is defined as the last non-missing assessment (scheduled or unscheduled) prior to (the first dose time of the study drug within the dose associated period). For each post-dose time point, participants are included if and only if the participant has both pre-dose assessment and current
Baseline (0 hrs pre dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1055.56
352.98 – 3156.55
LCZ696: 0.8 mg/kg (Age Group 2)
1349.91
118.48 – 15380.33
LCZ696: 3.1 mg/kg (Age Group 1)
914.57
311.65 – 2683.88
LCZ696: 3.1 mg/kg (Age Group 2)
1123.69
75.21 – 16789.03
LCZ696: 0.4 mg/kg (Age Group 3)
485.00
NA – NA
LCZ696: 1.6 mg/kg (Age Group 3)
386.32
134.04 – 1113.42
Change From Baseline (4 to 8 hrs post dose)
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
1.42
0.38 – 5.32
LCZ696: 0.8 mg/kg (Age Group 2)
0.80
0.02 – 27.03
LCZ696: 3.1 mg/kg (Age Group 1)
1.79
0.65 – 4.96
LCZ696: 3.1 mg/kg (Age Group 2)
2.17
0.10 – 45.16
LCZ696: 0.4 mg/kg (Age Group 3)
0.92
0.02 – 51.75
LCZ696: 1.6 mg/kg (Age Group 3)
1.98
0.51 – 7.63
Part 2: Percentage of Participants With Worst Event in Each Category Based on Global RankingPrimary· Up to 52 weeks
Global ranking is based on 5 categories ranking worst to best outcome:Category 1:Death; United Network for Organ Sharing(UNOS)status 1A listing for heart transplant or equivalent; ventricular assist device(VAD)/extracorporeal membrane oxygenation(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. Category 3:Worsened; worse New York Heart Association(NYHA)/Ross or worse Patient Global Impression of Severity(PGIS); and further ranking
Category 1
Group
Value
95% CI
Part 2: LCZ696
10.16
Part 2: Enalapril
15.96
Category 2
Group
Value
95% CI
Part 2: LCZ696
9.63
Part 2: Enalapril
4.79
Category 3
Group
Value
95% CI
Part 2: LCZ696
6.95
Part 2: Enalapril
5.85
Category 4
Group
Value
95% CI
Part 2: LCZ696
20.86
Part 2: Enalapril
26.60
Category 5
Group
Value
95% CI
Part 2: LCZ696
39.57
Part 2: Enalapril
35.64
Missing
Group
Value
95% CI
Part 2: LCZ696
12.83
Part 2: Enalapril
11.17
Part 1: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)Secondary· From first dose to 30 days after last dose of study drug in Part 1
An adverse event (AE) is any untoward medical occurrence associated with use of a drug in humans, whether considered drug related or not, that occurs after a participant provides informed consent. TEAEs during part 1 are defined as any recorded AE with its start date (recorded or imputed) later than or equal to the date of the first dose of the study drug within part 1 and its start date prior to or equal to the end date of the part 1.
Group
Value
95% CI
LCZ696: 0.8 mg/kg (Age Group 1)
28.57
LCZ696: 0.8 mg/kg (Age Group 2)
50.00
LCZ696: 3.1 mg/kg (Age Group 1)
28.57
LCZ696: 3.1 mg/kg (Age Group 2)
50.00
LCZ696: 0.4 mg/kg (Age Group 3)
50.00
LCZ696: 1.6 mg/kg (Age Group 3)
80.00
Part 1: Dose Cohort S
50.00
Adverse events — posted to ClinicalTrials.gov
Time frame: Adverse events were collected from first dose of study treatment plus 30 days post treatment up to approximately one year..
Reporting threshold: 1%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Part 1: Dose Cohort 1
Serious: 2/17 (12%)
Deaths: 0/17
Part 1: Dose Cohort 2
Serious: 1/18 (6%)
Deaths: 0/18
Part 1: Dose Cohort S
Serious: 0/2 (0%)
Deaths: 0/2
Part 2: LCZ696
Serious: 69/187 (37%)
Deaths: 8/187
Part 2: Enalapril
Serious: 62/188 (33%)
Deaths: 12/188
Serious adverse events (128 terms)
Reaction
System
Part 1: Dose Cohort 1
Part 1: Dose Cohort 2
Part 1: Dose Cohort S
Part 2: LCZ696
Part 2: Enalapril
Cardiac failure
Cardiac disorders
—
—
—
—
—
Vomiting
Gastrointestinal disorders
—
—
—
—
—
Pneumonia
Infections and infestations
—
—
—
—
—
Cardiac arrest
Cardiac disorders
—
—
—
—
—
Cardiac failure acute
Cardiac disorders
—
—
—
—
—
Cardiac failure congestive
Cardiac disorders
—
—
—
—
—
Pyrexia
General disorders
—
—
—
—
—
Upper respiratory tract infection
Infections and infestations
—
—
—
—
—
Seizure
Nervous system disorders
—
—
—
—
—
Hypotension
Vascular disorders
—
—
—
—
—
Arrhythmia
Cardiac disorders
—
—
—
—
—
Ventricular tachycardia
Cardiac disorders
—
—
—
—
—
Dyspnoea
Respiratory, thoracic and mediastinal disorders
—
—
—
—
—
Atrial thrombosis
Cardiac disorders
—
—
—
—
—
Chest pain
General disorders
—
—
—
—
—
Bronchiolitis
Infections and infestations
—
—
—
—
—
Influenza
Infections and infestations
—
—
—
—
—
Viral upper respiratory tract infection
Infections and infestations
—
—
—
—
—
Dehydration
Metabolism and nutrition disorders
—
—
—
—
—
Hyperkalaemia
Metabolism and nutrition disorders
—
—
—
—
—
Hypoglycaemia
Metabolism and nutrition disorders
—
—
—
—
—
Syncope
Nervous system disorders
—
—
—
—
—
Acute kidney injury
Renal and urinary disorders
—
—
—
—
—
Acute respiratory failure
Respiratory, thoracic and mediastinal disorders
—
—
—
—
—
Pleural effusion
Respiratory, thoracic and mediastinal disorders
—
—
—
—
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Other adverse events (147 terms — click to expand)
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.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT04164732 — Study of Efficacy of Oral Sacubitril/Valsartan in Adult Patients With Non-obstructive Hypertrophic Cardiomyopathy
· Phase 2
· completed
NCT03872778 — [177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-neoB Lesion Uptake
· Phase 1, PHASE2
· completed
NCT03909295 — An Open-label Extension Study Evaluating Safety and Tolerability of LCZ696 in Subjects Who Completed PARAGON-HF in Japan
· Phase 3
· terminated
NCT03917459 — COmparing arNi and Ace For Improving Erectile Dysfunction in mEN With reduCed Ejection Fraction Heart Failure
· Phase 3
· completed
NCT07498335 — Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary
· Phase 3
· not yet recruiting
NCT07489573 — Study of Efficacy and Safety of Secukinumab in Chinese Adult Patients With Moderate to Severe Hidradenitis Suppurativa
· Phase 4
· not yet recruiting
NCT07484269 — PULSE Registry: for Patients Receiving Lutetium (177Lu) Vipivotide Tetraxetan
· not yet recruiting
NCT07416162 — A Study of Iptacopan in Korean Patients With Paroxysmal Nocturnal Hemoglobinuria or C3 Glomerulopathy
· not yet recruiting
NCT07387926 — Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+
· Phase 1, PHASE2
· not yet recruiting
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Novartis Pharmaceuticals
Last refreshed: 10 February 2023
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02678312.