Trial Outcomes & Findings for Efficacy and Safety of LCZ696 Compared to Placebo in Patients With Essential Hypertension (NCT NCT01193101)
NCT ID: NCT01193101
Last Updated: 2016-02-15
Results Overview
Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
389 participants
Primary outcome timeframe
Baseline, 8 weeks
Results posted on
2016-02-15
Participant Flow
This study comprised 3 periods: a 4 week washout and placebo run-in period, an 8 week randomized, double-blind period and a 1 week single-blind, placebo withdrawal period.
In the run-in period, 457 participants were enrolled. Of the 457 participants, 389 participants were eligible for randomization and randomized in a 1:1:1:1 ratio to each treatment group.
Participant milestones
| Measure |
LCZ696 100 mg
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
100
|
101
|
96
|
92
|
|
Overall Study
Full Analysis Set
|
100
|
101
|
96
|
92
|
|
Overall Study
Placebo Withdrawal Set
|
95
|
94
|
93
|
80
|
|
Overall Study
COMPLETED
|
95
|
94
|
93
|
80
|
|
Overall Study
NOT COMPLETED
|
5
|
7
|
3
|
12
|
Reasons for withdrawal
| Measure |
LCZ696 100 mg
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
1
|
3
|
|
Overall Study
Lack of Efficacy
|
3
|
1
|
0
|
8
|
|
Overall Study
Withdrawal by Subject
|
2
|
4
|
1
|
1
|
|
Overall Study
Administrative problems
|
0
|
0
|
1
|
0
|
|
Overall Study
Abnormal test procedure results
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Efficacy and Safety of LCZ696 Compared to Placebo in Patients With Essential Hypertension
Baseline characteristics by cohort
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=101 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
Total
n=389 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
52.5 Years
STANDARD_DEVIATION 10.03 • n=5 Participants
|
52.1 Years
STANDARD_DEVIATION 8.82 • n=7 Participants
|
50.9 Years
STANDARD_DEVIATION 9.81 • n=5 Participants
|
50.9 Years
STANDARD_DEVIATION 10.65 • n=4 Participants
|
51.6 Years
STANDARD_DEVIATION 9.82 • n=21 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
114 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
60 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
68 Participants
n=4 Participants
|
275 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, 8 weeksPopulation: Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.
Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=98 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
|
-11.53 mmHg
Standard Error 0.88
|
-10.98 mmHg
Standard Error 0.89
|
-12.45 mmHg
Standard Error 0.90
|
-3.69 mmHg
Standard Error 0.92
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.
Sitting BP measurements were performed at screening through the end of the study at every study visit. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=98 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
|
-16.83 mmHg
Standard Error 1.25
|
-17.54 mmHg
Standard Error 1.27
|
-20.35 mmHg
Standard Error 1.28
|
-4.97 mmHg
Standard Error 1.30
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.
Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
LCZ696 100 mg
n=81 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=84 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=82 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=73 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Change From Baseline in 24 Hour Mean Ambulatory DBP and SBP
maDBP
|
-8.34 mmHg
Standard Error 0.50
|
-9.33 mmHg
Standard Error 0.49
|
-9.69 mmHg
Standard Error 0.50
|
0.28 mmHg
Standard Error 0.52
|
|
Change From Baseline in 24 Hour Mean Ambulatory DBP and SBP
maSBP
|
-13.07 mmHg
Standard Error 0.65
|
-15.18 mmHg
Standard Error 0.64
|
-15.98 mmHg
Standard Error 0.65
|
0.19 mmHg
Standard Error 0.68
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.
Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Daytime mean SBP and DBP were the averages of the hourly means between 6 am and 10 pm. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
LCZ696 100 mg
n=81 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=84 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=82 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=73 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Change From Baseline in Daytime Mean Ambulatory DBP and SBP
maDBP
|
-8.46 mmHg
Standard Error 0.81
|
-8.65 mmHg
Standard Error 0.80
|
-9.77 mmHg
Standard Error 0.81
|
-0.13 mmHg
Standard Error 0.85
|
|
Change From Baseline in Daytime Mean Ambulatory DBP and SBP
maSBP
|
-13.29 mmHg
Standard Error 1.08
|
-14.62 mmHg
Standard Error 1.06
|
-16.58 mmHg
Standard Error 1.08
|
0.01 mmHg
Standard Error 1.13
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.
Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the average of the readings taken in the corresponding post-dosing hour at randomization and at week 8. Nighttime mean SBP and DBP were the averages of the hourly means between 10 pm and 6 am. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
LCZ696 100 mg
n=81 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=83 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=82 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=73 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Change From Baseline in Nighttime Mean Ambulatory DBP and SBP
maDBP
|
-7.96 mmHg
Standard Error 0.81
|
-10.36 mmHg
Standard Error 0.80
|
-9.47 mmHg
Standard Error 0.81
|
0.97 mmHg
Standard Error 0.85
|
|
Change From Baseline in Nighttime Mean Ambulatory DBP and SBP
maSBP
|
-12.27 mmHg
Standard Error 1.08
|
-16.14 mmHg
Standard Error 1.07
|
-14.65 mmHg
Standard Error 1.08
|
0.61 mmHg
Standard Error 1.13
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.
Mean sitting pulse pressure is the difference in msSBP and msDBP (msSBP - msDBP). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=98 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Pulse Pressure
|
-5.11 mmHg
Standard Error 0.81
|
-6.49 mmHg
Standard Error 0.83
|
-7.82 mmHg
Standard Error 0.83
|
-1.09 mmHg
Standard Error 0.85
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Participants from the full analysis set (FAS), who had both baseline and week 8 values, were analyzed. The FAS included all randomized participants.
Mean ambulatory pulse pressure is the difference in maSBP and maDBP (maSBP - maDBP). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
LCZ696 100 mg
n=81 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=84 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=82 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=73 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Change From Baseline in Mean Ambulatory Pulse Pressure
|
-4.68 mmHg
Standard Error 0.30
|
-5.84 mmHg
Standard Error 0.29
|
-6.31 mmHg
Standard Error 0.30
|
-0.08 mmHg
Standard Error 0.31
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Participants from the full analysis set (FAS), who had week 8 values, were analyzed. The FAS included all randomized participants.
Successful response in msDBP is defined as msDBP \<90 mmHg or a reduction ≥ 10 mmHg from baseline.
Outcome measures
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=98 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Number of Participants Who Achieved a Successful Response in msDBP
|
65 Participants
|
64 Participants
|
67 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Participants from the full analysis set (FAS), who had week 8 values, were analyzed. The FAS included all randomized participants.
Successful response in msSBP is defined as msSBP \<140 mmHg or a reduction ≥ 20 mmHg from baseline.
Outcome measures
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=98 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Number of Participants Who Achieved a Successful Response in msSBP
|
59 Participants
|
62 Participants
|
66 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Participants from the full analysis set (FAS), who had week 8 values, were analyzed. The FAS included all randomized participants.
BP control is defined as BP \< 140/90 mmHg.
Outcome measures
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=98 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Number of Participants Who Achieved Successful BP Control
|
47 Participants
|
48 Participants
|
52 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: baseline, 8 weeksPopulation: Full Analysis Set (FAS): The FAS included all randomized participants.
Trough to post-dosing hour ratio at each post-dosing hour = \[trough LSM of LCZ696 - trough LSM of placebo\]/\[post-dosing hour LSM of LCZ696 - post-dosing hour LSM of placebo\]
Outcome measures
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=98 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 11
|
0.82 ratio
|
1.31 ratio
|
1.19 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 6
|
0.73 ratio
|
1.04 ratio
|
1.21 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 7
|
0.68 ratio
|
1.00 ratio
|
1.03 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 8
|
0.75 ratio
|
0.88 ratio
|
0.99 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 9
|
0.80 ratio
|
1.07 ratio
|
1.01 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 10
|
0.76 ratio
|
1.15 ratio
|
1.11 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 1
|
0.95 ratio
|
1.32 ratio
|
1.28 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 2
|
0.76 ratio
|
1.03 ratio
|
0.90 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 3
|
0.64 ratio
|
1.35 ratio
|
0.91 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 4
|
0.77 ratio
|
1.30 ratio
|
1.18 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 5
|
0.82 ratio
|
1.18 ratio
|
1.05 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 12
|
0.56 ratio
|
0.92 ratio
|
0.89 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 13
|
0.67 ratio
|
0.86 ratio
|
0.88 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 14
|
0.69 ratio
|
0.91 ratio
|
0.85 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 15
|
0.57 ratio
|
0.69 ratio
|
0.74 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 16
|
0.58 ratio
|
0.65 ratio
|
0.80 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 17
|
0.89 ratio
|
0.92 ratio
|
1.02 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 18
|
0.86 ratio
|
0.92 ratio
|
1.07 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 19
|
0.83 ratio
|
0.99 ratio
|
1.13 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 20
|
0.84 ratio
|
1.06 ratio
|
1.18 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 21
|
0.76 ratio
|
1.02 ratio
|
1.02 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 22
|
0.98 ratio
|
1.09 ratio
|
0.80 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 23
|
1.02 ratio
|
0.93 ratio
|
0.81 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory DBP
Hour 24
|
1.00 ratio
|
1.00 ratio
|
1.00 ratio
|
—
|
SECONDARY outcome
Timeframe: baseline, 8 weeksPopulation: Full Analysis Set (FAS) The FAS included all randomized participants.
Trough to post-dosing hour ratio at each post-dosing hour = \[trough LSM of LCZ696 - trough LSM of placebo\]/\[post-dosing hour LSM of LCZ696 - post-dosing hour LSM of placebo\]
Outcome measures
| Measure |
LCZ696 100 mg
n=100 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=98 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 7
|
0.69 ratio
|
0.89 ratio
|
0.97 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 8
|
0.74 ratio
|
0.86 ratio
|
1.08 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 24
|
1.00 ratio
|
1.00 ratio
|
1.00 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 1
|
0.98 ratio
|
1.29 ratio
|
1.16 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 2
|
1.01 ratio
|
1.26 ratio
|
1.28 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 3
|
0.97 ratio
|
1.35 ratio
|
1.13 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 4
|
0.89 ratio
|
1.21 ratio
|
1.24 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 5
|
0.93 ratio
|
1.20 ratio
|
1.07 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 6
|
0.87 ratio
|
1.20 ratio
|
1.33 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 9
|
0.74 ratio
|
0.90 ratio
|
0.99 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 10
|
0.84 ratio
|
1.17 ratio
|
1.14 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 11
|
0.80 ratio
|
1.15 ratio
|
1.15 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 12
|
0.69 ratio
|
1.01 ratio
|
1.08 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 13
|
0.87 ratio
|
0.92 ratio
|
1.21 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 14
|
0.77 ratio
|
0.90 ratio
|
1.02 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 15
|
0.67 ratio
|
0.79 ratio
|
1.01 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 16
|
0.84 ratio
|
0.80 ratio
|
1.14 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 17
|
1.12 ratio
|
1.06 ratio
|
1.26 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 18
|
1.04 ratio
|
1.05 ratio
|
1.46 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 19
|
1.14 ratio
|
1.16 ratio
|
1.41 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 20
|
1.07 ratio
|
1.17 ratio
|
1.33 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 21
|
1.06 ratio
|
1.12 ratio
|
1.39 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 22
|
1.21 ratio
|
1.44 ratio
|
1.13 ratio
|
—
|
|
Trough to Post-dosing Hour Ratio for Change From Baseline in 24-hour Mean Ambulatory SBP
Hour 23
|
1.00 ratio
|
1.06 ratio
|
1.01 ratio
|
—
|
SECONDARY outcome
Timeframe: 8 weeks, 9 weeksPopulation: Only participants from the full analysis, who had values at both week 8 and week 9, were included in the analysis. The FAS included all randomized participants.
From week 8 to week 9, participants entered a single-blind placebo withdrawal period to assess the effect of LCZ696 on blood pressure following its discontinuation. Participants, who were randomized to the LCZ696 treatment groups, were discontinued from CLCZ696 at the end of week 8 and all 4 treatment groups received single-blind placebo for 1 week post week 8. A positive change from week 8 to week 9 indicates worsening.
Outcome measures
| Measure |
LCZ696 100 mg
n=95 Participants
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=94 Participants
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=93 Participants
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=80 Participants
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Change From Week 8 to Week 9 in msDBP and msSBP After Single-blind Placebo Withdrawal at Week 8
msDBP
|
4.8 mmHg
Standard Deviation 7.61
|
5.1 mmHg
Standard Deviation 7.03
|
5.6 mmHg
Standard Deviation 7.01
|
-0.6 mmHg
Standard Deviation 6.34
|
|
Change From Week 8 to Week 9 in msDBP and msSBP After Single-blind Placebo Withdrawal at Week 8
msSBP
|
8.0 mmHg
Standard Deviation 11.88
|
8.8 mmHg
Standard Deviation 11.62
|
11.6 mmHg
Standard Deviation 10.96
|
-0.7 mmHg
Standard Deviation 10.50
|
Adverse Events
LCZ696 100 mg
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
LCZ696 200 mg
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
LCZ696 400 mg
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LCZ696 100 mg
n=100 participants at risk
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=101 participants at risk
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 participants at risk
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 participants at risk
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
General disorders
Pyrexia
|
0.00%
0/100
|
0.00%
0/101
|
1.0%
1/96
|
0.00%
0/92
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/100
|
0.00%
0/101
|
1.0%
1/96
|
0.00%
0/92
|
|
Infections and infestations
Appendicitis
|
0.00%
0/100
|
0.99%
1/101
|
0.00%
0/96
|
0.00%
0/92
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/100
|
0.00%
0/101
|
1.0%
1/96
|
0.00%
0/92
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/100
|
0.00%
0/101
|
1.0%
1/96
|
0.00%
0/92
|
Other adverse events
| Measure |
LCZ696 100 mg
n=100 participants at risk
LCZ696 100 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 200 mg
n=101 participants at risk
LCZ696 200 mg plus placebo daily during double blind (DB) treatment for 8 weeks and then single-blind placebo for one week.
|
LCZ696 400 mg
n=96 participants at risk
LCZ696 200 mg LCZ696 plus placebo for one week, then titrated up to 400 mg plus placebo for the remaining 7 weeks during DB treatment, and then single-blind placebo for one week.
|
Placebo
n=92 participants at risk
Placebo daily for 8 weeks during DB treatment, and then single-blind placebo for 1 week.
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
6.0%
6/100
|
5.9%
6/101
|
7.3%
7/96
|
7.6%
7/92
|
|
Infections and infestations
Upper respiratory tract infection
|
9.0%
9/100
|
3.0%
3/101
|
4.2%
4/96
|
4.3%
4/92
|
|
Nervous system disorders
Dizziness
|
1.0%
1/100
|
2.0%
2/101
|
3.1%
3/96
|
5.4%
5/92
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: +1 (862) 778-1873
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER