Trial Outcomes & Findings for Efficacy and Safety of LCZ696A in Patients With Essential Hypertension (NCT NCT00549770)
NCT ID: NCT00549770
Last Updated: 2015-08-25
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
1334 participants
Primary outcome timeframe
baseline, week 8
Results posted on
2015-08-25
Participant Flow
The study comprised 3 periods: a 4-week washout and placebo run-in period (pre-randomization), an 8-week randomized, double-blind monotherapy period, and 1-week randomized, placebo-controlled withdrawal period. In the randomized withdrawal, participants were either randomized to placebo or continued their original assigned treatment.
After successful completion of the pre-randomization period, participants were randomized 1:1:1:1:1:1:1:1 ratio to one of 8 treatment groups.
Participant milestones
| Measure |
LCZ696 100 mg
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
156
|
169
|
172
|
163
|
166
|
164
|
165
|
173
|
|
Overall Study
Intent-to-treat Population
|
154
|
168
|
170
|
163
|
163
|
163
|
164
|
172
|
|
Overall Study
Ambulatory Blood Pressure Monitoring
|
48
|
61
|
53
|
55
|
49
|
54
|
50
|
57
|
|
Overall Study
COMPLETED
|
149
|
158
|
162
|
147
|
149
|
151
|
151
|
148
|
|
Overall Study
NOT COMPLETED
|
7
|
11
|
10
|
16
|
17
|
13
|
14
|
25
|
Reasons for withdrawal
| Measure |
LCZ696 100 mg
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
Protocol deviation
|
1
|
1
|
1
|
2
|
2
|
2
|
1
|
2
|
|
Overall Study
Administrative problems
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
2
|
2
|
3
|
2
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
4
|
6
|
4
|
5
|
6
|
6
|
4
|
9
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
2
|
3
|
5
|
1
|
3
|
8
|
|
Overall Study
Abnormal test procedure results
|
0
|
0
|
0
|
2
|
0
|
1
|
1
|
1
|
|
Overall Study
Abnormal laboratory values
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Adverse Event
|
1
|
3
|
1
|
2
|
1
|
0
|
5
|
4
|
Baseline Characteristics
Efficacy and Safety of LCZ696A in Patients With Essential Hypertension
Baseline characteristics by cohort
| Measure |
LCZ696 100 mg
n=156 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=169 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=172 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=166 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=164 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=165 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=173 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Total
n=1328 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
53 years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
54 years
STANDARD_DEVIATION 9.7 • n=7 Participants
|
52 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
53 years
STANDARD_DEVIATION 9.6 • n=4 Participants
|
53 years
STANDARD_DEVIATION 9.7 • n=21 Participants
|
53 years
STANDARD_DEVIATION 10.1 • n=8 Participants
|
53 years
STANDARD_DEVIATION 10.7 • n=8 Participants
|
54 years
STANDARD_DEVIATION 10.6 • n=24 Participants
|
53 years
STANDARD_DEVIATION 10.2 • n=42 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
68 Participants
n=4 Participants
|
68 Participants
n=21 Participants
|
65 Participants
n=8 Participants
|
75 Participants
n=8 Participants
|
79 Participants
n=24 Participants
|
568 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
95 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
97 Participants
n=5 Participants
|
95 Participants
n=4 Participants
|
98 Participants
n=21 Participants
|
99 Participants
n=8 Participants
|
90 Participants
n=8 Participants
|
94 Participants
n=24 Participants
|
760 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: baseline, week 8Population: Intent-to-treat (ITT): The ITT included all randomized participants who had a baseline and at least one post-baseline efficacy measuremet during the 8-week core treatment period.
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=154 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=168 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=170 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=163 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=163 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=164 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=172 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
|
-9.97 mmHg
Standard Error 0.73
|
-12.92 mmHg
Standard Error 0.70
|
-13.63 mmHg
Standard Error 0.70
|
-9.14 mmHg
Standard Error 0.72
|
-9.95 mmHg
Standard Error 0.71
|
-10.93 mmHg
Standard Error 0.71
|
-9.76 mmHg
Standard Error 0.71
|
-6.78 mmHg
Standard Error 0.69
|
SECONDARY outcome
Timeframe: baseline, week 8Population: Intent-to-treat (ITT): The ITT included all randomized participants who had a baseline and at least one post-baseline efficacy measuremet during the 8-week core treatment period.
Sitting BP measurements were performed at screening through the end of the study at every study visit.
Outcome measures
| Measure |
LCZ696 100 mg
n=154 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=168 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=170 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=163 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=163 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=164 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=172 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
|
-13.75 mmHg
Standard Error 1.15
|
-18.70 mmHg
Standard Error 1.10
|
-20.17 mmHg
Standard Error 1.10
|
-12.44 mmHg
Standard Error 1.12
|
-13.42 mmHg
Standard Error 1.12
|
-14.16 mmHg
Standard Error 1.12
|
-11.93 mmHg
Standard Error 1.11
|
-7.72 mmHg
Standard Error 1.09
|
SECONDARY outcome
Timeframe: baseline, 8 weeksPopulation: Ambulatory Blood Pressure Monitoring (ABPM) Subset: The ABPM subest included all ITT participants who had both baseline and week 8 ABPM values.
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.
Outcome measures
| Measure |
LCZ696 100 mg
n=48 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=61 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=53 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=55 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=49 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=54 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=50 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=57 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP
maDBP
|
-3.80 mmHg
Standard Error 0.72
|
-6.78 mmHg
Standard Error 0.64
|
-8.32 mmHg
Standard Error 0.71
|
-4.56 mmHg
Standard Error 0.67
|
-6.25 mmHg
Standard Error 0.70
|
-7.13 mmHg
Standard Error 0.67
|
-3.67 mmHg
Standard Error 0.70
|
-1.33 mmHg
Standard Error 0.67
|
|
Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP
maSBP
|
-7.80 mmHg
Standard Error 1.04
|
-11.50 mmHg
Standard Error 0.93
|
-14.56 mmHg
Standard Error 1.03
|
-7.29 mmHg
Standard Error 0.96
|
-8.27 mmHg
Standard Error 1.00
|
-9.42 mmHg
Standard Error 0.97
|
-5.18 mmHg
Standard Error 1.02
|
-2.90 mmHg
Standard Error 0.96
|
SECONDARY outcome
Timeframe: baseline, 8 weeksPopulation: Ambulatory Blood Pressure Monitoring (ABPM) Subset: The ABPM subest included all ITT participants who had both baseline and week 8 ABPM values.
Hourly mean ambulatory DBP and SBP post-dosing was calculated for each post-dosing hour over 24 hours by taking the avergae 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.
Outcome measures
| Measure |
LCZ696 100 mg
n=48 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=61 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=53 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=55 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=49 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=54 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=50 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=57 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Daytime maDBP and maSBP
maDBP
|
-4.05 mmHg
Standard Error 1.23
|
-6.91 mmHg
Standard Error 1.12
|
-7.80 mmHg
Standard Error 1.19
|
-4.78 mmHg
Standard Error 1.17
|
-7.40 mmHg
Standard Error 1.23
|
-7.47 mmHg
Standard Error 1.17
|
-3.18 mmHg
Standard Error 1.22
|
-1.53 mmHg
Standard Error 1.14
|
|
Change From Baseline in Daytime maDBP and maSBP
maSBP
|
-7.96 mmHg
Standard Error 1.73
|
-11.76 mmHg
Standard Error 1.58
|
-14.20 mmHg
Standard Error 1.67
|
-7.59 mmHg
Standard Error 1.65
|
-9.54 mmHg
Standard Error 1.73
|
-9.90 mmHg
Standard Error 1.66
|
-4.49 mmHg
Standard Error 1.72
|
-3.40 mmHg
Standard Error 1.61
|
SECONDARY outcome
Timeframe: baseline, 8 weeksPopulation: Participants from the ABPM subset, who had both baseline nighttime and week 8 nighttime values, were included in the analysis only.
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.
Outcome measures
| Measure |
LCZ696 100 mg
n=45 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=59 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=47 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=54 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=48 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=53 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=47 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=55 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Nighttime maDBP and maSBP
maDBP
|
-2.87 mmHg
Standard Error 1.25
|
-7.73 mmHg
Standard Error 1.13
|
-6.93 mmHg
Standard Error 1.23
|
-4.04 mmHg
Standard Error 1.17
|
-4.18 mmHg
Standard Error 1.24
|
-6.17 mmHg
Standard Error 1.18
|
-3.31 mmHg
Standard Error 1.24
|
-1.01 mmHg
Standard Error 1.16
|
|
Change From Baseline in Nighttime maDBP and maSBP
maSBP
|
-6.40 mmHg
Standard Error 1.77
|
-11.85 mmHg
Standard Error 1.60
|
-12.04 mmHg
Standard Error 1.73
|
-6.43 mmHg
Standard Error 1.66
|
-5.82 mmHg
Standard Error 1.74
|
-7.51 mmHg
Standard Error 1.67
|
-3.99 mmHg
Standard Error 1.75
|
-2.09 mmHg
Standard Error 1.63
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Intent-to-treat (ITT): The ITT included all randomized participants who had a baseline and at least one post-baseline efficacy measuremet during the 8-week core treatment period.
Successful response in msDBP is defined as msDBP \<90 mmHg or a reduction ≥ 10 mmHg from baseline.
Outcome measures
| Measure |
LCZ696 100 mg
n=154 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=168 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=170 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=163 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=163 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=164 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=172 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved a Successful Response in msDBP
|
53.90 Percentage of participants
|
69.64 Percentage of participants
|
74.12 Percentage of participants
|
51.53 Percentage of participants
|
55.83 Percentage of participants
|
63.19 Percentage of participants
|
54.27 Percentage of participants
|
39.53 Percentage of participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Intent-to-treat (ITT): The ITT included all randomized participants who had a baseline and at least one post-baseline efficacy measuremet during the 8-week core treatment period.
Successful response in msSBP is defined as msSBP \<140 mmHg or a reduction ≥ 20 mmHg from baseline.
Outcome measures
| Measure |
LCZ696 100 mg
n=154 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=168 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=170 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=163 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=163 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=164 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=172 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved a Successful Response in msSBP
|
55.84 Percentage of participants
|
63.69 Percentage of participants
|
72.35 Percentage of participants
|
51.53 Percentage of participants
|
51.53 Percentage of participants
|
57.06 Percentage of participants
|
46.34 Percentage of participants
|
37.79 Percentage of participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Intent-to-treat (ITT): The ITT included all randomized participants who had a baseline and at least one post-baseline efficacy measuremet during the 8-week core treatment period.
Successful control in msDBP is defined as msDBP \<90 mmHg.
Outcome measures
| Measure |
LCZ696 100 mg
n=154 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=168 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=170 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=163 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=163 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=164 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=172 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved Successful Control in msDBP
|
47.40 Percentage of participants
|
60.12 Percentage of participants
|
65.88 Percentage of participants
|
45.40 Percentage of participants
|
47.85 Percentage of participants
|
56.44 Percentage of participants
|
46.95 Percentage of participants
|
38.37 Percentage of participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Intent-to-treat (ITT): The ITT included all randomized participants who had a baseline and at least one post-baseline efficacy measuremet during the 8-week core treatment period.
Successful control in msSBP is defined as \<140 mmHg.
Outcome measures
| Measure |
LCZ696 100 mg
n=154 Participants
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=168 Participants
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=170 Participants
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 Participants
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=163 Participants
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=163 Participants
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=164 Participants
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=172 Participants
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Percentage of Participants Who Achieved Successful Control in msSBP
|
47.40 Percentage of participants
|
56.55 Percentage of participants
|
62.94 Percentage of participants
|
45.40 Percentage of participants
|
42.33 Percentage of participants
|
53.37 Percentage of participants
|
37.20 Percentage of participants
|
31.98 Percentage of participants
|
Adverse Events
LCZ696 100 mg
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
LCZ696 200 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
LCZ696 400 mg
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Valsartan 80 mg
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Valsartan 160 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Valsartan 320 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
AHU377 200 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LCZ696 100 mg
n=156 participants at risk
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=169 participants at risk
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=172 participants at risk
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 participants at risk
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=166 participants at risk
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=164 participants at risk
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=165 participants at risk
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=173 participants at risk
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.64%
1/156
|
0.00%
0/169
|
0.00%
0/172
|
0.00%
0/163
|
0.00%
0/166
|
0.00%
0/164
|
0.00%
0/165
|
0.00%
0/173
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.64%
1/156
|
0.00%
0/169
|
0.00%
0/172
|
0.00%
0/163
|
0.00%
0/166
|
0.00%
0/164
|
0.00%
0/165
|
0.00%
0/173
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/156
|
0.00%
0/169
|
0.58%
1/172
|
0.00%
0/163
|
0.00%
0/166
|
0.00%
0/164
|
0.00%
0/165
|
0.00%
0/173
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.00%
0/156
|
0.00%
0/169
|
0.00%
0/172
|
0.61%
1/163
|
0.00%
0/166
|
0.00%
0/164
|
0.00%
0/165
|
0.00%
0/173
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/156
|
0.00%
0/169
|
0.58%
1/172
|
0.00%
0/163
|
0.00%
0/166
|
0.00%
0/164
|
0.00%
0/165
|
0.00%
0/173
|
Other adverse events
| Measure |
LCZ696 100 mg
n=156 participants at risk
Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 200 mg
n=169 participants at risk
Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
LCZ696 400 mg
n=172 participants at risk
Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 80 mg
n=163 participants at risk
Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 160 mg
n=166 participants at risk
Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
Valsartan 320 mg
n=164 participants at risk
Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
AHU377 200 mg
n=165 participants at risk
Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
|
Placebo
n=173 participants at risk
Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
|
|---|---|---|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
2.6%
4/156
|
2.4%
4/169
|
2.3%
4/172
|
3.1%
5/163
|
2.4%
4/166
|
1.8%
3/164
|
3.0%
5/165
|
7.5%
13/173
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER