Trial Outcomes & Findings for An 8-week Study to Evaluate the Dose Response of AHU377 in Combination With Valsartan 320 mg in Patients With Mild-to-moderate Systolic Hypertension (NCT NCT01281306)
NCT ID: NCT01281306
Last Updated: 2016-01-29
Results Overview
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
910 participants
Primary outcome timeframe
Baseline, 8 weeks
Results posted on
2016-01-29
Participant Flow
This study consisted of a single-blind run-in period and a double-blind (DB) period. During the 3 to 4 week run-in, participants were assessed for randomization eligibility into the DB period. 910 participants randomized. 3 participants were mis-randomized and did not receive study treatment. Therefore, the participant flow shows 907 participants.
In the double blind period, participants were randomized in a 2:2:2:2:2:2:1 ratio to AHU377 400 mg + valsartan 320 mg, AHU377 200 mg + valsartan 320 mg, AHU377 100 mg + valsartan 320 mg, AHU377 50 mg + valsartan 320 mg,valsartan 320 mg, LCZ696 400 mg and placebo, respectively.
Participant milestones
| Measure |
VAL + AHU 400 mg
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
144
|
145
|
141
|
134
|
143
|
142
|
58
|
|
Overall Study
Full Analysis Set
|
143
|
145
|
141
|
133
|
143
|
142
|
58
|
|
Overall Study
Safety Set
|
143
|
145
|
141
|
133
|
143
|
142
|
58
|
|
Overall Study
Ambulatory Blood Pressure Monitoring Set
|
95
|
99
|
92
|
95
|
93
|
91
|
35
|
|
Overall Study
COMPLETED
|
136
|
141
|
133
|
123
|
134
|
135
|
51
|
|
Overall Study
NOT COMPLETED
|
8
|
4
|
8
|
11
|
9
|
7
|
7
|
Reasons for withdrawal
| Measure |
VAL + AHU 400 mg
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
3
|
0
|
2
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
2
|
4
|
1
|
3
|
1
|
|
Overall Study
Protocol deviation
|
0
|
1
|
1
|
1
|
1
|
0
|
0
|
|
Overall Study
Condition no longer requires study drug
|
1
|
0
|
0
|
0
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
2
|
0
|
0
|
1
|
|
Overall Study
Death
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Adverse Event
|
3
|
2
|
2
|
3
|
5
|
3
|
3
|
|
Overall Study
Randomized in error
|
1
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
An 8-week Study to Evaluate the Dose Response of AHU377 in Combination With Valsartan 320 mg in Patients With Mild-to-moderate Systolic Hypertension
Baseline characteristics by cohort
| Measure |
VAL + AHU 400 mg
n=144 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=145 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=141 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=134 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=143 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=142 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=58 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
Total
n=907 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
61.7 Years
STANDARD_DEVIATION 11.36 • n=5 Participants
|
61.7 Years
STANDARD_DEVIATION 11.44 • n=7 Participants
|
61.0 Years
STANDARD_DEVIATION 11.03 • n=5 Participants
|
62.0 Years
STANDARD_DEVIATION 10.73 • n=4 Participants
|
62.0 Years
STANDARD_DEVIATION 11.45 • n=21 Participants
|
61.2 Years
STANDARD_DEVIATION 10.60 • n=10 Participants
|
60.8 Years
STANDARD_DEVIATION 11.81 • n=115 Participants
|
61.5 Years
STANDARD_DEVIATION 11.13 • n=24 Participants
|
|
Sex: Female, Male
Female
|
78 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
60 Participants
n=21 Participants
|
71 Participants
n=10 Participants
|
29 Participants
n=115 Participants
|
412 Participants
n=24 Participants
|
|
Sex: Female, Male
Male
|
66 Participants
n=5 Participants
|
85 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
73 Participants
n=4 Participants
|
83 Participants
n=21 Participants
|
71 Participants
n=10 Participants
|
29 Participants
n=115 Participants
|
495 Participants
n=24 Participants
|
PRIMARY outcome
Timeframe: Baseline, 8 weeksPopulation: Only participants of the full analysuis set (FAS), who had measurements at both baseline and week 8, were included in the analysis. The FAS included all randomized participants who received at least one dose of double-blind study medication.
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=143 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=144 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=141 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=132 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=143 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=142 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=57 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
|
-20.89 mmHg
Standard Error 1.22
|
-23.55 mmHg
Standard Error 1.21
|
-21.26 mmHg
Standard Error 1.23
|
-19.31 mmHg
Standard Error 1.27
|
-16.13 mmHg
Standard Error 1.22
|
-21.78 mmHg
Standard Error 1.22
|
-6.99 mmHg
Standard Error 1.92
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Only participants of the full analysuis set (FAS), who had measurements at both baseline and week 8, were included in the analysis. The FAS included all randomized participants who received at least one dose of double-blind study medication.
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=143 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=144 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=141 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=132 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=143 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=142 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=57 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Diastolic Blood Pressure (msDBP)
|
-8.47 mmHg
Standard Error 0.76
|
-9.76 mmHg
Standard Error 0.75
|
-8.04 mmHg
Standard Error 0.76
|
-7.15 mmHg
Standard Error 0.79
|
-7.28 mmHg
Standard Error 0.76
|
-9.61 mmHg
Standard Error 0.75
|
-3.38 mmHg
Standard Error 1.19
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=94 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=98 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=92 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=95 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=93 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=90 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=35 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP)
maSBP
|
-12.14 mmHg
Standard Error 0.71
|
-15.66 mmHg
Standard Error 0.69
|
-14.33 mmHg
Standard Error 0.72
|
-11.36 mmHg
Standard Error 0.70
|
-9.59 mmHg
Standard Error 0.71
|
-12.98 mmHg
Standard Error 0.71
|
-2.12 mmHg
Standard Error 1.15
|
|
Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP)
maDBP
|
-5.81 mmHg
Standard Error 0.44
|
-7.03 mmHg
Standard Error 0.42
|
-6.46 mmHg
Standard Error 0.44
|
-5.36 mmHg
Standard Error 0.43
|
-5.23 mmHg
Standard Error 0.44
|
-6.20 mmHg
Standard Error 0.44
|
-0.79 mmHg
Standard Error 0.71
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Twenty four hour ABPM was performed twice during the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=94 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=98 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=92 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=95 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=93 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=90 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=35 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Daytime maSBP and maDBP
maSBP
|
-12.62 mmHg
Standard Error 1.21
|
-15.85 mmHg
Standard Error 1.19
|
-14.43 mmHg
Standard Error 1.23
|
-11.50 mmHg
Standard Error 1.21
|
-9.60 mmHg
Standard Error 1.22
|
-13.32 mmHg
Standard Error 1.23
|
-2.39 mmHg
Standard Error 1.98
|
|
Change From Baseline in Daytime maSBP and maDBP
maDBP
|
-5.93 mmHg
Standard Error 0.77
|
-7.13 mmHg
Standard Error 0.75
|
-6.57 mmHg
Standard Error 0.78
|
-5.39 mmHg
Standard Error 0.77
|
-5.40 mmHg
Standard Error 0.77
|
-6.16 mmHg
Standard Error 0.78
|
-0.98 mmHg
Standard Error 1.26
|
SECONDARY outcome
Timeframe: Baseline and 8 weeksPopulation: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=91 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=98 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=90 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=95 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=92 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=90 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=35 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Nighttime maSBP and maDBP
maDBP
|
-5.27 mmHg
Standard Error 0.78
|
-6.79 mmHg
Standard Error 0.75
|
-6.45 mmHg
Standard Error 0.78
|
-5.27 mmHg
Standard Error 0.77
|
-4.49 mmHg
Standard Error 0.77
|
-6.36 mmHg
Standard Error 0.78
|
-0.22 mmHg
Standard Error 1.26
|
|
Change From Baseline in Nighttime maSBP and maDBP
maSBP
|
-11.57 mmHg
Standard Error 1.23
|
-15.27 mmHg
Standard Error 1.19
|
-14.74 mmHg
Standard Error 1.23
|
-10.80 mmHg
Standard Error 1.21
|
-8.88 mmHg
Standard Error 1.22
|
-12.34 mmHg
Standard Error 1.23
|
-1.36 mmHg
Standard Error 1.98
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Only participants of the full analysis set (FAS), who had measurements at both baseline and week 8, were included in the analysis. The FAS included all randomized participants who received at least one dose of double-blind study medication.
Pulse rate measurements were performed. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=143 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=144 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=141 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=132 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=143 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=142 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=57 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Sitting Pulse Pressure
|
-12.39 mmHg
Standard Error 0.91
|
-13.91 mmHg
Standard Error 0.90
|
-13.18 mmHg
Standard Error 0.91
|
-12.01 mmHg
Standard Error 0.95
|
-8.80 mmHg
Standard Error 0.91
|
-12.18 mmHg
Standard Error 0.91
|
-3.74 mmHg
Standard Error 1.43
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Pulse rate measurements were performed. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=94 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=98 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=92 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=95 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=93 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=90 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=35 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Ambulatory Pulse Pressure
|
-6.23 mmHg
Standard Error 0.39
|
-8.51 mmHg
Standard Error 0.38
|
-7.71 mmHg
Standard Error 0.40
|
-6.00 mmHg
Standard Error 0.39
|
-4.40 mmHg
Standard Error 0.39
|
-6.84 mmHg
Standard Error 0.39
|
-1.09 mmHg
Standard Error 0.63
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Twenty four hour ABPM was performed twice during the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=32 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=42 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=38 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=42 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=38 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=37 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=19 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in maSBP and maDBP in Dippers
maSBP
|
-11.43 mmHg
Standard Error 1.12
|
-15.59 mmHg
Standard Error 1.00
|
-12.04 mmHg
Standard Error 1.05
|
10.60 mmHg
Standard Error 1.01
|
-9.85 mmHg
Standard Error 1.03
|
-13.09 mmHg
Standard Error 1.05
|
-2.39 mmHg
Standard Error 1.45
|
|
Change From Baseline in maSBP and maDBP in Dippers
maDBP
|
-4.62 mmHg
Standard Error 0.70
|
-7.33 mmHg
Standard Error 0.62
|
-5.49 mmHg
Standard Error 0.65
|
-5.07 mmHg
Standard Error 0.63
|
-5.53 mmHg
Standard Error 0.64
|
-6.03 mmHg
Standard Error 0.65
|
-0.98 mmHg
Standard Error 0.90
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. Dippers were defined as participants who showed a decrease of at least 10% in maSBP during the night (10pm-6am) compared with the daytime level. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=59 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=56 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=53 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=53 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=54 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=53 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=16 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in maSBP and maDBP in Non-dippers
maDBP
|
-6.65 mmHg
Standard Error 0.56
|
-6.91 mmHg
Standard Error 0.58
|
-7.31 mmHg
Standard Error 0.60
|
-5.79 mmHg
Standard Error 0.61
|
-5.10 mmHg
Standard Error 0.59
|
-6.34 mmHg
Standard Error 0.59
|
-0.49 mmHg
Standard Error 1.08
|
|
Change From Baseline in maSBP and maDBP in Non-dippers
maSBP
|
-12.81 mmHg
Standard Error 0.91
|
-16.08 mmHg
Standard Error 0.94
|
-16.37 mmHg
Standard Error 0.97
|
-12.17 mmHg
Standard Error 0.99
|
-9.73 mmHg
Standard Error 0.96
|
-13.12 mmHg
Standard Error 0.96
|
-1.46 mmHg
Standard Error 1.75
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Only participants of the full analysuis set (FAS), who were \< 65 years of age and had measurements at both baseline and week 8, were included in the analysis. The FAS included all randomized participants who received at least one dose of double-blind study medication.
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=75 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=75 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=78 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=66 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=73 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=79 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=28 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age
msSBP
|
-20.95 mmHg
Standard Error 1.68
|
-24.45 mmHg
Standard Error 1.67
|
-20.94 mmHg
Standard Error 1.63
|
-18.09 mmHg
Standard Error 1.79
|
-16.96 mmHg
Standard Error 1.71
|
-21.06 mmHg
Standard Error 1.63
|
-8.94 mmHg
Standard Error 2.73
|
|
Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age
msDBP
|
-8.97 mmHg
Standard Error 1.11
|
-10.94 mmHg
Standard Error 1.11
|
-8.83 mmHg
Standard Error 1.09
|
-8.07 mmHg
Standard Error 1.19
|
-6.93 mmHg
Standard Error 1.13
|
-10.25 mmHg
Standard Error 1.08
|
-5.19 mmHg
Standard Error 1.82
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: Only participants of the full analysuis set (FAS), who were \>= 65 years of age and had measurements at both baseline and week 8, were included in the analysis. The FAS included all randomized participants who received at least one dose of double-blind study medication.
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=68 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=69 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=63 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=66 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=70 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=63 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=29 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age
msSBP
|
-20.93 mmHg
Standard Error 1.79
|
-22.66 mmHg
Standard Error 1.76
|
-21.72 mmHg
Standard Error 1.85
|
-20.64 mmHg
Standard Error 1.81
|
-15.48 mmHg
Standard Error 1.75
|
-22.83 mmHg
Standard Error 1.84
|
-5.10 mmHg
Standard Error 2.71
|
|
Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age
msDBP
|
-7.89 mmHg
Standard Error 1.02
|
-8.44 mmHg
Standard Error 1.00
|
-7.06 mmHg
Standard Error 1.05
|
-6.17 mmHg
Standard Error 1.03
|
-7.62 mmHg
Standard Error 0.99
|
-8.89 mmHg
Standard Error 1.04
|
-1.46 mmHg
Standard Error 1.54
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: A subset of randomized participants, who were leass than 65 years of age and had ABPM measurements at both baseline and week 8, were included in the analysis.
Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=44 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=50 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=46 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=47 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=44 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=48 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=15 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age
maSBP
|
-12.16 mmHg
Standard Error 0.98
|
-15.06 mmHg
Standard Error 0.91
|
-14.42 mmHg
Standard Error 0.95
|
-10.39 mmHg
Standard Error 0.95
|
-9.55 mmHg
Standard Error 0.99
|
-13.98 mmHg
Standard Error 0.93
|
-2.24 mmHg
Standard Error 1.67
|
|
Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age
maDBP
|
-6.74 mmHg
Standard Error 0.67
|
-7.81 mmHg
Standard Error 0.62
|
-7.93 mmHg
Standard Error 0.65
|
-5.69 mmHg
Standard Error 0.65
|
-5.94 mmHg
Standard Error 0.67
|
-7.32 mmHg
Standard Error 0.63
|
-1.53 mmHg
Standard Error 1.14
|
SECONDARY outcome
Timeframe: Baseline, 8 weeksPopulation: A subset of randomized participants, who were \>= 65 years of age and had ABPM measurements at both baseline and week 8, were included in the analysis.
Twenty four hour ABPM was performed twice duirng the study at baseline and week 8. The second ABPM assessment was performed only in participants who had successfully completed the ABPM assessment at baseline. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=50 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=48 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=46 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=48 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=49 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=42 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=20 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age
maSBP
|
-12.10 mmHg
Standard Error 1.04
|
-16.08 mmHg
Standard Error 1.03
|
-14.20 mmHg
Standard Error 1.08
|
-12.25 mmHg
Standard Error 1.04
|
-9.73 mmHg
Standard Error 1.02
|
-11.88 mmHg
Standard Error 1.10
|
-1.95 mmHg
Standard Error 1.59
|
|
Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age
maDBP
|
-4.94 mmHg
Standard Error 0.58
|
-6.00 mmHg
Standard Error 0.57
|
-4.86 mmHg
Standard Error 0.60
|
-4.93 mmHg
Standard Error 0.58
|
-4.58 mmHg
Standard Error 0.56
|
-5.04 mmHg
Standard Error 0.61
|
-0.01 mmHg
Standard Error 0.88
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Only participants of the full analysuis set (FAS), who had week 8 measurements, were included in the analysis. The FAS included all randomized participants who received at least one dose of double-blind study medication.
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). Blood pressure control was defined as msSBP/MSDBP \< 140/90 mmHg. Blood pressure response in msSBP was defined as \<140 mmHg or a reduction \>= 20mmHg from baseline. Blood pressure response in msDBP was defined as \< 90 mmHg or a reduction \>= 10 mmHg from baseline.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=143 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=144 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=141 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=132 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=143 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=142 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=57 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response
Blood pressure control
|
72 Number of participants
|
86 Number of participants
|
71 Number of participants
|
58 Number of participants
|
57 Number of participants
|
76 Number of participants
|
8 Number of participants
|
|
Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response
msSBP response
|
88 Number of participants
|
101 Number of participants
|
93 Number of participants
|
81 Number of participants
|
72 Number of participants
|
94 Number of participants
|
11 Number of participants
|
|
Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response
msDBP response
|
112 Number of participants
|
126 Number of participants
|
114 Number of participants
|
101 Number of participants
|
111 Number of participants
|
118 Number of participants
|
39 Number of participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Safety Analysis Set: The safety analysis set included all randomized participants who received at least one dose of study medication.
Adverse event monitoring was conducted throughout the study.
Outcome measures
| Measure |
VAL + AHU 400 mg
n=143 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=145 Participants
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=141 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=133 Participants
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=143 Participants
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=142 Participants
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=58 Participants
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death
Adverse events (non-serious and serious)
|
40 Number of participants
|
31 Number of participants
|
29 Number of participants
|
25 Number of participants
|
38 Number of participants
|
42 Number of participants
|
20 Number of participants
|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death
Serious adverse events
|
3 Number of participants
|
1 Number of participants
|
1 Number of participants
|
0 Number of participants
|
1 Number of participants
|
1 Number of participants
|
1 Number of participants
|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death
Deaths
|
1 Number of participants
|
0 Number of participants
|
0 Number of participants
|
0 Number of participants
|
0 Number of participants
|
0 Number of participants
|
0 Number of participants
|
Adverse Events
VAL + AHU 400 mg
Serious events: 3 serious events
Other events: 1 other events
Deaths: 0 deaths
VAL + AHU 200 mg
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
VAL + AHU 100 mg
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
VAL + AHU 50 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
VAL 320 mg
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
LCZ 400 mg
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
VAL + AHU 400 mg
n=143 participants at risk
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=145 participants at risk
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=141 participants at risk
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=133 participants at risk
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=143 participants at risk
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=142 participants at risk
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=58 participants at risk
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
General disorders
Sudden death
|
0.70%
1/143
|
0.00%
0/145
|
0.00%
0/141
|
0.00%
0/133
|
0.00%
0/143
|
0.00%
0/142
|
0.00%
0/58
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.70%
1/143
|
0.00%
0/145
|
0.00%
0/141
|
0.00%
0/133
|
0.00%
0/143
|
0.00%
0/142
|
0.00%
0/58
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/143
|
0.00%
0/145
|
0.71%
1/141
|
0.00%
0/133
|
0.00%
0/143
|
0.00%
0/142
|
0.00%
0/58
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/143
|
0.00%
0/145
|
0.00%
0/141
|
0.00%
0/133
|
0.70%
1/143
|
0.00%
0/142
|
0.00%
0/58
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/143
|
0.00%
0/145
|
0.00%
0/141
|
0.00%
0/133
|
0.00%
0/143
|
0.70%
1/142
|
0.00%
0/58
|
|
Psychiatric disorders
Schizophrenia
|
0.00%
0/143
|
0.69%
1/145
|
0.00%
0/141
|
0.00%
0/133
|
0.00%
0/143
|
0.00%
0/142
|
0.00%
0/58
|
|
Renal and urinary disorders
Calculus urinary
|
0.00%
0/143
|
0.00%
0/145
|
0.00%
0/141
|
0.00%
0/133
|
0.00%
0/143
|
0.00%
0/142
|
1.7%
1/58
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.70%
1/143
|
0.00%
0/145
|
0.00%
0/141
|
0.00%
0/133
|
0.00%
0/143
|
0.00%
0/142
|
0.00%
0/58
|
Other adverse events
| Measure |
VAL + AHU 400 mg
n=143 participants at risk
Participants were started with AHU377 100 mg + valsartan 160 mg every day (qd) for 1 week, then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for another week, and then were uptitrated to AHU377 400 mg + valsartan 320 mg for the remaining 6 weeks.
|
VAL + AHU 200 mg
n=145 participants at risk
Participants were started with AHU377 100 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 200 mg + valsartan 320 mg qd for the remaining 7 weeks.
|
VAL + AHU 100 mg
n=141 participants at risk
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 100 mg + valsartan 320 mg for the remaining 7 weeks.
|
VAL + AHU 50 mg
n=133 participants at risk
Participants were started with AHU377 50 mg + valsartan 160 mg qd for 1 week and then were uptitrated to AHU377 50 mg + valartan 320 mg qd for the remaining 7 weeks.
|
VAL 320 mg
n=143 participants at risk
Participants were started with valsartan 160 mg qd for 1 week and then were uptitrated to valsartan 320 mg qd for the remaining 7 weeks.
|
LCZ 400 mg
n=142 participants at risk
Participants were started with LCZ696 200 mg qd for 1 week and then were uptitrated to LCZ696 400 mg qd for the remaining 7 weeks.
|
Placebo
n=58 participants at risk
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
|
|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Dyspepsia
|
0.70%
1/143
|
1.4%
2/145
|
0.71%
1/141
|
1.5%
2/133
|
2.8%
4/143
|
0.70%
1/142
|
5.2%
3/58
|
Additional Information
Study Director
Novartis
Phone: 862-778-8300
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