Systolic Hypertension
Conditions
Keywords
hypertension, blood pressure, LCZ696, dual-acting, neprilysin, nep inhibitor, vasopeptidase, angiotensin receptor, angiotensin receptor neprilysin inhibitor (ARNi)
Brief summary
The purpose of the study is to evaluate dose response of blood pressure lowering for 4 doses of AHU377, given once daily (50 mg, 100 mg, 200 mg and 400 mg) in combination with a fixed dose of valsartan (320 mg).
Interventions
DRUGLCZ696
LCZ696 was supplied as tablets in blister cards in 100 mg strengths.
DRUGValsartan
Valsartan was supplied as tablets in blister cards in 160 mg and 320 mg strengths.
DRUGAHU377
AHU377 was supplied in tablets in blister cards in 50 mg and 100 mg strengths.
DRUGPlacebo
Placebo was supplied as tablets in blister cards.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained before any assessment is performed. Patients with mild-to-moderate systolic hypertension, untreated or currently taking antihypertensive therapy. * Ability to communicate and comply with all study requirements and demonstrate good medication compliance (≥ 80% compliance rate) during the run-in period.
Exclusion criteria
* Severe hypertension * History of angioedema, drug-related or otherwise, as reported by the patient. * Pregnant or nursing (lactating) women. * Women of child-bearing potential (WOCBP), UNLESS they are using adequate birth control methods. * History or evidence of a secondary form of hypertension. * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | Baseline, 8 weeks | Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | Baseline, 8 weeks | 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. |
| Change From Baseline in Daytime maSBP and maDBP | Baseline, 8 weeks | 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. |
| Change From Baseline in Nighttime maSBP and maDBP | Baseline and 8 weeks | 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. |
| Change From Baseline in Mean Sitting Pulse Pressure | Baseline, 8 weeks | Pulse rate measurements were performed. A negative change from baseline indicates improvement. |
| Change From Baseline in Mean Ambulatory Pulse Pressure | Baseline, 8 weeks | Pulse rate measurements were performed. A negative change from baseline indicates improvement. |
| Change From Baseline in maSBP and maDBP in Dippers | Baseline, 8 weeks | 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. |
| Change From Baseline in Mean Diastolic Blood Pressure (msDBP) | Baseline, 8 weeks | Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement. |
| Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | Baseline, 8 weeks | Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement. |
| Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | Baseline, 8 weeks | Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement. |
| Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | Baseline, 8 weeks | 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. |
| Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | Baseline, 8 weeks | 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. |
| Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | 8 weeks | 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. |
| Number of Participants With Adverse Events, Serious Adverse Events and Death | 8 weeks | Adverse event monitoring was conducted throughout the study. |
| Change From Baseline in maSBP and maDBP in Non-dippers | Baseline, 8 weeks | 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. |
Countries
Argentina, Canada, Hungary, India, Romania, Slovakia, South Korea, Spain, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 144 |
| 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. | 145 |
| 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. | 141 |
| 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. | 134 |
| 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. | 143 |
| 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. | 142 |
| Placebo Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks. | 58 |
| Total | 907 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 2 | 3 | 5 | 3 | 3 |
| Overall Study | Condition no longer requires study drug | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 | 3 | 0 | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 2 | 0 | 0 | 1 |
| Overall Study | Protocol deviation | 0 | 1 | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Randomized in error | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 | 4 | 1 | 3 | 1 |
Baseline characteristics
| Characteristic | VAL + AHU 400 mg | VAL + AHU 200 mg | VAL + AHU 100 mg | VAL + AHU 50 mg | VAL 320 mg | LCZ 400 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 61.7 Years STANDARD_DEVIATION 11.36 | 61.7 Years STANDARD_DEVIATION 11.44 | 61.0 Years STANDARD_DEVIATION 11.03 | 62.0 Years STANDARD_DEVIATION 10.73 | 62.0 Years STANDARD_DEVIATION 11.45 | 61.2 Years STANDARD_DEVIATION 10.6 | 60.8 Years STANDARD_DEVIATION 11.81 | 61.5 Years STANDARD_DEVIATION 11.13 |
| Sex: Female, Male Female | 78 Participants | 60 Participants | 53 Participants | 61 Participants | 60 Participants | 71 Participants | 29 Participants | 412 Participants |
| Sex: Female, Male Male | 66 Participants | 85 Participants | 88 Participants | 73 Participants | 83 Participants | 71 Participants | 29 Participants | 495 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 143 | 2 / 145 | 1 / 141 | 2 / 133 | 4 / 143 | 1 / 142 | 3 / 58 |
| serious Total, serious adverse events | 3 / 143 | 1 / 145 | 1 / 141 | 0 / 133 | 1 / 143 | 1 / 142 | 1 / 58 |
Outcome results
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Time frame: Baseline, 8 weeks
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -20.89 mmHg | Standard Error 1.22 |
| VAL + AHU 200 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -23.55 mmHg | Standard Error 1.21 |
| VAL + AHU 100 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -21.26 mmHg | Standard Error 1.23 |
| VAL + AHU 50 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -19.31 mmHg | Standard Error 1.27 |
| VAL 320 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -16.13 mmHg | Standard Error 1.22 |
| LCZ 400 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -21.78 mmHg | Standard Error 1.22 |
| Placebo | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) | -6.99 mmHg | Standard Error 1.92 |
Secondary
Change From Baseline in Daytime maSBP and maDBP
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.
Time frame: Baseline, 8 weeks
Population: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in Daytime maSBP and maDBP | maSBP | -12.62 mmHg | Standard Error 1.21 |
| VAL + AHU 400 mg | Change From Baseline in Daytime maSBP and maDBP | maDBP | -5.93 mmHg | Standard Error 0.77 |
| VAL + AHU 200 mg | Change From Baseline in Daytime maSBP and maDBP | maSBP | -15.85 mmHg | Standard Error 1.19 |
| VAL + AHU 200 mg | Change From Baseline in Daytime maSBP and maDBP | maDBP | -7.13 mmHg | Standard Error 0.75 |
| VAL + AHU 100 mg | Change From Baseline in Daytime maSBP and maDBP | maSBP | -14.43 mmHg | Standard Error 1.23 |
| VAL + AHU 100 mg | Change From Baseline in Daytime maSBP and maDBP | maDBP | -6.57 mmHg | Standard Error 0.78 |
| VAL + AHU 50 mg | Change From Baseline in Daytime maSBP and maDBP | maSBP | -11.50 mmHg | Standard Error 1.21 |
| VAL + AHU 50 mg | Change From Baseline in Daytime maSBP and maDBP | maDBP | -5.39 mmHg | Standard Error 0.77 |
| VAL 320 mg | Change From Baseline in Daytime maSBP and maDBP | maSBP | -9.60 mmHg | Standard Error 1.22 |
| VAL 320 mg | Change From Baseline in Daytime maSBP and maDBP | maDBP | -5.40 mmHg | Standard Error 0.77 |
| LCZ 400 mg | Change From Baseline in Daytime maSBP and maDBP | maSBP | -13.32 mmHg | Standard Error 1.23 |
| LCZ 400 mg | Change From Baseline in Daytime maSBP and maDBP | maDBP | -6.16 mmHg | Standard Error 0.78 |
| Placebo | Change From Baseline in Daytime maSBP and maDBP | maSBP | -2.39 mmHg | Standard Error 1.98 |
| Placebo | Change From Baseline in Daytime maSBP and maDBP | maDBP | -0.98 mmHg | Standard Error 1.26 |
Secondary
Change From Baseline in maSBP and maDBP in Dippers
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.
Time frame: Baseline, 8 weeks
Population: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in maSBP and maDBP in Dippers | maSBP | -11.43 mmHg | Standard Error 1.12 |
| VAL + AHU 400 mg | Change From Baseline in maSBP and maDBP in Dippers | maDBP | -4.62 mmHg | Standard Error 0.7 |
| VAL + AHU 200 mg | Change From Baseline in maSBP and maDBP in Dippers | maSBP | -15.59 mmHg | Standard Error 1 |
| VAL + AHU 200 mg | Change From Baseline in maSBP and maDBP in Dippers | maDBP | -7.33 mmHg | Standard Error 0.62 |
| VAL + AHU 100 mg | Change From Baseline in maSBP and maDBP in Dippers | maSBP | -12.04 mmHg | Standard Error 1.05 |
| VAL + AHU 100 mg | Change From Baseline in maSBP and maDBP in Dippers | maDBP | -5.49 mmHg | Standard Error 0.65 |
| VAL + AHU 50 mg | Change From Baseline in maSBP and maDBP in Dippers | maSBP | 10.60 mmHg | Standard Error 1.01 |
| VAL + AHU 50 mg | Change From Baseline in maSBP and maDBP in Dippers | maDBP | -5.07 mmHg | Standard Error 0.63 |
| VAL 320 mg | Change From Baseline in maSBP and maDBP in Dippers | maSBP | -9.85 mmHg | Standard Error 1.03 |
| VAL 320 mg | Change From Baseline in maSBP and maDBP in Dippers | maDBP | -5.53 mmHg | Standard Error 0.64 |
| LCZ 400 mg | Change From Baseline in maSBP and maDBP in Dippers | maSBP | -13.09 mmHg | Standard Error 1.05 |
| LCZ 400 mg | Change From Baseline in maSBP and maDBP in Dippers | maDBP | -6.03 mmHg | Standard Error 0.65 |
| Placebo | Change From Baseline in maSBP and maDBP in Dippers | maSBP | -2.39 mmHg | Standard Error 1.45 |
| Placebo | Change From Baseline in maSBP and maDBP in Dippers | maDBP | -0.98 mmHg | Standard Error 0.9 |
Secondary
Change From Baseline in maSBP and maDBP in Non-dippers
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.
Time frame: Baseline, 8 weeks
Population: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maDBP | -6.65 mmHg | Standard Error 0.56 |
| VAL + AHU 400 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maSBP | -12.81 mmHg | Standard Error 0.91 |
| VAL + AHU 200 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maSBP | -16.08 mmHg | Standard Error 0.94 |
| VAL + AHU 200 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maDBP | -6.91 mmHg | Standard Error 0.58 |
| VAL + AHU 100 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maSBP | -16.37 mmHg | Standard Error 0.97 |
| VAL + AHU 100 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maDBP | -7.31 mmHg | Standard Error 0.6 |
| VAL + AHU 50 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maDBP | -5.79 mmHg | Standard Error 0.61 |
| VAL + AHU 50 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maSBP | -12.17 mmHg | Standard Error 0.99 |
| VAL 320 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maSBP | -9.73 mmHg | Standard Error 0.96 |
| VAL 320 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maDBP | -5.10 mmHg | Standard Error 0.59 |
| LCZ 400 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maSBP | -13.12 mmHg | Standard Error 0.96 |
| LCZ 400 mg | Change From Baseline in maSBP and maDBP in Non-dippers | maDBP | -6.34 mmHg | Standard Error 0.59 |
| Placebo | Change From Baseline in maSBP and maDBP in Non-dippers | maSBP | -1.46 mmHg | Standard Error 1.75 |
| Placebo | Change From Baseline in maSBP and maDBP in Non-dippers | maDBP | -0.49 mmHg | Standard Error 1.08 |
Secondary
Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age
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.
Time frame: Baseline, 8 weeks
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maDBP | -6.74 mmHg | Standard Error 0.67 |
| VAL + AHU 400 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maSBP | -12.16 mmHg | Standard Error 0.98 |
| VAL + AHU 200 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maDBP | -7.81 mmHg | Standard Error 0.62 |
| VAL + AHU 200 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maSBP | -15.06 mmHg | Standard Error 0.91 |
| VAL + AHU 100 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maSBP | -14.42 mmHg | Standard Error 0.95 |
| VAL + AHU 100 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maDBP | -7.93 mmHg | Standard Error 0.65 |
| VAL + AHU 50 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maSBP | -10.39 mmHg | Standard Error 0.95 |
| VAL + AHU 50 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maDBP | -5.69 mmHg | Standard Error 0.65 |
| VAL 320 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maSBP | -9.55 mmHg | Standard Error 0.99 |
| VAL 320 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maDBP | -5.94 mmHg | Standard Error 0.67 |
| LCZ 400 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maSBP | -13.98 mmHg | Standard Error 0.93 |
| LCZ 400 mg | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maDBP | -7.32 mmHg | Standard Error 0.63 |
| Placebo | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maSBP | -2.24 mmHg | Standard Error 1.67 |
| Placebo | Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age | maDBP | -1.53 mmHg | Standard Error 1.14 |
Secondary
Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age
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.
Time frame: Baseline, 8 weeks
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maSBP | -12.10 mmHg | Standard Error 1.04 |
| VAL + AHU 400 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maDBP | -4.94 mmHg | Standard Error 0.58 |
| VAL + AHU 200 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maSBP | -16.08 mmHg | Standard Error 1.03 |
| VAL + AHU 200 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maDBP | -6.00 mmHg | Standard Error 0.57 |
| VAL + AHU 100 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maSBP | -14.20 mmHg | Standard Error 1.08 |
| VAL + AHU 100 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maDBP | -4.86 mmHg | Standard Error 0.6 |
| VAL + AHU 50 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maSBP | -12.25 mmHg | Standard Error 1.04 |
| VAL + AHU 50 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maDBP | -4.93 mmHg | Standard Error 0.58 |
| VAL 320 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maSBP | -9.73 mmHg | Standard Error 1.02 |
| VAL 320 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maDBP | -4.58 mmHg | Standard Error 0.56 |
| LCZ 400 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maSBP | -11.88 mmHg | Standard Error 1.1 |
| LCZ 400 mg | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maDBP | -5.04 mmHg | Standard Error 0.61 |
| Placebo | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maSBP | -1.95 mmHg | Standard Error 1.59 |
| Placebo | Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age | maDBP | -0.01 mmHg | Standard Error 0.88 |
Secondary
Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP)
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.
Time frame: Baseline, 8 weeks
Population: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | 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 |
| VAL + AHU 400 mg | 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 |
| VAL + AHU 200 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maSBP | -15.66 mmHg | Standard Error 0.69 |
| VAL + AHU 200 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maDBP | -7.03 mmHg | Standard Error 0.42 |
| VAL + AHU 100 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maSBP | -14.33 mmHg | Standard Error 0.72 |
| VAL + AHU 100 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maDBP | -6.46 mmHg | Standard Error 0.44 |
| VAL + AHU 50 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maSBP | -11.36 mmHg | Standard Error 0.7 |
| VAL + AHU 50 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maDBP | -5.36 mmHg | Standard Error 0.43 |
| VAL 320 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maSBP | -9.59 mmHg | Standard Error 0.71 |
| VAL 320 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maDBP | -5.23 mmHg | Standard Error 0.44 |
| LCZ 400 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maSBP | -12.98 mmHg | Standard Error 0.71 |
| LCZ 400 mg | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maDBP | -6.20 mmHg | Standard Error 0.44 |
| Placebo | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maSBP | -2.12 mmHg | Standard Error 1.15 |
| Placebo | Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP) | maDBP | -0.79 mmHg | Standard Error 0.71 |
Secondary
Change From Baseline in Mean Ambulatory Pulse Pressure
Pulse rate measurements were performed. A negative change from baseline indicates improvement.
Time frame: Baseline, 8 weeks
Population: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in Mean Ambulatory Pulse Pressure | -6.23 mmHg | Standard Error 0.39 |
| VAL + AHU 200 mg | Change From Baseline in Mean Ambulatory Pulse Pressure | -8.51 mmHg | Standard Error 0.38 |
| VAL + AHU 100 mg | Change From Baseline in Mean Ambulatory Pulse Pressure | -7.71 mmHg | Standard Error 0.4 |
| VAL + AHU 50 mg | Change From Baseline in Mean Ambulatory Pulse Pressure | -6.00 mmHg | Standard Error 0.39 |
| VAL 320 mg | Change From Baseline in Mean Ambulatory Pulse Pressure | -4.40 mmHg | Standard Error 0.39 |
| LCZ 400 mg | Change From Baseline in Mean Ambulatory Pulse Pressure | -6.84 mmHg | Standard Error 0.39 |
| Placebo | Change From Baseline in Mean Ambulatory Pulse Pressure | -1.09 mmHg | Standard Error 0.63 |
Secondary
Change From Baseline in Mean Diastolic Blood Pressure (msDBP)
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Time frame: Baseline, 8 weeks
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in Mean Diastolic Blood Pressure (msDBP) | -8.47 mmHg | Standard Error 0.76 |
| VAL + AHU 200 mg | Change From Baseline in Mean Diastolic Blood Pressure (msDBP) | -9.76 mmHg | Standard Error 0.75 |
| VAL + AHU 100 mg | Change From Baseline in Mean Diastolic Blood Pressure (msDBP) | -8.04 mmHg | Standard Error 0.76 |
| VAL + AHU 50 mg | Change From Baseline in Mean Diastolic Blood Pressure (msDBP) | -7.15 mmHg | Standard Error 0.79 |
| VAL 320 mg | Change From Baseline in Mean Diastolic Blood Pressure (msDBP) | -7.28 mmHg | Standard Error 0.76 |
| LCZ 400 mg | Change From Baseline in Mean Diastolic Blood Pressure (msDBP) | -9.61 mmHg | Standard Error 0.75 |
| Placebo | Change From Baseline in Mean Diastolic Blood Pressure (msDBP) | -3.38 mmHg | Standard Error 1.19 |
Secondary
Change From Baseline in Mean Sitting Pulse Pressure
Pulse rate measurements were performed. A negative change from baseline indicates improvement.
Time frame: Baseline, 8 weeks
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in Mean Sitting Pulse Pressure | -12.39 mmHg | Standard Error 0.91 |
| VAL + AHU 200 mg | Change From Baseline in Mean Sitting Pulse Pressure | -13.91 mmHg | Standard Error 0.9 |
| VAL + AHU 100 mg | Change From Baseline in Mean Sitting Pulse Pressure | -13.18 mmHg | Standard Error 0.91 |
| VAL + AHU 50 mg | Change From Baseline in Mean Sitting Pulse Pressure | -12.01 mmHg | Standard Error 0.95 |
| VAL 320 mg | Change From Baseline in Mean Sitting Pulse Pressure | -8.80 mmHg | Standard Error 0.91 |
| LCZ 400 mg | Change From Baseline in Mean Sitting Pulse Pressure | -12.18 mmHg | Standard Error 0.91 |
| Placebo | Change From Baseline in Mean Sitting Pulse Pressure | -3.74 mmHg | Standard Error 1.43 |
Secondary
Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Time frame: Baseline, 8 weeks
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msSBP | -20.95 mmHg | Standard Error 1.68 |
| VAL + AHU 400 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msDBP | -8.97 mmHg | Standard Error 1.11 |
| VAL + AHU 200 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msSBP | -24.45 mmHg | Standard Error 1.67 |
| VAL + AHU 200 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msDBP | -10.94 mmHg | Standard Error 1.11 |
| VAL + AHU 100 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msSBP | -20.94 mmHg | Standard Error 1.63 |
| VAL + AHU 100 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msDBP | -8.83 mmHg | Standard Error 1.09 |
| VAL + AHU 50 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msSBP | -18.09 mmHg | Standard Error 1.79 |
| VAL + AHU 50 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msDBP | -8.07 mmHg | Standard Error 1.19 |
| VAL 320 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msSBP | -16.96 mmHg | Standard Error 1.71 |
| VAL 320 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msDBP | -6.93 mmHg | Standard Error 1.13 |
| LCZ 400 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msSBP | -21.06 mmHg | Standard Error 1.63 |
| LCZ 400 mg | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msDBP | -10.25 mmHg | Standard Error 1.08 |
| Placebo | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msSBP | -8.94 mmHg | Standard Error 2.73 |
| Placebo | Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age | msDBP | -5.19 mmHg | Standard Error 1.82 |
Secondary
Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age
Sitting BP measurements were performed at trough (23-26 hours post-morning dose). A negative change from baseline indicates improvement.
Time frame: Baseline, 8 weeks
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msSBP | -20.93 mmHg | Standard Error 1.79 |
| VAL + AHU 400 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msDBP | -7.89 mmHg | Standard Error 1.02 |
| VAL + AHU 200 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msSBP | -22.66 mmHg | Standard Error 1.76 |
| VAL + AHU 200 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msDBP | -8.44 mmHg | Standard Error 1 |
| VAL + AHU 100 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msSBP | -21.72 mmHg | Standard Error 1.85 |
| VAL + AHU 100 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msDBP | -7.06 mmHg | Standard Error 1.05 |
| VAL + AHU 50 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msSBP | -20.64 mmHg | Standard Error 1.81 |
| VAL + AHU 50 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msDBP | -6.17 mmHg | Standard Error 1.03 |
| VAL 320 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msSBP | -15.48 mmHg | Standard Error 1.75 |
| VAL 320 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msDBP | -7.62 mmHg | Standard Error 0.99 |
| LCZ 400 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msSBP | -22.83 mmHg | Standard Error 1.84 |
| LCZ 400 mg | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msDBP | -8.89 mmHg | Standard Error 1.04 |
| Placebo | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msSBP | -5.10 mmHg | Standard Error 2.71 |
| Placebo | Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age | msDBP | -1.46 mmHg | Standard Error 1.54 |
Secondary
Change From Baseline in Nighttime maSBP and maDBP
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.
Time frame: Baseline and 8 weeks
Population: A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| VAL + AHU 400 mg | Change From Baseline in Nighttime maSBP and maDBP | maSBP | -11.57 mmHg | Standard Error 1.23 |
| VAL + AHU 400 mg | Change From Baseline in Nighttime maSBP and maDBP | maDBP | -5.27 mmHg | Standard Error 0.78 |
| VAL + AHU 200 mg | Change From Baseline in Nighttime maSBP and maDBP | maSBP | -15.27 mmHg | Standard Error 1.19 |
| VAL + AHU 200 mg | Change From Baseline in Nighttime maSBP and maDBP | maDBP | -6.79 mmHg | Standard Error 0.75 |
| VAL + AHU 100 mg | Change From Baseline in Nighttime maSBP and maDBP | maSBP | -14.74 mmHg | Standard Error 1.23 |
| VAL + AHU 100 mg | Change From Baseline in Nighttime maSBP and maDBP | maDBP | -6.45 mmHg | Standard Error 0.78 |
| VAL + AHU 50 mg | Change From Baseline in Nighttime maSBP and maDBP | maSBP | -10.80 mmHg | Standard Error 1.21 |
| VAL + AHU 50 mg | Change From Baseline in Nighttime maSBP and maDBP | maDBP | -5.27 mmHg | Standard Error 0.77 |
| VAL 320 mg | Change From Baseline in Nighttime maSBP and maDBP | maSBP | -8.88 mmHg | Standard Error 1.22 |
| VAL 320 mg | Change From Baseline in Nighttime maSBP and maDBP | maDBP | -4.49 mmHg | Standard Error 0.77 |
| LCZ 400 mg | Change From Baseline in Nighttime maSBP and maDBP | maSBP | -12.34 mmHg | Standard Error 1.23 |
| LCZ 400 mg | Change From Baseline in Nighttime maSBP and maDBP | maDBP | -6.36 mmHg | Standard Error 0.78 |
| Placebo | Change From Baseline in Nighttime maSBP and maDBP | maSBP | -1.36 mmHg | Standard Error 1.98 |
| Placebo | Change From Baseline in Nighttime maSBP and maDBP | maDBP | -0.22 mmHg | Standard Error 1.26 |
Secondary
Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response
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.
Time frame: 8 weeks
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAL + AHU 400 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msDBP response | 112 Number of participants |
| VAL + AHU 400 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msSBP response | 88 Number of participants |
| VAL + AHU 400 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | Blood pressure control | 72 Number of participants |
| VAL + AHU 200 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msSBP response | 101 Number of participants |
| VAL + AHU 200 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | Blood pressure control | 86 Number of participants |
| VAL + AHU 200 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msDBP response | 126 Number of participants |
| VAL + AHU 100 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msDBP response | 114 Number of participants |
| VAL + AHU 100 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | Blood pressure control | 71 Number of participants |
| VAL + AHU 100 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msSBP response | 93 Number of participants |
| VAL + AHU 50 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msSBP response | 81 Number of participants |
| VAL + AHU 50 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | Blood pressure control | 58 Number of participants |
| VAL + AHU 50 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msDBP response | 101 Number of participants |
| VAL 320 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msSBP response | 72 Number of participants |
| VAL 320 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | Blood pressure control | 57 Number of participants |
| VAL 320 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msDBP response | 111 Number of participants |
| LCZ 400 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | Blood pressure control | 76 Number of participants |
| LCZ 400 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msDBP response | 118 Number of participants |
| LCZ 400 mg | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msSBP response | 94 Number of participants |
| Placebo | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msDBP response | 39 Number of participants |
| Placebo | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | msSBP response | 11 Number of participants |
| Placebo | Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response | Blood pressure control | 8 Number of participants |
Secondary
Number of Participants With Adverse Events, Serious Adverse Events and Death
Adverse event monitoring was conducted throughout the study.
Time frame: 8 weeks
Population: Safety Analysis Set: The safety analysis set included all randomized participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAL + AHU 400 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Deaths | 1 Number of participants |
| VAL + AHU 400 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 3 Number of participants |
| VAL + AHU 400 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Adverse events (non-serious and serious) | 40 Number of participants |
| VAL + AHU 200 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 1 Number of participants |
| VAL + AHU 200 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Adverse events (non-serious and serious) | 31 Number of participants |
| VAL + AHU 200 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Deaths | 0 Number of participants |
| VAL + AHU 100 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Deaths | 0 Number of participants |
| VAL + AHU 100 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Adverse events (non-serious and serious) | 29 Number of participants |
| VAL + AHU 100 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 1 Number of participants |
| VAL + AHU 50 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 0 Number of participants |
| VAL + AHU 50 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Adverse events (non-serious and serious) | 25 Number of participants |
| VAL + AHU 50 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Deaths | 0 Number of participants |
| VAL 320 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 1 Number of participants |
| VAL 320 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Adverse events (non-serious and serious) | 38 Number of participants |
| VAL 320 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Deaths | 0 Number of participants |
| LCZ 400 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Adverse events (non-serious and serious) | 42 Number of participants |
| LCZ 400 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Deaths | 0 Number of participants |
| LCZ 400 mg | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 1 Number of participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events and Death | Deaths | 0 Number of participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events and Death | Serious adverse events | 1 Number of participants |
| Placebo | Number of Participants With Adverse Events, Serious Adverse Events and Death | Adverse events (non-serious and serious) | 20 Number of participants |