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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01281306
Recruitment Status : Completed
First Posted : January 21, 2011
Results First Posted : August 18, 2015
Last Update Posted : January 29, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Systolic Hypertension
Interventions Drug: LCZ696
Drug: Valsartan
Drug: AHU377
Drug: Placebo
Enrollment 910
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.
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description 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. 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. 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. 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. 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. 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. Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Period Title: Overall Study
Started 144 145 141 134 143 142 58
Full Analysis Set 143 145 141 133 143 142 58
Safety Set 143 145 141 133 143 142 58
Ambulatory Blood Pressure Monitoring Set 95 99 92 95 93 91 35
Completed 136 141 133 123 134 135 51
Not Completed 8 4 8 11 9 7 7
Reason Not Completed
Lack of Efficacy             0             1             3             0             2             0             1
Withdrawal by Subject             1             0             2             4             1             3             1
Protocol deviation             0             1             1             1             1             0             0
Condition no longer requires study drug             1             0             0             0             0             1             1
Lost to Follow-up             1             0             0             2             0             0             1
Death             1             0             0             0             0             0             0
Adverse Event             3             2             2             3             5             3             3
Randomized in error             1             0             0             1             0             0             0
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo Total
Hide Arm/Group Description 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. 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. 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. 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. 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. 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. Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 144 145 141 134 143 142 58 907
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 144 participants 145 participants 141 participants 134 participants 143 participants 142 participants 58 participants 907 participants
61.7  (11.36) 61.7  (11.44) 61.0  (11.03) 62.0  (10.73) 62.0  (11.45) 61.2  (10.60) 60.8  (11.81) 61.5  (11.13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 144 participants 145 participants 141 participants 134 participants 143 participants 142 participants 58 participants 907 participants
Female
78
  54.2%
60
  41.4%
53
  37.6%
61
  45.5%
60
  42.0%
71
  50.0%
29
  50.0%
412
  45.4%
Male
66
  45.8%
85
  58.6%
88
  62.4%
73
  54.5%
83
  58.0%
71
  50.0%
29
  50.0%
495
  54.6%
1.Primary Outcome
Title Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 143 144 141 132 143 142 57
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-20.89  (1.22) -23.55  (1.21) -21.26  (1.23) -19.31  (1.27) -16.13  (1.22) -21.78  (1.22) -6.99  (1.92)
2.Secondary Outcome
Title Change From Baseline in Mean Diastolic Blood Pressure (msDBP)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 143 144 141 132 143 142 57
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-8.47  (0.76) -9.76  (0.75) -8.04  (0.76) -7.15  (0.79) -7.28  (0.76) -9.61  (0.75) -3.38  (1.19)
3.Secondary Outcome
Title Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 94 98 92 95 93 90 35
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
maSBP -12.14  (0.71) -15.66  (0.69) -14.33  (0.72) -11.36  (0.70) -9.59  (0.71) -12.98  (0.71) -2.12  (1.15)
maDBP -5.81  (0.44) -7.03  (0.42) -6.46  (0.44) -5.36  (0.43) -5.23  (0.44) -6.20  (0.44) -0.79  (0.71)
4.Secondary Outcome
Title Change From Baseline in Daytime maSBP and maDBP
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 94 98 92 95 93 90 35
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
maSBP -12.62  (1.21) -15.85  (1.19) -14.43  (1.23) -11.50  (1.21) -9.60  (1.22) -13.32  (1.23) -2.39  (1.98)
maDBP -5.93  (0.77) -7.13  (0.75) -6.57  (0.78) -5.39  (0.77) -5.40  (0.77) -6.16  (0.78) -0.98  (1.26)
5.Secondary Outcome
Title Change From Baseline in Nighttime maSBP and maDBP
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 91 98 90 95 92 90 35
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
maSBP -11.57  (1.23) -15.27  (1.19) -14.74  (1.23) -10.80  (1.21) -8.88  (1.22) -12.34  (1.23) -1.36  (1.98)
maDBP -5.27  (0.78) -6.79  (0.75) -6.45  (0.78) -5.27  (0.77) -4.49  (0.77) -6.36  (0.78) -0.22  (1.26)
6.Secondary Outcome
Title Change From Baseline in Mean Sitting Pulse Pressure
Hide Description Pulse rate measurements were performed. A negative change from baseline indicates improvement.
Time Frame Baseline, 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 143 144 141 132 143 142 57
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-12.39  (0.91) -13.91  (0.90) -13.18  (0.91) -12.01  (0.95) -8.80  (0.91) -12.18  (0.91) -3.74  (1.43)
7.Secondary Outcome
Title Change From Baseline in Mean Ambulatory Pulse Pressure
Hide Description Pulse rate measurements were performed. A negative change from baseline indicates improvement.
Time Frame Baseline, 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 94 98 92 95 93 90 35
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
-6.23  (0.39) -8.51  (0.38) -7.71  (0.40) -6.00  (0.39) -4.40  (0.39) -6.84  (0.39) -1.09  (0.63)
8.Secondary Outcome
Title Change From Baseline in maSBP and maDBP in Dippers
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 32 42 38 42 38 37 19
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
maSBP -11.43  (1.12) -15.59  (1.00) -12.04  (1.05) 10.60  (1.01) -9.85  (1.03) -13.09  (1.05) -2.39  (1.45)
maDBP -4.62  (0.70) -7.33  (0.62) -5.49  (0.65) -5.07  (0.63) -5.53  (0.64) -6.03  (0.65) -0.98  (0.90)
9.Secondary Outcome
Title Change From Baseline in maSBP and maDBP in Non-dippers
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of randomized participants, who had ABPM measurements at both baseline and week 8, were included in the analysis.
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 59 56 53 53 54 53 16
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
maSBP -12.81  (0.91) -16.08  (0.94) -16.37  (0.97) -12.17  (0.99) -9.73  (0.96) -13.12  (0.96) -1.46  (1.75)
maDBP -6.65  (0.56) -6.91  (0.58) -7.31  (0.60) -5.79  (0.61) -5.10  (0.59) -6.34  (0.59) -0.49  (1.08)
10.Secondary Outcome
Title Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 75 75 78 66 73 79 28
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
msSBP -20.95  (1.68) -24.45  (1.67) -20.94  (1.63) -18.09  (1.79) -16.96  (1.71) -21.06  (1.63) -8.94  (2.73)
msDBP -8.97  (1.11) -10.94  (1.11) -8.83  (1.09) -8.07  (1.19) -6.93  (1.13) -10.25  (1.08) -5.19  (1.82)
11.Secondary Outcome
Title Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 68 69 63 66 70 63 29
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
msSBP -20.93  (1.79) -22.66  (1.76) -21.72  (1.85) -20.64  (1.81) -15.48  (1.75) -22.83  (1.84) -5.10  (2.71)
msDBP -7.89  (1.02) -8.44  (1.00) -7.06  (1.05) -6.17  (1.03) -7.62  (0.99) -8.89  (1.04) -1.46  (1.54)
12.Secondary Outcome
Title Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 44 50 46 47 44 48 15
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
maSBP -12.16  (0.98) -15.06  (0.91) -14.42  (0.95) -10.39  (0.95) -9.55  (0.99) -13.98  (0.93) -2.24  (1.67)
maDBP -6.74  (0.67) -7.81  (0.62) -7.93  (0.65) -5.69  (0.65) -5.94  (0.67) -7.32  (0.63) -1.53  (1.14)
13.Secondary Outcome
Title Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 50 48 46 48 49 42 20
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
maSBP -12.10  (1.04) -16.08  (1.03) -14.20  (1.08) -12.25  (1.04) -9.73  (1.02) -11.88  (1.10) -1.95  (1.59)
maDBP -4.94  (0.58) -6.00  (0.57) -4.86  (0.60) -4.93  (0.58) -4.58  (0.56) -5.04  (0.61) -0.01  (0.88)
14.Secondary Outcome
Title Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 143 144 141 132 143 142 57
Measure Type: Number
Unit of Measure: Number of participants
Blood pressure control 72 86 71 58 57 76 8
msSBP response 88 101 93 81 72 94 11
msDBP response 112 126 114 101 111 118 39
15.Secondary Outcome
Title Number of Participants With Adverse Events, Serious Adverse Events and Death
Hide Description Adverse event monitoring was conducted throughout the study.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: The safety analysis set included all randomized participants who received at least one dose of study medication.
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description:
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.
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.
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.
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.
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.
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.
Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
Overall Number of Participants Analyzed 143 145 141 133 143 142 58
Measure Type: Number
Unit of Measure: Number of participants
Adverse events (non-serious and serious) 40 31 29 25 38 42 20
Serious adverse events 3 1 1 0 1 1 1
Deaths 1 0 0 0 0 0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Hide Arm/Group Description 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. 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. 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. 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. 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. 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. Participants received matching placebo to LCZ696, AHU377 and valsartan for 8 weeks.
All-Cause Mortality
VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/143 (2.10%)   1/145 (0.69%)   1/141 (0.71%)   0/133 (0.00%)   1/143 (0.70%)   1/142 (0.70%)   1/58 (1.72%) 
General disorders               
Sudden death  1  1/143 (0.70%)  0/145 (0.00%)  0/141 (0.00%)  0/133 (0.00%)  0/143 (0.00%)  0/142 (0.00%)  0/58 (0.00%) 
Hepatobiliary disorders               
Cholelithiasis  1  1/143 (0.70%)  0/145 (0.00%)  0/141 (0.00%)  0/133 (0.00%)  0/143 (0.00%)  0/142 (0.00%)  0/58 (0.00%) 
Infections and infestations               
Postoperative wound infection  1  0/143 (0.00%)  0/145 (0.00%)  1/141 (0.71%)  0/133 (0.00%)  0/143 (0.00%)  0/142 (0.00%)  0/58 (0.00%) 
Injury, poisoning and procedural complications               
Thoracic vertebral fracture  1  0/143 (0.00%)  0/145 (0.00%)  0/141 (0.00%)  0/133 (0.00%)  1/143 (0.70%)  0/142 (0.00%)  0/58 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Colon cancer  1  0/143 (0.00%)  0/145 (0.00%)  0/141 (0.00%)  0/133 (0.00%)  0/143 (0.00%)  1/142 (0.70%)  0/58 (0.00%) 
Psychiatric disorders               
Schizophrenia  1  0/143 (0.00%)  1/145 (0.69%)  0/141 (0.00%)  0/133 (0.00%)  0/143 (0.00%)  0/142 (0.00%)  0/58 (0.00%) 
Renal and urinary disorders               
Calculus urinary  1  0/143 (0.00%)  0/145 (0.00%)  0/141 (0.00%)  0/133 (0.00%)  0/143 (0.00%)  0/142 (0.00%)  1/58 (1.72%) 
Skin and subcutaneous tissue disorders               
Angioedema  1  1/143 (0.70%)  0/145 (0.00%)  0/141 (0.00%)  0/133 (0.00%)  0/143 (0.00%)  0/142 (0.00%)  0/58 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
VAL + AHU 400 mg VAL + AHU 200 mg VAL + AHU 100 mg VAL + AHU 50 mg VAL 320 mg LCZ 400 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/143 (0.70%)   2/145 (1.38%)   1/141 (0.71%)   2/133 (1.50%)   4/143 (2.80%)   1/142 (0.70%)   3/58 (5.17%) 
Gastrointestinal disorders               
Dyspepsia  1  1/143 (0.70%)  2/145 (1.38%)  1/141 (0.71%)  2/133 (1.50%)  4/143 (2.80%)  1/142 (0.70%)  3/58 (5.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01281306    
Other Study ID Numbers: CLCZ696A2223
2010-022326-32
First Submitted: January 20, 2011
First Posted: January 21, 2011
Results First Submitted: July 21, 2015
Results First Posted: August 18, 2015
Last Update Posted: January 29, 2016