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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01281306
First received: January 20, 2011
Last updated: July 21, 2015
Last verified: July 2015
Results First Received: July 21, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Systolic Hypertension
Interventions: Drug: LCZ696
Drug: Valsartan
Drug: AHU377
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study consisted of a single-blind run-in period and a double-blind period. During the 3 to 4 week run-in, participants were assessed for randomization eligibility into the double-blind period.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    VAL + AHU 400 mg     VAL + AHU 200 mg     VAL + AHU 100 mg     VAL + AHU 50 mg     VAL 320 mg     LCZ 400 mg     Placebo  
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  
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  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    VAL + AHU 400 mg     VAL + AHU 200 mg     VAL + AHU 100 mg     VAL + AHU 50 mg     VAL 320 mg     LCZ 400 mg     Placebo     Total  
Number of Participants  
[units: participants]
  144     145     141     134     143     142     58     907  
Age  
[units: Years]
Mean (Standard Deviation)
  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)  
Gender  
[units: Participants]
               
Female     78     60     53     61     60     71     29     412  
Male     66     85     88     73     83     71     29     495  



  Outcome Measures
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1.  Primary:   Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline, 8 weeks ]

2.  Secondary:   Change From Baseline in Mean Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline, 8 weeks ]

3.  Secondary:   Change From Baseline in Mean 24 Hour Ambulatory SBP (maSBP) and Mean 24 Hour Ambulatory DBP (maDBP)   [ Time Frame: Baseline, 8 weeks ]

4.  Secondary:   Change From Baseline in Daytime maSBP and maDBP   [ Time Frame: Baseline, 8 weeks ]

5.  Secondary:   Change From Baseline in Nighttime maSBP and maDBP   [ Time Frame: Baseline and 8 weeks ]

6.  Secondary:   Change From Baseline in Mean Sitting Pulse Pressure   [ Time Frame: Baseline, 8 weeks ]

7.  Secondary:   Change From Baseline in Mean Ambulatory Pulse Pressure   [ Time Frame: Baseline, 8 weeks ]

8.  Secondary:   Change From Baseline in maSBP and maDBP in Dippers   [ Time Frame: Baseline, 8 weeks ]

9.  Secondary:   Change From Baseline in maSBP and maDBP in Non-dippers   [ Time Frame: Baseline, 8 weeks ]

10.  Secondary:   Change From Baseline in msSBP and msDBP in Participants < 65 Years of Age   [ Time Frame: Baseline, 8 weeks ]

11.  Secondary:   Change From Baseline in msSBP and msDBP in Participants >= 65 Years of Age   [ Time Frame: Baseline, 8 weeks ]

12.  Secondary:   Change From Baseline in maSBP and maDBP in Participants < 65 Years of Age   [ Time Frame: Baseline, 8 weeks ]

13.  Secondary:   Change From Baseline in maSBP and maDBP in Participants >= 65 Years of Age   [ Time Frame: Baseline, 8 weeks ]

14.  Secondary:   Number of Participants Who Achieved Blood Pressure Control and Blood Pressure Response   [ Time Frame: 8 weeks ]

15.  Secondary:   Number of Participants With Adverse Events, Serious Adverse Events and Death   [ Time Frame: 8 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis
phone: 862-778-8300


No publications provided


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01281306     History of Changes
Other Study ID Numbers: CLCZ696A2223, 2010-022326-32
Study First Received: January 20, 2011
Results First Received: July 21, 2015
Last Updated: July 21, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Human Research Bioethics Committee
Canada: Therapeutic Products Directorate at Health Canada
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency of Medicine (Agentia Nationala a Medicamentului)
South Korea: Korea Food and Drug Administration (KFDA)
Slovakia: State Institute for Drug Control
Spain: Agencia Espanola del Medicamento y Productos Sanitarios (AEMPS)