Efficacy and Safety of LCZ696A in Patients With Essential Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00549770
First received: October 5, 2007
Last updated: August 11, 2015
Last verified: August 2015
Results First Received: August 10, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: 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
The study comprised 3 periods: a 4-week washout and placebo run-in period (pre-randomization), an 8-week randomized, double-blind monotherapy period, and 1-week randomized, placebo-controlled withdrawal period. In the randomized withdrawal, participants were either randomized to placebo or continued their original assigned treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After successful completion of the pre-randomization period, participants were randomized 1:1:1:1:1:1:1:1 ratio to one of 8 treatment groups.

Reporting Groups
  Description
LCZ696 100 mg Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 200 mg Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 400 mg Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 80 mg Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 160 mg Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 320 mg Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
AHU377 200 mg Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
Placebo Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.

Participant Flow:   Overall Study
    LCZ696 100 mg     LCZ696 200 mg     LCZ696 400 mg     Valsartan 80 mg     Valsartan 160 mg     Valsartan 320 mg     AHU377 200 mg     Placebo  
STARTED     156     169     172     163     166     164     165     173  
Intent-to-treat Population     154     168     170     163     163     163     164     172  
Ambulatory Blood Pressure Monitoring     48     61     53     55     49     54     50     57  
COMPLETED     149     158     162     147     149     151     151     148  
NOT COMPLETED     7     11     10     16     17     13     14     25  
Protocol deviation                 1                 1                 1                 2                 2                 2                 1                 2  
Administrative problems                 0                 1                 0                 0                 0                 0                 0                 1  
Lost to Follow-up                 0                 0                 2                 2                 3                 2                 0                 0  
Withdrawal by Subject                 4                 6                 4                 5                 6                 6                 4                 9  
Lack of Efficacy                 1                 0                 2                 3                 5                 1                 3                 8  
Abnormal test procedure results                 0                 0                 0                 2                 0                 1                 1                 1  
Abnormal laboratory values                 0                 0                 0                 0                 0                 1                 0                 0  
Adverse Event                 1                 3                 1                 2                 1                 0                 5                 4  



  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
LCZ696 100 mg Participants received LCZ696 100 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 200 mg Participants received LCZ696 200 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
LCZ696 400 mg Participants received LCZ696 400 mg (200 mg LCZ696 for one week and then up-titration to 400 mg LCZ696 for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 80 mg Participants received Valsartan 80 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 160 mg Participants received Valsartan 160 mg and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Valsartan 320 mg Participants received Valsartan 320 mg (160 mg valsartan capsules for one week followed by 320 mg valsartan capsules for 7 weeks) and matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
AHU377 200 mg Participants received AHU377 200 mg and matching placebo to LCZ696 and Valsartan (5 tablets and 2 capsules) daily.
Placebo Participants received matching placebo to LCZ696, Valsartan and AHU377 (5 tablets and 2 capsules) daily.
Total Total of all reporting groups

Baseline Measures
    LCZ696 100 mg     LCZ696 200 mg     LCZ696 400 mg     Valsartan 80 mg     Valsartan 160 mg     Valsartan 320 mg     AHU377 200 mg     Placebo     Total  
Number of Participants  
[units: participants]
  156     169     172     163     166     164     165     173     1328  
Age  
[units: years]
Mean (Standard Deviation)
  53  (10.4)     54  (9.7)     52  (10.9)     53  (9.6)     53  (9.7)     53  (10.1)     53  (10.7)     54  (10.6)     53  (10.2)  
Gender  
[units: participants]
                 
Female     61     77     75     68     68     65     75     79     568  
Male     95     92     97     95     98     99     90     94     760  



  Outcome Measures
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1.  Primary:   Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: baseline, week 8 ]

2.  Secondary:   Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: baseline, week 8 ]

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

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

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

6.  Secondary:   Percentage of Participants Who Achieved a Successful Response in msDBP   [ Time Frame: 8 weeks ]

7.  Secondary:   Percentage of Participants Who Achieved a Successful Response in msSBP   [ Time Frame: 8 weeks ]

8.  Secondary:   Percentage of Participants Who Achieved Successful Control in msDBP   [ Time Frame: 8 weeks ]

9.  Secondary:   Percentage of Participants Who Achieved Successful Control in msSBP   [ 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 Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00549770     History of Changes
Other Study ID Numbers: CLCZ696A2201
Study First Received: October 5, 2007
Results First Received: August 10, 2012
Last Updated: August 11, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Canada: Health Canada
Denmark: Danish Health Authorities
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: The Central Register of Clinical Trials
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Taiwan: Department of Health