Study to Evaluate the Efficacy and Safety of Aliskiren Alone and in Combination With Amlodipine in Essential Hypertension

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00739973
First received: August 20, 2008
Last updated: June 2, 2011
Last verified: June 2011
Results First Received: January 13, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Hypertension
Interventions: Drug: Placebo
Drug: Aliskiren 150 mg tablet
Drug: Aliskiren 300 mg tablet
Drug: Amlodipine 5 mg capsule
Drug: Amlodipine 10 mg capsule
Drug: Aliskiren/amlodipine 150/5 mg tablet
Drug: Aliskiren/amlodipine 150/10 mg tablet
Drug: Aliskiren/amlodipine 300/5 mg tablet
Drug: Aliskiren/amlodipine 300/10 mg tablet

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 2694 patients enrolled in the single-blind, placebo run-in period (2 to 4 weeks) of the study. A total of 1688 patients were randomized into the double-blind treatment period (8 weeks). Three patients were mis-randomized, as they were discontinued from the single-blind period and were not treated in the double-blind period.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; for this arm all the 5 pills taken were placebos.
Aliskiren 150 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Aliskiren 300 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Amlodipine 5 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Amlodipine 10 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos. Amlodipine 10 mg arm starts with 1 week of Amlodipine 5 mg, then force titrated to 10 mg.
Aliskiren/Amlodipine 150/5 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Aliskiren/Amlodipine 150/10 mg 150/5 for 1 week, then up-titrated to 150/10 mg. Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Aliskiren/Amlodipine 300/5 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Aliskiren/Amlodipine 300/10 mg Tablet 300/5 for 1 week, then up-titrated to 300/10 mg. Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.

Participant Flow for 2 periods

Period 1:   Single-blind Period (2 to 4 Weeks)
    Placebo     Aliskiren 150 mg     Aliskiren 300 mg     Amlodipine 5 mg     Amlodipine 10 mg     Aliskiren/Amlodipine 150/5 mg     Aliskiren/Amlodipine 150/10 mg     Aliskiren/Amlodipine 300/5 mg     Aliskiren/Amlodipine 300/10 mg Tablet  
STARTED     2694 [1]   0     0     0     0     0     0     0     0  
COMPLETED     1685     0     0     0     0     0     0     0     0  
NOT COMPLETED     1009     0     0     0     0     0     0     0     0  
Adverse Event                 35                 0                 0                 0                 0                 0                 0                 0                 0  
Abnormal laboratory value(s)                 38                 0                 0                 0                 0                 0                 0                 0                 0  
Abnormal test procedure result(s)                 810                 0                 0                 0                 0                 0                 0                 0                 0  
Patient withdrew consent                 86                 0                 0                 0                 0                 0                 0                 0                 0  
Lost to Follow-up                 17                 0                 0                 0                 0                 0                 0                 0                 0  
Administrative problems                 12                 0                 0                 0                 0                 0                 0                 0                 0  
Protocol deviation                 11                 0                 0                 0                 0                 0                 0                 0                 0  
[1] In this period, participants were enrolled to only Placebo arm.

Period 2:   Double-blind:Randomized Period (8 Weeks)
    Placebo     Aliskiren 150 mg     Aliskiren 300 mg     Amlodipine 5 mg     Amlodipine 10 mg     Aliskiren/Amlodipine 150/5 mg     Aliskiren/Amlodipine 150/10 mg     Aliskiren/Amlodipine 300/5 mg     Aliskiren/Amlodipine 300/10 mg Tablet  
STARTED     198     195 [1]   203     185     181     181     183 [2]   178     184  
COMPLETED     168     175     184     173     162     169     170     168     170  
NOT COMPLETED     30     20     19     12     19     12     13     10     14  
Adverse Event                 3                 3                 1                 2                 7                 3                 4                 1                 4  
Abnormal laboratory values                 0                 0                 0                 0                 1                 0                 0                 1                 0  
Abnormal test procedure results                 1                 1                 0                 0                 0                 0                 0                 0                 0  
Unsatisfactory therapeutic effect                 17                 8                 8                 4                 2                 2                 1                 1                 2  
Patient no longer needs study drug                 0                 0                 1                 0                 0                 0                 0                 0                 0  
Patient withdrew consent                 4                 2                 4                 3                 4                 4                 3                 2                 4  
Lost to Follow-up                 0                 2                 4                 1                 2                 2                 0                 3                 1  
Administrative problems                 0                 0                 0                 0                 0                 0                 1                 0                 0  
Protocol deviation                 5                 3                 1                 2                 3                 1                 2                 2                 3  
Discont. single-blind, Mis- randomized                 0                 1                 0                 0                 0                 0                 2                 0                 0  
[1] One pt. was mis-randomized, so discontinued from single-blind and was untreated in the double-blind.
[2] 2 pts. were mis-randomized, so discontinued from single-blind and were untreated in double-blind.



  Baseline Characteristics
  Hide Baseline Characteristics

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.
No text entered.

Reporting Groups
  Description
Placebo Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; for this arm all the 5 pills taken were placebos.
Aliskiren 150 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Aliskiren 300 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Amlodipine 5 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Amlodipine 10 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos. Amlodipine 10 mg arm starts with 1 week of Amlodipine 5 mg, then force titrated to 10 mg.
Aliskiren/Amlodipine 150/5 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Aliskiren/Amlodipine 150/10 mg 150/5 for 1 week, then up-titrated to 150/10 mg. Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Aliskiren/Amlodipine 300/5 mg Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Aliskiren/Amlodipine 300/10 mg Tablet 300/5 for 1 week, then up-titrated to 300/10 mg. Each dose was to be taken orally with water at approximately 8:00 A.M., except on the morning of the next office/clinic visit, when the study medication was to be taken at the site after the visit procedures were completed. In order to adequately blind the study, patients were required to take a total of 4 tablets and 1 capsule of study medication throughout the study; 4 of the 5 pills taken were placebos.
Total Total of all reporting groups

Baseline Measures
    Placebo     Aliskiren 150 mg     Aliskiren 300 mg     Amlodipine 5 mg     Amlodipine 10 mg     Aliskiren/Amlodipine 150/5 mg     Aliskiren/Amlodipine 150/10 mg     Aliskiren/Amlodipine 300/5 mg     Aliskiren/Amlodipine 300/10 mg Tablet     Total  
Number of Participants  
[units: participants]
  198     195     203     185     181     181     183     178     184     1688  
Age  
[units: years]
Mean ± Standard Deviation
  53.7  ± 10.32     54.3  ± 11.07     54.0  ± 9.99     54.2  ± 11.61     55.0  ± 10.34     53.9  ± 10.82     53.0  ± 10.59     54.8  ± 10.29     54.4  ± 10.86     54.1  ± 10.65  
Gender  
[units: participants]
                   
Female     108     76     108     86     94     84     96     100     78     830  
Male     90     119     95     99     87     97     87     78     106     858  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 150/5 mg vs. Aliskiren 150 mg on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

2.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 150/5 mg vs. Amlodipine 5 mg on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

3.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 150/5 mg vs. Placebo on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

4.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 150/10 mg vs. Aliskiren 150 mg on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

5.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 150/10 mg vs. Amlodipine 10 mg on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

6.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 150/10 mg vs. Placebo on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

7.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 300/5 mg vs. Aliskiren 300 mg on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

8.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 300/5 mg vs. Amlodipine 5 mg on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

9.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 300/5 mg vs. Placebo on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

10.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 300/10 mg vs. Aliskiren 300 mg on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

11.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 300/10 mg vs. Amlodipine 10 mg on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

12.  Primary:   Pairwise Comparison of Aliskiren/Amlodipine 300/10 mg vs. Placebo on Change in Mean Sitting Diastolic Blood Pressure (msDBP)   [ Time Frame: Baseline to end of study (Week 8) ]

13.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 150/5 mg vs. Aliskiren 150 mg on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

14.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 150/5 mg vs. Amlodipine 5 mg on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

15.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 150/5 mg vs. Placebo on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

16.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 150/10 mg vs. Aliskiren 150 mg on Change in Mean Sitting Systolic Blood Pressure (mssBP)   [ Time Frame: Baseline to end of study (Week 8) ]

17.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 150/10 mg vs. Amlodipine 10 mg on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

18.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 150/10 mg vs. Placebo on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

19.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 300/5 mg vs. Aliskiren 300 mg on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

20.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 300/5 mg vs. Amlodipine 5 mg on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

21.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 300/5 mg vs. Placebo on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

22.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 300/10 mg vs. Aliskiren 300 mg on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

23.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 300/10 mg vs. Amlodipine 10 mg on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

24.  Secondary:   Pairwise Comparison of Aliskiren/Amlodipine 300/10 mg vs. Placebo on Change in Mean Sitting Systolic Blood Pressure (msSBP)   [ Time Frame: Baseline to end of study (Week 8) ]

25.  Secondary:   Percentage of Patients With Blood Pressure Control (msSBP < 140 mm Hg and msDBP < 90 mm Hg) at End of Study   [ Time Frame: End of study (Week 8) ]

26.  Secondary:   Percentage of Patients Achieving a Successful Diastolic Blood Pressure Response   [ Time Frame: End of study (Week 8) ]

27.  Secondary:   Percentage of Patients Achieving a Successful Systolic Blood Pressure Response   [ Time Frame: End of study (Week 8) ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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
No text entered.  


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


No publications provided


Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00739973     History of Changes
Other Study ID Numbers: CSPA100A2305
Study First Received: August 20, 2008
Results First Received: January 13, 2011
Last Updated: June 2, 2011
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Canada: Health Canada
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
Greece: National Organization of Medicines
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Italy: National Institute of Health
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
South Africa: Medicines Control Council
Taiwan: Department of Health
United States: Food and Drug Administration
Dominican Republic: Consejo Nacional de Bioetica en Salud
Panama: Commemorative Institute GORGAS of Studies of Health
Mexico: National Institute of Public Health, Health Secretariat
Romania: National Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration