Study to Evaluate the Efficacy and Safety of Combination Aliskiren/Amlodipine in Patients Not Adequately Responding to Aliskiren Alone

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of combination aliskiren/amlodipine in patients not adequately controlled with aliskiren alone

Official Title
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A Randomized, Eight-week Double-blind, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Aliskiren / Amlodipine (300/5 mg and 300/10 mg) in Comparison With Aliskiren 300 mg in Patients With Essential Hypertension Not Adequately Responsive to Aliskiren 300 mg Monotherapy

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren 300 mg
* Drug: Aliskiren/Amlodipine 300/5 mg
* Drug: Aliskiren/Amlodipine 300/10 mg
* Drug: Placebo to Aliskiren
* Drug: Placebo to Aliskiren/Amlodipine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed patients or patients who have not been treated for hypertension within the 4 weeks prior to Visit 1 must have a mean sitting Diastolic Blood Pressure (msDBP) ≥ 95 mmHg and < 110 mmHg at Visits 1 and 2 Patients who have been treated for hypertension within the 4 weeks prior to - Visit 1 must have a msDBP ≥ 90 mmHg and < 110 mmHg at Visit 2 All patients must have a msDBP ≥ 90 mmHg and < 110 mmHg at Visit 4 Exclusion Criteria: Severe hypertension Pregnant or nursing (lactating) women Women of child-bearing potential Previous or current diagnosis of heart failure New York Heart Association (NYHA Class II-IV) Serum potassium ≥ 5.3 mEq/L (mmol/L) at Visit 1 Uncontrolled Type 1 or Type 2 diabetes mellitus Hypersensitivity to renin inhibitors, calcium channel blockers, or to drugs with Similar chemical structures History of hypertensive encephalopathy or cerebrovascular accident, or history of transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren 300 mg/Amlodipine 5 mg<br>Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks. | Drug: Aliskiren/Amlodipine 300/5 mg<br>* Aliskiren/Amlodipine 300/5 mg tablet taken orally once a day with a glass of water.<br>Drug: Placebo to Aliskiren<br>* Placebo to Aliskiren tablet taken orally once a day.<br>|
| Experimental: Aliskiren 300 mg/Amlodipine 10 mg<br>Participants received 1 Aliskiren/Amlodipine 300/10 mg tablet + 1 Placebo to Aliskiren tablet orally once daily in the morning for 8 weeks. | Drug: Aliskiren/Amlodipine 300/10 mg<br>* Aliskiren/Amlodipine 300/10 mg taken orally once a day with a glass of water.<br>Drug: Placebo to Aliskiren<br>* Placebo to Aliskiren tablet taken orally once a day.<br>|
| Active Comparator: Aliskiren 300 mg<br>Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks. | Drug: Aliskiren 300 mg<br>* Aliskiren 300 mg tablet taken orally once a day with a glass of water.<br>Drug: Placebo to Aliskiren/Amlodipine<br>* Placebo to Aliskiren/Amlodipine taken orally once a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Study in the Mean Sitting Diastolic Blood Pressure (msDBP) | After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msDBP at baseline from the msDBP at 8 weeks was calculated using an Analysis of Covariance (ANCOVA) model with baseline as a covariate and treatment and region as two factors. | Baseline, End of Study (Week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of Study in the Mean Sitting Systolic Blood Pressure (msSBP) | After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msSBP at baseline from the msSBP at 8 weeks was calculated using an ANCOVA model with baseline as a covariate and treatment and region as two factors. | Baseline, End of Study (Week 8) | 
| Number of Participants With Serious Adverse Events and Adverse Events | The number of participants with any Serious Adverse Event and the number of participants with Adverse Events in any system organ class. Additional information about Adverse Events can be found in the Adverse Event Section. | 8 weeks | 
| Percentage of Participants Achieving Blood Pressure Control | After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. Blood Pressure control was defined as having a mean sitting Diastolic Blood Pressure <90 and a mean sitting Systolic Blood Pressure <140. | 8 weeks | 
| Percentage of Participants Achieving a Diastolic Blood Pressure Response | After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A Diastolic Blood Pressure Response was defined as a mean sitting Diastolic Blood Pressure (msDBP) <90 mmHg or a ≥ 10 mmHg reduction in msDBP from baseline. | 8 weeks | 
| Percentage of Participants Achieving a Systolic Blood Pressure Response | After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A Systolic Blood Pressure Response was defined as a mean sitting Systolic Blood Pressure (msSBP) <140 mmHg or a ≥ 20 mmHg reduction in msSBP from baseline. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aliskiren, Amlodipine, Non-responder to aliskiren