Efficacy and Safety of SPA100 (Fixed-dose Combination of Aliskiren/Amlodipine) in Patients With Essential Hypertension

Study Overview
=================
Brief Summary
-----------------
The purpose of the study was to evaluate the efficacy (blood pressure lowering effect) and safety of SPA100 (Fixed-dose Combination of Aliskiren and Amlodipine) in patients with essential hypertension (mean sitting diastolic blood pressure [msDBP] ≥ 95 mmHg and < 110 mmHg and mean sitting systolic blood pressure [msSBP] ≥ 140 mmHg ). This study was conducted to support registration of the fixed-dose combination of aliskiren and amlodipine for the treatment of hypertension in Japan.

Official Title
-----------------
An 8-week Double-blind, Multicenter, Randomized, 6-arm, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of SPA100 (Fixed-dose Combination of Aliskiren and Amlodipine) in Patients With Essential Hypertension

Conditions
-----------------
Essential Hypertension

Intervention / Treatment
-----------------
* Drug: Aliskiren/Amlodipine 150/2.5 mg
* Drug: Aliskiren/amlodipine 150/5 mg
* Drug: Aliskiren 150 mg
* Drug: Amlodipine 2.5 mg
* Drug: Placebo of Aliskiren
* Drug: Placebo of Amlodipine
* Drug: Placebo of Aliskiren/amlodipine 150/2.5 mg
* Drug: Placebo of Aliskiren/amlodipine 150/5 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with essential hypertension (msDBP ≥ 95 mmHg and < 110 mmHg and msSBP ≥140 mmHg ) Outpatients Exclusion Criteria: Severe hypertension (msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg) History of allergy or hypersensitivity to renin inhibitors, calcium channel blockers History or evidence of a secondary hypertension Other protocol-defined inclusion/exclusion criteria applied

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. In single blind run-in (4 weeks) and double blind treatment period (8 weeks), patients were received matching placebo of aliskiren/amlodipine 150/5 mg tablet, aliskiren/amlodipine 150/2.5 mg tablet, aliskiren 150 mg tablet and two amlodipine 2.5 mg capsules once daily. | Drug: Placebo of Aliskiren<br>* Aliskiren placebo tablet<br>Drug: Placebo of Amlodipine<br>* Amlodipine placebo capsule<br>Drug: Placebo of Aliskiren/amlodipine 150/2.5 mg<br>* Aliskiren/amlodipine 150/2.5 mg placebo tablet<br>Drug: Placebo of Aliskiren/amlodipine 150/5 mg<br>* Aliskiren/amlodipine 150/5 mg placebo tablet<br>|
| Active Comparator: Aliskiren 150 mg<br>In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Aliskiren 150 mg tablet once daily (o.d)+ placebo of two amlodipine 2.5 mg capsule o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period. | Drug: Aliskiren 150 mg<br>* Aliskiren 150 mg tablet<br>Drug: Placebo of Amlodipine<br>* Amlodipine placebo capsule<br>Drug: Placebo of Aliskiren/amlodipine 150/2.5 mg<br>* Aliskiren/amlodipine 150/2.5 mg placebo tablet<br>Drug: Placebo of Aliskiren/amlodipine 150/5 mg<br>* Aliskiren/amlodipine 150/5 mg placebo tablet<br>|
| Active Comparator: Amlodipine 2.5 mg<br>In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received Amlodipine 2.5 mg capsule once daily (o.d)+ placebo of amlodipine 2.5 mg capsule o.d., Aliskiren 150 mg o.d., aliskiren/amlodipine 150/5 mg tablet o.d , aliskiren/amlodipine 150/2.5 mg tablet o.d for 8 weeks of double blind period. | Drug: Amlodipine 2.5 mg<br>* Amlodipine 2.5 mg capsule<br>Drug: Placebo of Aliskiren<br>* Aliskiren placebo tablet<br>Drug: Placebo of Amlodipine<br>* Amlodipine placebo capsule<br>Drug: Placebo of Aliskiren/amlodipine 150/2.5 mg<br>* Aliskiren/amlodipine 150/2.5 mg placebo tablet<br>Drug: Placebo of Aliskiren/amlodipine 150/5 mg<br>* Aliskiren/amlodipine 150/5 mg placebo tablet<br>|
| Active Comparator: Amlodipine 5 mg<br>In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received amlodipine 5 mg (two amlodipine 2.5 mg capsules o.d.)+ placebo of aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. , aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period. | Drug: Amlodipine 2.5 mg<br>* Amlodipine 2.5 mg capsule<br>Drug: Placebo of Aliskiren<br>* Aliskiren placebo tablet<br>Drug: Placebo of Aliskiren/amlodipine 150/2.5 mg<br>* Aliskiren/amlodipine 150/2.5 mg placebo tablet<br>Drug: Placebo of Aliskiren/amlodipine 150/5 mg<br>* Aliskiren/amlodipine 150/5 mg placebo tablet<br>|
| Experimental: Aliskiren/amlodipine 150/2.5 mg<br>In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/2.5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/5 mg tablet o.d. for 8 weeks of double blind period. | Drug: Aliskiren/Amlodipine 150/2.5 mg<br>* Aliskiren/amlodipine 150/2.5 mg tablet<br>Drug: Placebo of Aliskiren<br>* Aliskiren placebo tablet<br>Drug: Placebo of Amlodipine<br>* Amlodipine placebo capsule<br>Drug: Placebo of Aliskiren/amlodipine 150/5 mg<br>* Aliskiren/amlodipine 150/5 mg placebo tablet<br>|
| Experimental: Aliskiren/amlodipine 150/5 mg<br>In order to adequately blind the study, patients were required to take a total of 3 tablets and 2 capsules of study medication throughout the study. Patients received aliskiren/amlodipine 150/5 mg tablet o.d. + placebo of two amlodipine 2.5 mg capsules o.d., aliskiren 150 mg tablet o.d., aliskiren/amlodipine 150/2.5 mg tablet o.d. for 8 weeks of double blind period. | Drug: Aliskiren/amlodipine 150/5 mg<br>* Aliskiren/amlodipine 150/5 mg tablet<br>Drug: Placebo of Aliskiren<br>* Aliskiren placebo tablet<br>Drug: Placebo of Amlodipine<br>* Amlodipine placebo capsule<br>Drug: Placebo of Aliskiren/amlodipine 150/2.5 mg<br>* Aliskiren/amlodipine 150/2.5 mg placebo tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) to End of Study (Week 8) | Sitting blood pressure was measured at trough (24 hours ± 2 hours post dose) and recorded at all study visits. At the first study visit, blood pressure was measured in both arms and the arm with highest sitting DBP was found and used for all subsequent readings throughout the study. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these three sitting blood pressure measurements were used as the average sitting blood pressure for that visit. Analysis of covariance (ANCOVA) model contained treatment and region as two factors and baseline as a covariate. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) to End of Study (Week 8) | Sitting blood pressure was measured at trough (24 hours ± 2 hours post dose) and recorded at all study visits. At the first study visit, blood pressure was measured in both arms and the arm with highest sitting DBP was found and used for all subsequent readings throughout the study. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these three sitting blood pressure measurements were used as the average sitting blood pressure for that visit. Analysis of covariance (ANCOVA) model contained treatment and region as two factors and baseline as a covariate. | Baseline, Week 8 | 
| Percentage of Participants Achieving Blood Pressure Control at Endpoint | Blood pressure control is defined as having as a msDBP < 90 mmHg and a msSBP < 140 mmHg. | 8 weeks | 
| Percentage of Participants Achieving a Successful Response Rate | The response rate was defined as percentage of participants who achieved msDBP < 90 mmHg or its reduction ≥ 10 mmHg from baseline to endpoint. | 8 weeks | 
| Number of Participants With Adverse Events, Serious Adverse Events and Death | Number of patients with adverse events regardless of study drug relationship during the double-blind treatment period were reported. Serious adverse events of double blind period were reported. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aliskiren, Amlodipine, Essential hypertension