An Extension Study to Evaluate the Long Term Safety, Tolerability and Efficacy of Aliskiren Compared to Enalapril in Pediatric Hypertensive Patients 6-17 Years of Age

Study Overview
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Brief Summary
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The purpose of this study is to evaluate in a randomized, double-blind fashion, the long-term safety, tolerability and efficacy profile of aliskiren compared to the active comparator enalapril in children, 6 - 17 years old with hypertension (msSBP ≥ 95th percentile for age, gender and height, at baseline in study CSPP100A2365). Patients will be randomized to receive either aliskiren or enalapril. Weight-group based doses of aliskiren or enalapril will be administered once daily and children will receive study medication in a double-blind manner. This study is being conducted to support monotherapy registration of aliskiren for the treatment of hypertension in pediatric patients 6-17 years of age (age at baseline in Study CSPP100A2365).

Official Title
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A Multicenter, Double-blind, Randomized, 52-week, Extension Study to Evaluate the Long Term Safety, Tolerability and Efficacy of Aliskiren Compared to Enalapril in Pediatric Hypertensive Patients 6-17 Years of Age

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren
* Drug: Enalapril


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: msSBP (mean of 3 systolic blood pressure measurements) must be ≥ 95th percentile for age, gender and height, at Visit 2 (randomization), in study CSPP100A2365 Must be ≥ 20 kg and ≤ 150 kg at Visit 2 (randomization), in study CSPP100A2365 Must be able to swallow minitablets (2mm in diameter) administered in soft food Successful completion of Phase 1 (dose response phase) and at least 1 week of Phase 2 (placebo withdrawal phase) of the CSPP100A2365 protocol, with no serious drug-related adverse event(s). Exclusion Criteria: Patient receiving immunosuppressant medication (e.g. cyclosporine, MMF, etc) other than oral/topical steroids, for any medical condition Current diagnosis of heart failure (NYHA Class II-IV) or history of cardiomyopathy or obstructive valvular disease msSBP ≥ 25% above the 95th percentile Second or third degree heart block without a pacemaker AST/SGOT or ALT/SGPT >3 times the upper limit of the reference range Total bilirubin > 2 times the upper limit of the reference range Creatinine clearance < 30 mL/min/1.73m² (calculated using Modified Schwartz formula to estimate glomerular filtration rate [GFR]), based on the serum creatinine concentration obtained at the screening visit) WBC count < 3000/mm³ Platelet count < 100,000/mm³ Serum potassium > 5.2 mEq/L Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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<br>Patients will receive one of the following doses based on the their weight: Low weight (≥20 to <50 kg) patients: Starting dose 37.5 mg with optional titration to 75 and then 150 mg Mid weight (≥50 to <80 kg) patients: Starting dose 75 mg with optional titration to 150 and then 300 mg High weight (≥80 to ≤150 kg) patients: Starting dose 150 mg with optional titration to 300 and then 600 mg | Drug: Aliskiren<br>* Low weight patients: Starting dose 37.5 mg with optional titration to 75 and then 150 mg Mid weight patients: Starting dose 75 mg with optional titration to 150 and then 300 mg High weight patients: Starting dose 150 mg with optional titration to 300 and then 600 mg<br>|
| Active Comparator: Enalapril<br>Patients will receive one of the following doses based on their weight: Low weight (≥20 to <50 kg) patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight (≥50 to <80 kg) patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight (≥80 to ≤150 kg) patients: Starting dose 10 mg with optional titration to 20 and then 40 mg | Drug: Enalapril<br>* Low weight patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight patients: Starting dose 10 mg with optional titration to 20 and then 40 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at to End of Study | Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit. | Baseline - end of study (Week 52 or Last observation carried forward (LOCF) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study | Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sDBP measurements were used as the average sitting office blood pressure for that visit. | Baseline - end of study (Week 52 or Last observation carried forward (LOCF) | 
| Change in Mean Arterial Pressure (MAP) (mmHg) From Baseline to End of Study | MAP was defined as the average arterial pressure during a single cardiac cycle. The MAP was measured as sum of diastolic blood pressure (DBP) and one third of difference between systolic blood pressure (SBP) and DBP i.e. MAP = DBP+1/3*(SBP--DBP). | Baseline to end of study (Week 52 or LOCF) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric hypertension, primary hypertension, secondary, hypertension