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

Phase 3

Completed

Brief Summary: 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Aliskiren	Aliskiren	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
Enalapril	Enalapril	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

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at to End of Study	Baseline - end of study (Week 52 or Last observation carried forward (LOCF)	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.

Secondary Outcome Measures

Name	Time	Method
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study	Baseline - end of study (Week 52 or Last observation carried forward (LOCF)	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.
Change in Mean Arterial Pressure (MAP) (mmHg) From Baseline to End of Study	Baseline to end of study (Week 52 or LOCF)	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).