A Study to Evaluate the Safety/Tolerability and Pharmacokinetics of Aliskiren in Hypertensive Pediatric and Adolescent Patients 6-17 Years of Age

Study Overview
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Brief Summary
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This first open-label study in a pediatric population was designed to evaluate aliskiren safety and pharmacokinetics after single and multiple dosing in 6-17 year old children with hypertension.

Official Title
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An 8-day Open-label, Multiple-dose, Multicenter Study to Evaluate the Safety/Tolerability and Pharmacokinetics of Aliskiren in Hypertensive Pediatric and Adolescent Patients 6-17 Years of Age

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Aliskiren 3.125 mini-tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 6-17 years of age Documented history of hypertension as defined in National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) Must be ≥ 21.0 kg and ≤ 100.0 kg at randomization Able to safely wash out previous antihypertensive therapy for 1-2 weeks Exclusion Criteria: Body weight of < 21 kg (45 lbs) or > 100 kg (220 lbs) Inability to discontinue prior antihypertensive medication as required during the washout period Any clinically significant abnormalities or clinically noteworthy abnormal laboratory values Renal artery stenosis Current diagnosis of heart failure (NYHA Class II-IV) msSBP ≥ 25% above the 95th percentile for age, gender, and height at Visit 2 Second or third degree heart block with or without a pacemaker Atrial fibrillation or atrial flutter at Visit 1, or potentially life threatening or any symptomatic arrhythmia during the 12 months prior to Visit 1 Evidence of current symptomatic valvular disease Other protocol-defined inclusion/exclusion criteria applied to the study.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aliskiren 2 mg/kg<br>Oral mini-tablets (3.125 mg) of aliskiren dosed at 2 mg/kg body weight once each morning | Drug: Aliskiren 3.125 mini-tablets<br>* Oral mini-tablets (3.125 mg) of aliskiren once each morning<br>|
| Experimental: Aliskiren 6 mg/kg<br>Oral mini-tablets (3.125 mg) of aliskiren dosed at 6 mg/kg body weight once each morning | Drug: Aliskiren 3.125 mini-tablets<br>* Oral mini-tablets (3.125 mg) of aliskiren once each morning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients | Blood samples (1 mL) for pharmacokinetic (PK) evaluation were drawn pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 10, and 24 hours following administration of aliskiren on Day 1 and Day 8. The pre-dose PK evaluations were collected in a fasted state (7-12 hours without food or beverage except water). PK parameters were calculated from plasma concentration-time data and actual recorded sampling times for each patient, using non-compartmental methods with the software program WinNonlin Pro v5.2. | Day 1 and Day 8 | 
| Area Under the Plasma Concentration-time Curve (AUC0-τ) in One Dosing Interval (24 h) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients | Blood samples (1 mL) for pharmacokinetic (PK) evaluation were drawn pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 10, and 24 hours following administration of aliskiren on Day 1 and Day 8. The pre-dose PK evaluations were collected in a fasted state (7-12 hours without food or beverage except water). PK parameters were calculated from plasma concentration-time data and actual recorded sampling times for each patient, using non-compartmental methods with the software program WinNonlin Pro v5.2. | Day 1 and Day 8 | 
| Apparent Plasma Clearance (CL/F) at Day 8 in 6-11 and 12-17 Year Old Patients | Blood samples (1 mL) for pharmacokinetic (PK) evaluation were drawn pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 10, and 24 hours following administration of aliskiren on Day 1 and Day 8. The pre-dose PK evaluations were collected in a fasted state (7-12 hours without food or beverage except water). PK parameters were calculated from plasma concentration-time data and actual recorded sampling times for each patient, using non-compartmental methods with the software program WinNonlin Pro v5.2. | Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9 | Blood samples (2 mL) for pharmacodynamics evaluation of plasma renin activity were drawn pre-dose and at 2 and 10 hours following the dose of study medication on Day 1 and at pre-dose and at 2, 10, and 24 hours post-dose on Day 8-9. | Baseline to 2 and 10 hours post-dose on Day 1; pre-dose, 2, 10, and 24 hours post-dose on Day 8-9 | 
| Change in Mean Sitting Systolic and Diastolic Blood Pressure (msSBP and msDBP) From Baseline to the End of Treatment (Day 9) in 6-11 and 12-17 Year Old Patients | Blood pressure (BP) measurements were made with a mercury sphygmomanometer or an automated blood pressure measuring device. Sitting BP was measured 3 times at 2-3 minute intervals after the patient had been sitting for 5 minutes. Means of the 3 measurements were calculated. A negative change in BP indicates lowered BP. | Baseline to end of treatment (Day 9) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aliskiren, pediatric, hypertension, pharmacokinetics (PK), pharmacodynamics (PD), plasma renin activity, mini-tablet formulation