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

Phase 1

Completed

Conditions: Hypertension

Interventions: Drug: Aliskiren 3.125 mini-tablets

Registration Number: NCT00834041

Lead Sponsor: Novartis

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 39

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aliskiren 2 mg/kg	Aliskiren 3.125 mini-tablets	Oral mini-tablets (3.125 mg) of aliskiren dosed at 2 mg/kg body weight once each morning
Aliskiren 6 mg/kg	Aliskiren 3.125 mini-tablets	Oral mini-tablets (3.125 mg) of aliskiren dosed at 6 mg/kg body weight once each morning

Primary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients	Day 1 and Day 8	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.
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	Day 1 and Day 8	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.
Apparent Plasma Clearance (CL/F) at Day 8 in 6-11 and 12-17 Year Old Patients	Day 8	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.

Secondary Outcome Measures

Name	Time	Method
Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 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	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.
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	Baseline to end of treatment (Day 9)	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.