NCT00834041 - A Study to Evaluate the Safety/Tolerability and Pharmacokinetics of Aliskiren in Hypertensive Pediatric and Adolescent Patients 6-17 Years of Age | Crick

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

39

Conditions

Hypertension

Interventions

Aliskiren 3.125 mini-tabletsDRUG

Oral mini-tablets (3.125 mg) of aliskiren once each morning

Eligibility

Sex: ALLMin age: 6 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (5)

Investigative Site

Louisville, Kentucky, United States

Investigative Site

Brussels, Belgium

Investigative Site

Brasília, Brazil

Investigative Site

Budapest, Hungary

Investigative Site

Warsaw, Poland

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Day 8

Secondary Outcomes

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.