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

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

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 Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Aliskiren 3.125 mini-tablets

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Investigative Site
• Brazil
  • Brasilia, Brazil
    • Investigative Site
• Hungary
  • Budapest, Hungary
    • Investigative Site
• Poland
  • Warsaw, Poland
    • Investigative Site
• United States
  • Kentucky
    • Louisville, Kentucky, United States
      • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Sullivan JE, Keefe D, Zhou Y, Satlin L, Fang H, Yan JH. Pharmacokinetics, safety profile, and efficacy of aliskiren in pediatric patients with hypertension. Clin Pediatr (Phila). 2013 Jul;52(7):599-607. doi: 10.1177/0009922813483875. Epub 2013 Apr 22.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: January 30, 2009
• First Submitted That Met QC Criteria: February 2, 2009
• First Posted (Estimate): February 3, 2009

Study Record Updates

• Last Update Posted (Estimate): May 9, 2011
• Last Update Submitted That Met QC Criteria: April 15, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: pediatric; hypertension; pharmacokinetics (PK); aliskiren; plasma renin activity; pharmacodynamics (PD); mini-tablet formulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CSPP100A2256