Clinical trial NCT00834041: A Study to Evaluate the Safety/Tolerability and Pharmacokinetics of Aliskiren in Hypertensive Pediatric and Adolescent Patients 6-17 Years of Age
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hypertension
Keywords: aliskiren
pediatric
hypertension
pharmacokinetics (PK)
pharmacodynamics (PD)
plasma renin activity
mini-tablet formulation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-02-03
Enrollment: 39
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) at Day 1 and Day 8 in 6-11 and 12-17 Year Old Patients
timeFrame: Day 1 and Day 8
measure: 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
timeFrame: Day 1 and Day 8
measure: Apparent Plasma Clearance (CL/F) at Day 8 in 6-11 and 12-17 Year Old Patients
timeFrame: Day 8
Secondary outcomes:
measure: Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9
timeFrame: Baseline to 2 and 10 hours post-dose on Day 1; pre-dose, 2, 10, and 24 hours post-dose on Day 8-9
measure: 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
timeFrame: Baseline to end of treatment (Day 9)
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Investigative Site
state: Kentucky
city: Brussels
country: Belgium
facility: Investigative Site
city: Brasilia
country: Brazil
facility: Investigative Site
city: Budapest
country: Hungary
facility: Investigative Site
city: Warsaw
country: Poland
facility: Investigative Site
Study officials:
affiliation: Novartis
name: Novartis
role: STUDY_CHAIR
References:
citation: 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.