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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00834041
• Other study ID #: CSPP100A2256
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 30, 2009
• Last updated: April 15, 2011
• Start date: April 2009
• Est. completion date: January 2010

Study information

• Verified date: April 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationHungary: National Institute of PharmacyBrazil: Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

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

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Aliskiren 3.125 mini-tablets
Oral mini-tablets (3.125 mg) of aliskiren once each morning

Locations

Country	Name	City	State
Belgium	Investigative Site	Brussels
Brazil	Investigative Site	Brasilia
Hungary	Investigative Site	Budapest
Poland	Investigative Site	Warsaw
United States	Investigative Site	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Area Under the Plasma Concentration-time Curve (AUC0-t) 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	No
Primary	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	No
Secondary	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	No
Secondary	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)	No