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

• ClinicalTrials.gov Identifier: NCT00834041
• Recruitment Status: Completed
• First Posted: February 3, 2009
• Results First Posted: May 9, 2011
• Last Update Posted: May 9, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: Aliskiren 3.125 mini-tablets	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: April 2009
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: January 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

1. Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 9 [ Time Frame: 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.
2. 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 [ Time Frame: 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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Kentucky

Investigative Site

Louisville, Kentucky, United States

Belgium

Investigative Site

Brussels, Belgium

Brazil

Investigative Site

Brasilia, Brazil

Hungary

Investigative Site

Budapest, Hungary

Poland

Investigative Site

Warsaw, Poland

Sponsors and Collaborators

Novartis

Investigators

• Study Chair: Novartis; Novartis

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: External Affairs, Novartis
• ClinicalTrials.gov Identifier: NCT00834041
• Other Study ID Numbers: CSPP100A2256
• First Posted: February 3, 2009
• Results First Posted: May 9, 2011
• Last Update Posted: May 9, 2011
• Last Verified: April 2011

Keywords provided by Novartis:

aliskiren; pediatric; hypertension; pharmacokinetics (PK); pharmacodynamics (PD); plasma renin activity; mini-tablet formulation

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases