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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00834041
First received: January 30, 2009
Last updated: April 15, 2011
Last verified: April 2011
  Purpose

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 Intervention Phase
Hypertension
Drug: Aliskiren 3.125 mini-tablets
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Apparent Plasma Clearance (CL/F) at Day 8 in 6-11 and 12-17 Year Old Patients [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 39
Study Start Date: April 2009
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00834041

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

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00834041     History of Changes
Other Study ID Numbers: CSPP100A2256
Study First Received: January 30, 2009
Results First Received: January 18, 2011
Last Updated: April 15, 2011
Health Authority: United States: Food and Drug Administration
Hungary: National Institute of Pharmacy
Brazil: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

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

ClinicalTrials.gov processed this record on July 29, 2014