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

NCT00834041 | Completed Phase 1 Results

• 1 other identifier: CSPP100A2256
• Study Type: interventional
• Target: 39
• Locations: 5 countries
• Sites: 5

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.

Conditions

Hypertension

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Change in Plasma Renin Activity From Baseline on Day 1, Day 8, and Day 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

  Baseline to end of treatment (Day 9)

Study Arms (2)

Aliskiren 2 mg/kg

EXPERIMENTAL

Oral mini-tablets (3.125 mg) of aliskiren dosed at 2 mg/kg body weight once each morning

Drug: Aliskiren 3.125 mini-tablets

Aliskiren 6 mg/kg

EXPERIMENTAL

Oral mini-tablets (3.125 mg) of aliskiren dosed at 6 mg/kg body weight once each morning

Drug: Aliskiren 3.125 mini-tablets

Interventions

Aliskiren 3.125 mini-tablets DRUG

Oral mini-tablets (3.125 mg) of aliskiren once each morning

Aliskiren 2 mg/kg; Aliskiren 6 mg/kg

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (5)

Investigative Site

Louisville, Kentucky, United States

Location

Investigative Site

Brussels, Belgium

Location

Investigative Site

Brasília, Brazil

Location

Investigative Site

Budapest, Hungary

Location

Investigative Site

Warsaw, Poland

Location

Related Publications (1)

• 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.

  PMID: 23610239 DERIVED

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis

  Novartis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 30, 2009
• First Posted: February 3, 2009
• Study Start: April 1, 2009
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: May 9, 2011
• Results First Posted: May 9, 2011

Record last verified: 2011-04

Locations

BR (1); US (1); BE (1); HU (1); PL (1)