An Extension Study to Evaluate the Long Term Safety, Tolerability and Efficacy of Aliskiren Compared to Enalapril in Pediatric Hypertensive Patients 6-17 Years of Age

A Multicenter, Double-blind, Randomized, 52-week, Extension Study to Evaluate the Long Term Safety, Tolerability and Efficacy of Aliskiren Compared to Enalapril in Pediatric Hypertensive Patients 6-17 Years of Age

The purpose of this study is to evaluate in a randomized, double-blind fashion, the long-term safety, tolerability and efficacy profile of aliskiren compared to the active comparator enalapril in children, 6 - 17 years old with hypertension (msSBP ≥ 95th percentile for age, gender and height, at baseline in study CSPP100A2365). Patients will be randomized to receive either aliskiren or enalapril. Weight-group based doses of aliskiren or enalapril will be administered once daily and children will receive study medication in a double-blind manner. This study is being conducted to support monotherapy registration of aliskiren for the treatment of hypertension in pediatric patients 6-17 years of age (age at baseline in Study CSPP100A2365).

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Aliskiren; Drug: Enalapril

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 3

Contacts and Locations

Study Locations

• Guatemala
  • Guatemala City, Guatemala, 01010
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1083
    • Novartis Investigative Site
  • Budapest, Hungary, 1131
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Miskolc, Hungary, 3529
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary, 4400
    • Novartis Investigative Site
  • Szeged, Hungary, 6725
    • Novartis Investigative Site
  • Veszprem, Hungary, H-8200
    • Novartis Investigative Site
• Poland
  • Warszawa, Poland, 04-154
    • Novartis Investigative Site
• Puerto Rico
  • San Juan, Puerto Rico, 00907
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 85107
    • Novartis Investigative Site
  • Bratislava, Slovakia, 84103
    • Novartis Investigative Site
  • Martin, Slovakia, 03601
    • Novartis Investigative Site
  • Myjava, Slovakia, 90701
    • Novartis Investigative Site
  • Presov, Slovakia, 08001
    • Novartis Investigative Site
  • Trnava, Slovakia, 91701
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Ankara, Turkey, 06500
    • Novartis Investigative Site
  • Ankara, Turkey, 06490
    • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0006
      • Novartis Investigative Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Novartis Investigative Site
  • California
    • Los Angeles, California, United States, 90048
      • Novartis Investigative Site
  • Georgia
    • Dalton, Georgia, United States, 30721
      • Novartis Investigative Site
  • Idaho
    • Lewiston, Idaho, United States, 83501
      • Novartis Investigative Site
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Novartis Investigative Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Novartis Investigative Site
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Novartis Investigative Site
    • Jackson, Mississippi, United States, 39209
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10016
      • Novartis Investigative Site
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Novartis Investigative Site
    • Toledo, Ohio, United States, 43606
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • Novartis Investigative Site
    • Portland, Oregon, United States, 07227
      • Novartis Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Novartis Investigative Site
  • Texas
    • Amarillo, Texas, United States, 79106
      • Novartis Investigative Site
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• msSBP (mean of 3 systolic blood pressure measurements) must be ≥ 95th percentile for age, gender and height, at Visit 2 (randomization), in study CSPP100A2365
• Must be ≥ 20 kg and ≤ 150 kg at Visit 2 (randomization), in study CSPP100A2365
• Must be able to swallow minitablets (2mm in diameter) administered in soft food
• Successful completion of Phase 1 (dose response phase) and at least 1 week of Phase 2 (placebo withdrawal phase) of the CSPP100A2365 protocol, with no serious drug-related adverse event(s).

Exclusion Criteria:

• Patient receiving immunosuppressant medication (e.g. cyclosporine, MMF, etc) other than oral/topical steroids, for any medical condition
• Current diagnosis of heart failure (NYHA Class II-IV) or history of cardiomyopathy or obstructive valvular disease
• msSBP ≥ 25% above the 95th percentile
• Second or third degree heart block without a pacemaker
• AST/SGOT or ALT/SGPT >3 times the upper limit of the reference range
• Total bilirubin > 2 times the upper limit of the reference range
• Creatinine clearance < 30 mL/min/1.73m² (calculated using Modified Schwartz formula to estimate glomerular filtration rate [GFR]), based on the serum creatinine concentration obtained at the screening visit)
• WBC count < 3000/mm³
• Platelet count < 100,000/mm³
• Serum potassium > 5.2 mEq/L
• Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aliskiren; Patients will receive one of the following doses based on the their weight: Low weight (≥20 to <50 kg) patients: Starting dose 37.5 mg with optional titration to 75 and then 150 mg Mid weight (≥50 to <80 kg) patients: Starting dose 75 mg with optional titration to 150 and then 300 mg High weight (≥80 to ≤150 kg) patients: Starting dose 150 mg with optional titration to 300 and then 600 mg	Drug: Aliskiren; Low weight patients: Starting dose 37.5 mg with optional titration to 75 and then 150 mg Mid weight patients: Starting dose 75 mg with optional titration to 150 and then 300 mg High weight patients: Starting dose 150 mg with optional titration to 300 and then 600 mg
Active Comparator: Enalapril; Patients will receive one of the following doses based on their weight: Low weight (≥20 to <50 kg) patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight (≥50 to <80 kg) patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight (≥80 to ≤150 kg) patients: Starting dose 10 mg with optional titration to 20 and then 40 mg	Drug: Enalapril; Low weight patients: Starting dose 2.5 mg with optional titration to 5 and then 10 mg Mid weight patients: Starting dose 5 mg with optional titration to 10 and then 20 mg High weight patients: Starting dose 10 mg with optional titration to 20 and then 40 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at to End of Study	Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sSBP measurements were used as the average sitting office blood pressure for that visit.	Baseline - end of study (Week 52 or Last observation carried forward (LOCF)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study	Sitting blood pressure was measured using a calibrated standard sphygmomanometer after the participants remained in sitting position for 5 minutes at clinic during the visit. The repeat sitting measurements were made at 2 to 3 minute intervals and the mean of three sDBP measurements were used as the average sitting office blood pressure for that visit.	Baseline - end of study (Week 52 or Last observation carried forward (LOCF)
Change in Mean Arterial Pressure (MAP) (mmHg) From Baseline to End of Study	MAP was defined as the average arterial pressure during a single cardiac cycle. The MAP was measured as sum of diastolic blood pressure (DBP) and one third of difference between systolic blood pressure (SBP) and DBP i.e. MAP = DBP+1/3*(SBP--DBP).	Baseline to end of study (Week 52 or LOCF)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Wang GM, Li LJ, Tang WL, Wright JM. Renin inhibitors versus angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database Syst Rev. 2020 Oct 22;10(10):CD012569. doi: 10.1002/14651858.CD012569.pub2.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: June 23, 2010
• First Submitted That Met QC Criteria: June 25, 2010
• First Posted (Estimate): June 28, 2010

Study Record Updates

• Last Update Posted (Estimate): March 7, 2016
• Last Update Submitted That Met QC Criteria: February 8, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: hypertension; secondary; Pediatric hypertension; primary hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Enalapril
• Other Study ID Numbers: CSPP100A2365E1; 2009-017029-20 (EudraCT Number)