Safety and Tolerability of Valsartan in Children 6 to 17 Years of Age

A Multicenter, Open-label, 18 Month Study to Evaluate the Long-term Safety and Tolerability of Valsartan in Children 6 to 17 Years of Age With Hypertension and With or Without Chronic Kidney Disease

The purpose of this study is to assess the long-term safety and tolerability profile of valsartan and valsartan-based treatments in children with hypertension, with or without chronic kidney disease.

Study Overview

• Status: Completed
• Conditions: Hypertension; Chronic Kidney Disease
• Intervention / Treatment: Drug: Valsartan; Drug: amlodipine; Drug: Hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Barranquilla, Colombia
    • Novartis Investigative Site
  • Cali, Colombia
    • Novartis Investigative Site
  • Santander
    • Bucaramanga, Santander, Colombia, 0001
      • Novartis Investigative Site
• Finland
  • Helsinki, Finland, 00029
    • Novartis Investigative Site
• Germany
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Cottbus, Germany, 03048
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Rostock, Germany, 18107
    • Novartis Investigative Site
• Guatemala
  • Guatemala City, Guatemala, 01010
    • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
• Philippines
  • Manila, Philippines, 1000
    • Novartis Investigative Site
  • Quezon City, Philippines, 1100
    • Novartis Investigative Site
  • Quezon City, Philippines, 1101
    • Novartis Investigative Site
• Poland
  • Warszawa, Poland, 04-154
    • Novartis Investigative Site
• Romania
  • Bucuresti, Romania, 20395
    • Novartis Investigative Site
  • Bucuresti, Romania, 041451
    • Novartis Investigative Site
  • Iasi, Romania, 700309
    • Novartis Investigative Site
  • Jud Cluj
    • Cluj-Napoca, Jud Cluj, Romania
      • Novartis Investigative Site
  • jud Mures
    • Tg. Mures, jud Mures, Romania, 540104
      • Novartis Investigative Site
  • jud. Timis
    • Timisoara, jud. Timis, Romania, 300011
      • Novartis Investigative Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119991
    • Novartis Investigative Site
  • Moscow, Russian Federation, 127412
    • Novartis Investigative Site
  • Moscow, Russian Federation, 125315
    • Novartis Investigative Site
  • Voronezh, Russian Federation, 394036
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 229899
    • 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:

• Documented diagnosis of hypertension
• able to swallow a tablet
• body weight ≥18 kg and ≤160 kg at baseline
• MSSBP must be ≥ 95th percentile and ≤25% above the 95th percentile for age, gender and height.

Exclusion Criteria:

• Any clinically significant physical abnormalities or clinically relevant abnormal laboratory values (other than those relating to renal function) obtained at the screening visit. Including the following:

  1. AST/SGOT or ALT/SGPT >3 times the upper limit of the reference range. Patients known to have active or chronic hepatitis were excluded.
  2. Total bilirubin >2 times the upper limit of the reference range
  3. Estimated GFR <30 mL/min/1.73m² (calculated using Modified Schwartz Formula)
  4. WBC count <3000/mm³
  5. Platelet count <100,000/mm³
  6. Serum potassium >5.3 mmol/L
  7. Hemoglobin <8 g/dL
• Uncontrolled diabetes mellitus
• Unilateral, bilateral and graft renal artery stenosis
• Current diagnosis of heart failure (New York Heart Association Class II-IV)
• Patients taking any of the following concomitant medications following screening: Renin-angiotensin receptor(RAAS) blockers other than study drug, Lithium, potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels, Non-steroidal anti-inflammatory drugs (NSAIDS), including selective COX-2 inhibitors, acetylsalicylic acid >3g/day, and non-selective NSAIDs, Antidepressant drugs in the class of Monoamine oxidase (MAO) inhibitors (e.g. phenelzine), Chronic use of stimulant therapy for Attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD) -Patients who demonstrate clinically significant ECG abnormalities such as concurrent potentially life threatening arrhythmia or symptomatic arrhythmia and patients with second or third degree heart block without a pacemaker.
• Coarctation of the aorta with a gradient of >=30 mmHg
• Previous solid organ transplantation except renal transplantation.
• Patients known to be positive for the human immunodeficiency virus (HIV)
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drug
• Known or suspected contraindications to the study drug, including severe hepatic impairment, biliary cirrhosis, cholestasis and history of allergy to ARBs and/or angiotensin-converting enzymes (ACE) and/or Direct Renin Inhibitors (DRIs)
• History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
• History or evidence of drug or alcohol abuse within the last 12 months.
• Female patients of child-bearing potential, defined as all female patients physiologically capable of becoming pregnant, unless they are willing to use highly effective contraception during the study
• Pregnant or nursing (lactating) female patients
• Participation in any investigational drug study within 30 days prior to screening or within 5 elimination half-lives of the study drug prior to screening, or whichever is longer.
• History of hypersensitivity to the study drug or to drugs of similar chemical classes.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: valsartan; Valsartan starting dose: ≥18 kg to <35 kg is 40 mg, ≥35 kg to <80 kg is 80 mg, ≥80 kg to ≤160 kg is 160 mg for 1 week then Valsartan maintenance dose: ≥18 kg to <35 kg is 80 mg, ≥35 kg to <80 kg is 160 mg, ≥80 kg to ≤160 kg is 320 mg after Week 8 if the Mean Sitting Systolic Blood Pressure (MSSBP) and/or Mean Sitting Diastolic Blood Pressure (MSDBP) was higher than 95th percentile for age, gender and height under the maintenance valsartan dose then add amlodipine and/or Hydrochlorothiazide (HCTZ). The valsartan +antihypertensive group includes patients who received background antihypertensive medication or received antihypertensive medication including amlodipine or HCTZ during the study.

Drug: Valsartan; week 1: 40/80/160 week 2-78: 80/160/320mg, oral, by mouth, once daily; Other Names: VAL489; Drug: amlodipine; added to valsartan after week 8 if the MSSBP and/or MSDBP was higher than 95th percentile for age, gender and height under the maintenance valsartan dose; Drug: Hydrochlorothiazide; added to valsartan after week 8 if the MSSBP and/or MSDBP was higher than 95th percentile for age, gender and height under the maintenance valsartan dose; Other Names: HCTZ

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 End Point (Week 78 or Last Observation Carried Forward (LOCF)	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 Point (Week 78 or Last observation carried forward (LOCF)
Change From Baseline in Mean Sitting Diastolic Blood Pressure (MsDBP) at End Point (Week 78 or Last Observation Carried Forward (LOCF)	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 Point (Week 78 or Last observation carried forward (LOCF)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With MSSBP, MSDBP and (MSSBP and MSDBP Combined) < 95th Percentile for Gender, Age, and Height	Number of Participants with Mean sitting systolic (MSSBP) and mean sitting diastolic(MSDBP) blood pressure and both combined less than the 95th percentile for age, gender and height	End Point (Week 78 or Last observation carried forward (LOCF)
Percentage of Chronic Kidney Disease (CKD) Patients Who Had >=50% Reduction in Urine Albumin/Creatinine Ratio (UACR) From Baseline to End Point	Percentage of Patients with CKD who had Urine albumin creatinine reduction >/= 50% from baseline	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)
Percentage of Chronic Kidney Disease (CKD) Patients Who Had Estimated Glomerular Filtration Rate (eGFR) Decrease > 25 % From Baselinefrom Baseline to End Point	Percentage of Patients with CKD who had eGFR decrease > 25 % from Baseline	Baseline, End Point (Week 78 or Last observation carried forward (LOCF)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: May 9, 2011
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (Estimate): June 3, 2011

Study Record Updates

• Last Update Posted (Estimate): July 13, 2016
• Last Update Submitted That Met QC Criteria: June 13, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Hypertension, pediatric; Hypertension with or without chronic kidney disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Renal Insufficiency; Hypertension; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Valsartan; Hydrochlorothiazide
• Other Study ID Numbers: CVAL489K2305; 2009-017594-37 (EudraCT Number)