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

Novartis

Status and phase: Completed; Phase 3

Conditions: Chronic Kidney Disease; Hypertension

Treatments: Drug: Hydrochlorothiazide; Drug: Valsartan; Drug: amlodipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01365481

CVAL489K2305

2009-017594-37 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 150 patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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150 participants in 1 patient group

valsartan

Experimental group

Description:

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.

Treatment:

Drug: amlodipine

Drug: Valsartan

Drug: Hydrochlorothiazide