Safety and Tolerability of Valsartan in Children 6 to 17 Years of Age
Condition: Hypertension; Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hypertension
Intervention: Valsartan; amlodipine; Hydrochlorothiazide
Intervention description: week 1: 40/80/160 week 2-78: 80/160/320mg, oral, by mouth, once daily; 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; 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
Intervention MeSH terms: Amlodipine; Valsartan; Hydrochlorothiazide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 150.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Hypertension, pediatric; Hypertension with or without chronic kidney disease

Summary:

      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.
    

Eligibility criteria:

        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