Atacand Dose Ranging in Hypertensive Pediatric Subjects 1 Year to Less Than 6 Years of Age
Condition: Hypertension
MeSH terms: Hypertension
Intervention: candesartan cilexetil (Atacand); candesartan cilexetil (Atacand); candesartan cilexetil (Atacand)
Intervention description: 0.05 mg/kg once daily oral liquid dose; 0.20 mg/kg once daily oral liquid dose; 0.40 mg/kg once daily oral liquid dose
Intervention MeSH terms: Candesartan; Candesartan cilexetil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 95.0
Sex: All
Minimum age: 1 Year
Maximum age: 6 Years
Healthy volunteers: No
Keywords: Pediatric hypertension

Summary:

      This is a dose ranging study of candesartan cilexetil in hypertensive pediatric subjects ages
      1 to less than 6 years of age. It employs a double blind, randomized, dose ranging design
      intended for conduct as a multicenter trial. There are 3 study 'periods': a 1-week placebo
      run-in, a 4-week double blind treatment, and a 52-week open-label, long-term treatment
      period. Subjects undergo a screening evaluation, then a 1-week single-blind, placebo run-in,
      after which eligible subjects are allocated to receive 1 of 3 dose levels of candesartan
      cilexetil (0.05 mg/kg, or 0.20 mg /kg or 0.40 mg /kg), liquid formulation, in a 1:1:1 ratio
      for 4-weeks. At the end of randomized dose allocation (Day 28), blood pressure assessment
      will be performed and subjects may begin the 52-week, open-label treatment period of the
      study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent by a parent or a legal guardian.

          -  Weight > 10 kg and < 40 kg.

          -  SiSBP and/or SiDBP > 95th percentile and < 20 mm Hg (systolic) and/or 10 mm Hg
             (diastolic) above the 95th percentile at screening and at randomization based on
             height-adjusted charts for age and gender.

        Exclusion Criteria:

          -  Any situation, clinical condition or laboratory abnormality that, in the opinion of
             the investigator or sponsor, may interfere with the subject's participation in the
             study or would pose a significant risk to the subject or interfere with the assessment
             of safety and efficacy endpoints.

          -  Weight < 10 kg and > 40 kg.

          -  Less than 80% compliance with study medication during single-blind placebo screening
             as assessed by residual medication volume.

          -  Hypertension secondary to pheochromocytoma, hyperthyroidism, or Cushing's Syndrome.

          -  Uncorrected coarctation of the aorta, bilateral renal artery renal artery stenosis in
             a single kidney.

          -  Estimated glomerular filtration rate (GFR) < 50 mL/min/1.73m 2 based on the Schwartz
             Formula (Schwartz et al, 1987).

          -  Renal transplant < 6 months prior to study entry. Subjects who have received a renal
             transplant > 6 months prior to study entry may participate in the study if: 1) renal
             function is stable, 2) estimated GFR >50 mL/min/1.73m 2, 3) stable doses of
             immunosuppressive medications are anticipated throughout the 4-week, double-blind
             period of the study, 4) no episodes of acute allograft rejection have occurred within
             30 days of study entry, and 5) the renal allograft has no documented renal artery
             stenosis.

        Nephrotic syndrome not in remission.

          -  Unstable insulin dependent diabetes mellitus.

          -  Known bleeding, coagulation, or platelet disorder that could interfere with blood
             sampling.

          -  Clinically significant valvular heart disease.

          -  Clinical diagnosis of heart failure.

          -  Clinically significant arrhythmia (eg, any arrhythmia requiring medical therapy or
             that causes symptoms).

          -  Second or third degree AV block.

          -  Impaired liver function defined as either acute liver disease or chronic liver disease
             with persistent liver enzyme values greater than 1½ times the upper limit of the
             reference range for aspartate aminotransferase (AST) or alanine aminotransferase
             (ALT).

          -  Known hypersensitivity to ARBs.

          -  Currently receiving an angiotensin receptor blocker or an angiotensin converting
             enzyme inhibitor that in the investigator's judgment cannot safely be withdrawn during
             the study.

          -  Subjects receiving an angiotensin receptor blocker or an angiotensin converting enzyme
             inhibitor may be eligible if they undergo withdrawal of the antihypertensive
             medication over a 2-week washout period and subsequently meet BP inclusion/exclusion
             criteria.

          -  Subjects currently receiving other classes of antihypertensive medications (eg,
             diuretics, calcium channel blockers or beta-blockers) and whose BP values meet
             inclusion/exclusion criteria may participate in the study while continuing their
             current antihypertensive medication regimen. Up to 2 concomitant antihypertensive
             medications are permitted. Doses and dose regimens of concomitant antihypertensive
             medications must remain unchanged during the 4-week double-blind period of the study.

          -  Currently using, or used within 14 days prior to receiving double-blind medication,
             any concomitant medications which in the opinion of the investigator could negatively
             affect the subject.

          -  Unable or unwilling to comply with the study requirements including blood sampling and
             swallowing study drug suspension.