Atacand Dose Range Finding Study in Pediatric Subjects 6 to <17 Years of Age

Study Overview
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Brief Summary
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Study 261A is a dose-ranging and safety study of candesartan cilexetil. It is a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group study with a 4 week treatment period in hypertensive pediatric subjects. 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 or placebo. The study includes 2 panels based on subject weight. The primary efficacy analysis is based on the intent-to-treat population and tests for slope = 0 in a linear regression model with change in sitting systolic blood pressure as the dependent and non-zero dose pooled across weight panels as the independent variable. For subjects without a Double-Blind Week 4 blood pressure determination, carrying the last value forward assigns the value. Additional analyses will include data pooled from a similar dose ranging study conducted in children 1 to < 6 years of age.

Official Title
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A Dose-Ranging and Safety Study of Candesartan Cilexetil in Hypertensive Pediatric Subjects 6 to <17 Years of Age: A 4-Week, Multinational, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study

Conditions
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Pediatric Hypertension

Intervention / Treatment
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* Drug: candsartan cilexetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ages 6 to < 17 years-of-age after parent or guardian's signing of informed consent. Subjects with hypertension that is either: Diagnosed and untreated with a mean sitting systolic and/or diastolic blood pressure ≥ 95th percentile and ≤ 20 mm Hg (systolic) and/or 10 mm Hg (diastolic) above the 95th percentile at randomisation based on height-adjusted charts for age and gender; or Previously diagnosed and currently treated with mean sitting systolic blood pressure and/or diastolic blood pressure ≥ 95th percentile and ≤ 20 mm Hg (systolic) and/or 10 mm Hg (diastolic) above the 95th percentile at randomisation (off treatment) based on height-adjusted charts for age and gender. Females of childbearing potential (post-menarche) must have a negative urine pregnancy test prior to randomization and adhere to a pregnancy prevention method (abstinence, barrier method plus spermicidal foam, oral, or implanted contraceptive). A signed informed consent by a parent or a legal guardian and an assent form signed by the subject (if applicable). 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. Hypertension secondary to coarctation of the aorta, pheochromocytoma, hyperthyroidism, Cushing's syndrome, or medications (eg: corticosteroids). Known history of bilateral renal artery stenosis, unilateral renal artery stenosis or a renal transplant. Glomerular filtration rate < 50 mL/min based on an estimated value using the Schwartz Formula. Nephrotic syndrome not in remission. 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. Pregnant or breast-feeding an infant. 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 AST or ALT. Known hypersensitivity to ARBs. Unable to be off antihypertensive medication (diuretics, beta blockers, ACE Inhibitors, etc) for 6-weeks. Inability to discontinue medications which may contribute to elevated blood pressure e.g. systemic corticosteroids. 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 tablets. Received an investigational agent within 30 days prior to receiving study medication. Alcohol or drug abuse.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: candsartan cilexetil|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough sitting systolic blood pressure, the measure of effect is change from baseline to double-blind Week 4. |  |  | 
| The endpoint (outcome variable) is the slope by linear regression |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To further evaluate the antihypertensive effects and the safety of candesartan cilexetil in hypertensive pediatric subjects. |  |  | 
| Determine the slope of the change from baseline to double-blind treatment in: |  |  | 
| • trough sitting diastolic blood pressure, |  |  | 
| • trough standing diastolic blood pressure and standing systolic blood pressure, |  |  | 
| • trough sitting pulse pressure. |  |  | 
| - Mean change from baseline in SiSBP, SiDBP, pulse pressure, and standing SBP and DBP relative to placebo for each dose group and for all dose groups pooled |  |  | 
| - Safety as assessed by adverse events, adverse events that necessitate study drug discontinuation, SAEs, heart rate, electrocardiographic findings, physical exam findings, and laboratory tests. |  |  |