Pediatric Hypertension
Conditions
Brief summary
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.
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| • trough sitting diastolic blood pressure, | — |
| • trough standing diastolic blood pressure and standing systolic blood pressure, | — |
| To further evaluate the antihypertensive effects and the safety of candesartan cilexetil in hypertensive pediatric subjects. | — |
| - 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. | — |
| • trough sitting pulse pressure. | — |
| Determine the slope of the change from baseline to double-blind treatment in: | — |
Countries
Belgium, Hungary, Slovakia, United States
Outcome results
None listed