Atacand Dose Ranging in Hypertensive Pediatric Subjects 1 Year to Less Than 6 Years of Age

Condition(s) targeted: Hypertension

Intervention: candesartan cilexetil (Atacand) (Drug); candesartan cilexetil (Atacand) (Drug); candesartan cilexetil (Atacand) (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
AstraZeneca Atacand Medical Science Director, MD, Study Director, Affiliation: AstraZeneca

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.

Official title: A Dose-Ranging Safety and Pharmacokinetics Study of Candesartan Cilexetil in Hypertensive Pediatric Subjects 1 to Less That 6 Years of Age: A 4-Week, Multicenter, Randomized, Double-Blind Study With a 1-Year, Open-Label, Follow-up Period.

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Characterize the dose response relationship of candesartan cilexetil in hypertensive pediatric subjects (1 to <6 years of age) by evaluation of the slope of the linear regression for the change in trough sitting systolic blood pressure (SiSBP)

Secondary outcome:

Evaluate the antihypertensive effects and the safety of candesartan cilexetil in hypertensive pediatric subjects by determining the dose response relationship of candesartan cilexetil for the change in sitting and supine diastolic and systolic BP

The mean change in urinary protein/creatinine and albumin/creatinine ratio

Safety as assessed by adverse events, adverse events that necessitate study drug discontinuation, serious adverse events, physical exam findings, growth, and laboratory tests

Minimum age: 1 Year. Maximum age: 6 Years. Gender(s): Both.

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.

Research Site, Edegem, Belgium

Research Site, Gent, Belgium

Research Site, Arhus, Denmark

Research Site, STRASBOURG CEDEX, France

Research Site, Berlin, Germany

Research Site, ERLANGEN, Germany

Research Site, Hamburg, Germany

Research Site, Heidelberg, Germany

Research Site, Marburg, Germany

Research Site, ROSTOCK, Germany

Research Site, GENOVA, Italy

Research Site, MILANO, Italy

Research Site, PADOVA, Italy

Research Site, ROMA, Italy

Research Site, GDANSK, Poland

Research Site, KRAKÓW, Poland

Research Site, WARSZAWA, Poland

Research Site, San Juan, Puerto Rico

Research Site, CRIMEA, Ukraine

Research Site, KYIV, Ukraine

Research Site, LONDON, United Kingdom

Research Site, MANCHESTER, United Kingdom

Research Site, Birmingham, Alabama, United States

Research Site, Little Rock, Arkansas, United States

Research Site, Los Angeles, California, United States

Research Site, San Francisco, California, United States

Research Site, Miami, Florida, United States

Research Site, Orlando, Florida, United States

Research Site, Boise, Idaho, United States

Research Site, Detroit, Michigan, United States

Research Site, Durham, North Carolina, United States

Research Site, Cleveland, Ohio, United States

Research Site, Portland, Oregon, United States

Research Site, Malvern, Pennsylvania, United States

Research Site, Chattanooga, Tennessee, United States

Research Site, Beaumont, Texas, United States

Research Site, Houston, Texas, United States

Research Site, San Antonio, Texas, United States

Starting date: November 2004
Ending date: November 2008
Last updated: February 2, 2008