Atacand Dose Ranging in Hypertensive Pediatric Subjects 1 Year to Less Than 6 Years of Age
Information source: AstraZeneca
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
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
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)
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.
- 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.
- 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
Nephrotic syndrome not in remission.
- Unstable insulin dependent diabetes mellitus.
- Known bleeding, coagulation, or platelet disorder that could interfere with blood
- 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
- 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
- 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
- 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.
Locations and Contacts
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