Clinical trial NCT00244634: Atacand Dose Range Finding Study in Pediatric Subjects 6 to <17 Years of Age
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pediatric Hypertension
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2005-10-27
Enrollment: 238
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Trough sitting systolic blood pressure, the measure of effect is change from baseline to double-blind Week 4.
measure: The endpoint (outcome variable) is the slope by linear regression
Secondary outcomes:
measure: To further evaluate the antihypertensive effects and the safety of candesartan cilexetil in hypertensive pediatric subjects.
measure: Determine the slope of the change from baseline to double-blind treatment in:
measure: • trough sitting diastolic blood pressure,
measure: • trough standing diastolic blood pressure and standing systolic blood pressure,
measure: • trough sitting pulse pressure.
measure: - 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
measure: - Safety as assessed by adverse events, adverse events that necessitate study drug discontinuation, SAEs, heart rate, electrocardiographic findings, physical exam findings, and laboratory tests.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Madera
country: United States
facility: Research Site
state: California
city: Yuba City
country: United States
facility: Research Site
state: California
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Wilmington
country: United States
facility: Research Site
state: Delaware
city: Miami
country: United States
facility: Research Site
state: Florida
city: Athens
country: United States
facility: Research Site
state: Georgia
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Park Ridge
country: United States
facility: Research Site
state: Illinois
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Jackson
country: United States
facility: Research Site
state: Mississippi
city: Port Gibson
country: United States
facility: Research Site
state: Mississippi
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Paterson
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Beaumont
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Charleston
country: United States
facility: Research Site
state: West Virginia
city: Gent
country: Belgium
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Martin
country: Slovakia
facility: Research Site
city: Myjava
country: Slovakia
facility: Research Site
city: Trnava
country: Slovakia
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Atacand Medical Science Director, MD
role: STUDY_DIRECTOR
References: