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

Pediatric Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00244634
• Other study ID #: D2451C00261
• Secondary ID: 261A
• Status: Completed
• Phase: Phase 3
• First received: October 25, 2005
• Last updated: December 17, 2007
• Start date: September 2003
• Est. completion date: November 2005

Study information

• Verified date: December 2007
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pediatric Hypertension

Intervention

Drug:
• candsartan cilexetil

Locations

Country	Name	City	State
Belgium	Research Site	Gent
Hungary	Research Site	Budapest
Hungary	Research Site	Miskolc
Hungary	Research Site	Szeged
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Martin
Slovakia	Research Site	Myjava
Slovakia	Research Site	Trnava
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Athens	Georgia
United States	Research Site	Augusta	Georgia
United States	Research Site	Beaumont	Texas
United States	Research Site	Beverly Hills	California
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charleston	West Virginia
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Houston	Texas
United States	Research Site	Jackson	Mississippi
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madera	California
United States	Research Site	Miami	Florida
United States	Research Site	New Hyde Park	New York
United States	Research Site	Newark	Delaware
United States	Research Site	Norfolk	Virginia
United States	Research Site	Park Ridge	Illinois
United States	Research Site	Paterson	New Jersey
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Port Gibson	Mississippi
United States	Research Site	Portland	Oregon
United States	Research Site	Salt Lake City	Utah
United States	Research Site	St. Louis	Missouri
United States	Research Site	Wilmington	Delaware
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Yuba City	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Belgium,  Hungary,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough sitting systolic blood pressure, the measure of effect is change from baseline to double-blind Week 4.
Primary	The endpoint (outcome variable) is the slope by linear regression
Secondary	To further evaluate the antihypertensive effects and the safety of candesartan cilexetil in hypertensive pediatric subjects.
Secondary	Determine the slope of the change from baseline to double-blind treatment in:
Secondary	• trough sitting diastolic blood pressure,
Secondary	• trough standing diastolic blood pressure and standing systolic blood pressure,
Secondary	• trough sitting pulse pressure.
Secondary	- 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
Secondary	- Safety as assessed by adverse events, adverse events that necessitate study drug discontinuation, SAEs, heart rate, electrocardiographic findings, physical exam findings, and laboratory tests.