Efficacy, Safety, & Pharmacokinetics of Candesartan Cilexetil in Hypertensive Paediatric Subjects 6 to < 17 Years of Age

Hypertension Clinical Trial

Official title:

A Multicenter, Multinational, Open-Label Study of the Efficacy, Safety, and Pharmacokinetics of Candesartan Cilexetil in Hypertensive Paediatric Subjects 6 to < 17 Years of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00244595
• Other study ID #: D2451C00001
• Secondary ID: 261B
• Status: Completed
• Phase: Phase 3
• First received: October 25, 2005
• Last updated: December 8, 2009
• Start date: September 2003
• Est. completion date: November 2006

Study information

• Verified date: December 2009
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are to describe candesartan cilexetil antihypertensive effects in terms of achieved blood pressure and hypertension control rates and the relationship between subject characteristics and antihypertensive efficacy, and between antihypertensive therapy (candesartan cilexetil dose and add-on treatments) and efficacy over a 1 year treatment period in hypertensive children ages 6 to < 17 years; to describe growth in terms of height and weight in the study population; to describe change in neurocognition as assessed by the Full Scaled IQ score in a subset of study subjects; to determine the pharmacokinetics of candesartan in hypertensive paediatric subjects ages 6 to < 17 years; and to describe safety including adverse events and adverse events necessitating study drug discontinuation including dose level and dose duration relationships and growth over a 1 year period in hypertensive children age 6 to < 17 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 235
• Est. completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

• The subjects must have fulfilled the eligibility criteria for and have participated in Study 261A or did not participate in Study 261A but meet the following criteria:

• Diagnosed and untreated hypertension, or

• Diagnosed and treated, but off antihypertensive treatment for at least 2 days with a mean sitting systolic blood pressure and/or sitting diastolic blood pressure = 95th percentile and = 20 mm Hg (systolic) and/or 10 (diastolic) mm Hg above the 95th percentile based on height-adjusted charts for age and gender.

• Females of childbearing potential (post-menarche), must have a negative urine pregnancy test and adhere to a pregnancy prevention method (abstinence, a barrier method plus a spermicidal foam or an 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 (except in Study 261A).

• Alcohol or drug abuse.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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	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	Phoenix	Arizona
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	- Achieved sitting, trough, systolic blood pressure summarized over time and at Week 52 & the mean of the last two measures.
Primary	- The measure of effect is the mean value and the corresponding descriptive statistics.
Primary	- Additional measures include mean diastolic blood pressure, and the proportion of subjects meeting 'controlled' criteria.
Secondary	- Subject and baseline characteristics, antecedent treatment (eg, in 261A, an double-blind placebo-controlled efficacy study that is described elsewhere)
Secondary	- The relationship to efficacy measures
Secondary	- The relationship of antihypertensive treatment (candesartan cilexetil dose; add on therapy) and achieved blood pressure.