Clinical trial NCT00244595: Efficacy, Safety, & Pharmacokinetics of Candesartan Cilexetil in Hypertensive Paediatric Subjects 6 to < 17 Years of Age
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Pediatric hypertension
Hypertension in children
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2005-10-27
Enrollment: 235
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: - Achieved sitting, trough, systolic blood pressure summarized over time and at Week 52 & the mean of the last two measures.
measure: - The measure of effect is the mean value and the corresponding descriptive statistics.
measure: - Additional measures include mean diastolic blood pressure, and the proportion of subjects meeting 'controlled' criteria.
Secondary outcomes:
measure: - Subject and baseline characteristics, antecedent treatment (eg, in 261A, an double-blind placebo-controlled efficacy study that is described elsewhere)
measure: - The relationship to efficacy measures
measure: - The relationship of antihypertensive treatment (candesartan cilexetil dose; add on therapy) and achieved blood pressure.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
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: Trnava
country: Slovakia
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Atacand Medical Science Director, MD
role: STUDY_DIRECTOR
References: