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

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00244634
First received: October 25, 2005
Last updated: December 17, 2007
Last verified: December 2007
  Purpose

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.


Condition Intervention Phase
Pediatric Hypertension
Drug: candsartan cilexetil
Phase 3

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Trough sitting systolic blood pressure, the measure of effect is change from baseline to double-blind Week 4.
  • The endpoint (outcome variable) is the slope by linear regression

Secondary Outcome Measures:
  • To further evaluate the antihypertensive effects and the safety of candesartan cilexetil in hypertensive pediatric subjects.
  • Determine the slope of the change from baseline to double-blind treatment in:
  • • trough sitting diastolic blood pressure,
  • • trough standing diastolic blood pressure and standing systolic blood pressure,
  • • trough sitting pulse pressure.
  • - 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
  • - Safety as assessed by adverse events, adverse events that necessitate study drug discontinuation, SAEs, heart rate, electrocardiographic findings, physical exam findings, and laboratory tests.

Estimated Enrollment: 238
Study Start Date: September 2003
Study Completion Date: November 2005
  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00244634

  Show 44 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: AstraZeneca Atacand Medical Science Director, MD AstraZeneca
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00244634     History of Changes
Other Study ID Numbers: D2451C00261, 261A
Study First Received: October 25, 2005
Last Updated: December 17, 2007
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Candesartan cilexetil
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014