Atacand Dose Ranging in Hypertensive Pediatric Subjects 1 Year to Less Than 6 Years of Age

A Dose-ranging Safety and Pharmacokinetics Study of Candesartan Cilexetil in Hypertensive Pediatric Subjects 1 to Less That 6 Years of Age: A 4-week, Multicenter, Randomized, Double-blind Study With a 1-year, Open-label, Follow-up Period.

This is a dose ranging study of candesartan cilexetil in hypertensive pediatric subjects ages 1 to less than 6 years of age. It employs a double blind, randomized, dose ranging design intended for conduct as a multicenter trial. There are 3 study 'periods': a 1-week placebo run-in, a 4-week double blind treatment, and a 52-week open-label, long-term treatment period. 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 (0.05 mg/kg, or 0.20 mg /kg or 0.40 mg /kg), liquid formulation, in a 1:1:1 ratio for 4-weeks. At the end of randomized dose allocation (Day 28), blood pressure assessment will be performed and subjects may begin the 52-week, open-label treatment period of the study.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: candesartan cilexetil (Atacand); Drug: candesartan cilexetil (Atacand); Drug: candesartan cilexetil (Atacand)

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium
    • Research Site
  • Gent, Belgium
    • Research Site
• Denmark
  • Arhus, Denmark
    • Research Site
• France
  • Strasbourg Cedex, France
    • Research Site
• Germany
  • Berlin, Germany
    • Research Site
  • Erlangen, Germany
    • Research Site
  • Hamburg, Germany
    • Research Site
  • Heidelberg, Germany
    • Research Site
  • Marburg, Germany
    • Research Site
  • Rostock, Germany
    • Research Site
• Italy
  • Genova, Italy
    • Research Site
  • Milano, Italy
    • Research Site
  • Padova, Italy
    • Research Site
  • Roma, Italy
    • Research Site
• Poland
  • Gdansk, Poland
    • Research Site
  • Kraków, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
• Puerto Rico
  • San Juan, Puerto Rico
    • Research Site
• Ukraine
  • Crimea, Ukraine
    • Research Site
  • Kyiv, Ukraine
    • Research Site
• United Kingdom
  • London, United Kingdom
    • Research Site
  • Manchester, United Kingdom
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States
      • Research Site
  • California
    • Los Angeles, California, United States
      • Research Site
    • San Francisco, California, United States
      • Research Site
  • Florida
    • Miami, Florida, United States
      • Research Site
    • Orlando, Florida, United States
      • Research Site
  • Idaho
    • Boise, Idaho, United States
      • Research Site
  • Michigan
    • Detroit, Michigan, United States
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States
      • Research Site
  • Oregon
    • Portland, Oregon, United States
      • Research Site
  • Pennsylvania
    • Malvern, Pennsylvania, United States
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States
      • Research Site
  • Texas
    • Beaumont, Texas, United States
      • Research Site
    • Houston, Texas, United States
      • Research Site
    • San Antonio, Texas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent by a parent or a legal guardian.
• Weight > 10 kg and < 40 kg.
• SiSBP and/or SiDBP > 95th percentile and < 20 mm Hg (systolic) and/or 10 mm Hg (diastolic) above the 95th percentile at screening and at randomization based on height-adjusted charts for age and gender.

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.
• Weight < 10 kg and > 40 kg.
• Less than 80% compliance with study medication during single-blind placebo screening as assessed by residual medication volume.
• Hypertension secondary to pheochromocytoma, hyperthyroidism, or Cushing's Syndrome.
• Uncorrected coarctation of the aorta, bilateral renal artery renal artery stenosis in a single kidney.
• Estimated glomerular filtration rate (GFR) < 50 mL/min/1.73m 2 based on the Schwartz Formula (Schwartz et al, 1987).
• Renal transplant < 6 months prior to study entry. Subjects who have received a renal transplant > 6 months prior to study entry may participate in the study if: 1) renal function is stable, 2) estimated GFR >50 mL/min/1.73m 2, 3) stable doses of immunosuppressive medications are anticipated throughout the 4-week, double-blind period of the study, 4) no episodes of acute allograft rejection have occurred within 30 days of study entry, and 5) the renal allograft has no documented renal artery stenosis.

Nephrotic syndrome not in remission.

• Unstable 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.
• 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 aspartate aminotransferase (AST) or alanine aminotransferase (ALT).
• Known hypersensitivity to ARBs.
• Currently receiving an angiotensin receptor blocker or an angiotensin converting enzyme inhibitor that in the investigator's judgment cannot safely be withdrawn during the study.
• Subjects receiving an angiotensin receptor blocker or an angiotensin converting enzyme inhibitor may be eligible if they undergo withdrawal of the antihypertensive medication over a 2-week washout period and subsequently meet BP inclusion/exclusion criteria.
• Subjects currently receiving other classes of antihypertensive medications (eg, diuretics, calcium channel blockers or beta-blockers) and whose BP values meet inclusion/exclusion criteria may participate in the study while continuing their current antihypertensive medication regimen. Up to 2 concomitant antihypertensive medications are permitted. Doses and dose regimens of concomitant antihypertensive medications must remain unchanged during the 4-week double-blind period of the study.
• 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 suspension.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 0.05 mg/kg Atacand oral liquid dose	Drug: candesartan cilexetil (Atacand); 0.05 mg/kg once daily oral liquid dose; Other Names: Atacand; Drug: candesartan cilexetil (Atacand); 0.20 mg/kg once daily oral liquid dose; Other Names: ATACAND; Drug: candesartan cilexetil (Atacand); 0.40 mg/kg once daily oral liquid dose; Other Names: ATACAND
Experimental: 2; 0.20 mg /kg Atacand oral liquid dose	Drug: candesartan cilexetil (Atacand); 0.05 mg/kg once daily oral liquid dose; Other Names: Atacand; Drug: candesartan cilexetil (Atacand); 0.20 mg/kg once daily oral liquid dose; Other Names: ATACAND; Drug: candesartan cilexetil (Atacand); 0.40 mg/kg once daily oral liquid dose; Other Names: ATACAND
Experimental: 3; 0.40 mg /kg Atacand oral liquid dose	Drug: candesartan cilexetil (Atacand); 0.05 mg/kg once daily oral liquid dose; Other Names: Atacand; Drug: candesartan cilexetil (Atacand); 0.20 mg/kg once daily oral liquid dose; Other Names: ATACAND; Drug: candesartan cilexetil (Atacand); 0.40 mg/kg once daily oral liquid dose; Other Names: ATACAND

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Change From Baseline to Week 4 in Systolic Blood Pressure (SBP)	From randomisation to end of double-blind treatment (4 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Change From Baseline to Week 4 in Diastolic Blood Pressure (DBP)	From randomisation to end of double-blind treatment (4 weeks)
Change in Albumin/Creatinine (A/C) Ratio for Each Assigned Dose Level From Baseline to Day 28	From randomisation to day 28
Change in Protein/Creatinine (P/C) Ratio for Each Assigned Dose Level From Baseline to Day 28	From randomisation to day 28

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Schaefer F, van de Walle J, Zurowska A, Gimpel C, van Hoeck K, Drozdz D, Montini G, Bagdasorova IV, Sorof J, Sugg J, Teng R, Hainer JW; Candesartan in Children with Hypertension Investigators. Efficacy, safety and pharmacokinetics of candesartan cilexetil in hypertensive children from 1 to less than 6 years of age. J Hypertens. 2010 May;28(5):1083-90. doi: 10.1097/HJH.0b013e328336b86b.

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: October 25, 2005
• First Submitted That Met QC Criteria: October 25, 2005
• First Posted (Estimate): October 27, 2005

Study Record Updates

• Last Update Posted (Estimate): August 31, 2011
• Last Update Submitted That Met QC Criteria: August 29, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Pediatric hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Candesartan; Candesartan cilexetil
• Other Study ID Numbers: D2451C00002; 328