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

NCT00244621 | Completed Phase 3 Results

• 2 other identifiers: D2451C00002328
• Study Type: interventional
• Target: 95
• Locations: 10 countries
• Sites: 38

Brief Summary

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.

Conditions

Hypertension

Keywords

Pediatric hypertension

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline to Week 4 in Systolic Blood Pressure (SBP)

  From randomisation to end of double-blind treatment (4 weeks)

Secondary Outcomes (3)

• 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

Study Arms (3)

1

EXPERIMENTAL

0.05 mg/kg Atacand oral liquid dose

Drug: candesartan cilexetil (Atacand)

2

EXPERIMENTAL

0.20 mg /kg Atacand oral liquid dose

Drug: candesartan cilexetil (Atacand)

3

EXPERIMENTAL

0.40 mg /kg Atacand oral liquid dose

Drug: candesartan cilexetil (Atacand)

Interventions

candesartan cilexetil (Atacand) DRUG

0.05 mg/kg once daily oral liquid dose

Also known as: Atacand

1

Eligibility Criteria

• Age: 1 Year - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (38)

Research Site

Birmingham, Alabama, United States

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Little Rock, Arkansas, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Boise, Idaho, United States

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Detroit, Michigan, United States

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Durham, North Carolina, United States

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Cleveland, Ohio, United States

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Portland, Oregon, United States

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Malvern, Pennsylvania, United States

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Chattanooga, Tennessee, United States

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Beaumont, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Edegem, Belgium

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Ghent, Belgium

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Aarhus, Denmark

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Strasbourg, France

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Berlin, Germany

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Erlangen, Germany

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Hamburg, Germany

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Heidelberg, Germany

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Marburg, Germany

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Rostock, Germany

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Genova, Italy

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Milan, Italy

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Padua, Italy

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Roma, Italy

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Gdansk, Poland

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Krakow, Poland

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Warsaw, Poland

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San Juan, Puerto Rico

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Crimea, Ukraine

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Kyiv, Ukraine

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London, United Kingdom

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Manchester, United Kingdom

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Related Publications (1)

• 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.

  PMID: 20160654 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

candesartan cilexetil

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Gerard Lynch
• Organization: AstraZeneca

aztrial_results_posting@astrazeneca.com

Study Officials

• AstraZeneca Atacand Medical Science Director, MD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2005
• First Posted: October 27, 2005
• Study Start: November 1, 2004
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: August 31, 2011
• Results First Posted: September 15, 2009

Record last verified: 2011-08

Locations

DE (6); IT (4); US (16); DK (1); GB (2); BE (2); FR (1); PR (1); PL (3); UA (2)