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

Hypertension Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00244621
• Other study ID #: D2451C00002
• Secondary ID: 328
• Status: Completed
• Phase: Phase 3
• First received: October 25, 2005
• Last updated: August 29, 2011
• Start date: November 2004
• Est. completion date: August 2008

Study information

• Verified date: August 2011
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 6 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• candesartan cilexetil (Atacand)
0.05 mg/kg once daily oral liquid dose
• candesartan cilexetil (Atacand)
0.20 mg/kg once daily oral liquid dose
• candesartan cilexetil (Atacand)
0.40 mg/kg once daily oral liquid dose

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  France,  Germany,  Italy,  Poland,  Puerto Rico,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline to Week 4 in Systolic Blood Pressure (SBP)		From randomisation to end of double-blind treatment (4 weeks)	No
Secondary	Mean Change From Baseline to Week 4 in Diastolic Blood Pressure (DBP)		From randomisation to end of double-blind treatment (4 weeks)	No
Secondary	Change in Albumin/Creatinine (A/C) Ratio for Each Assigned Dose Level From Baseline to Day 28		From randomisation to day 28	No
Secondary	Change in Protein/Creatinine (P/C) Ratio for Each Assigned Dose Level From Baseline to Day 28		From randomisation to day 28	No